Poster Session 1

S. Krasnegor¹, A. Paciorek¹, K. H. Natsuhara¹, K. Kuwahara², K. Blevins³, K. Blum¹, M. Kim¹, H. S. Rugo⁴, M. Melisko¹, M. Majure¹, L. A. Huppert¹, H. Batra-Sharma¹, L. J. Esserman¹, A. Chien¹; ¹Helen Diller Family Comprehensive Cancer Center, UCSF, San Francisco, CA, ²Geisel School of Medicine, Dartmouth College, Hanover, NH, ³Anschutz School of Medicine, University of Colorado, Aurora, CO, ⁴Duarte Cancer Center, City of Hope, Duarte, CA.

Background: Hair loss is a significant quality of life issue for women with breast cancer (BC) and may be particularly distressing for young women. Scalp cooling (SC) is effective at preventing chemotherapy (CT)-induced alopecia, and studies suggest improved quality of life in patients who have undergone successful SC. However, SC is rarely covered by insurance. The decision to use SC is personal. We aimed to understand how young women navigate the decision to use SC during CT, and self-reported estimates of hair loss, hair recovery, and cost at 1-year follow-up (FU). Methods: This is a single-institution prospective registry of young women diagnosed with early BC <45 yrs of age. Patients (pts) diagnosed within 6 months were eligible for study entry. This analysis included pts who received CT. Electronic surveys were administered at baseline (BL) and 1-year FU, which included questions about SC use, efficacy, satisfaction, and cost. Anxiety and depression were assessed through validated PROMIS measures. Pearson chi-squared, Kruskal-Wallis, and linear regressions statistics were used to test for associations between SC, PROMIS scores, and pt characteristics. SC devices included Penguin, DigniCap, or other systems. Results: Between May 2018 and May 2025, 265 pts who received neo/adjuvant CT were enrolled in the Young Women’s Registry. Of the 265 pts, 202 completed BL and/or 1-year FU surveys. Median age was 38 years; 60% White, 23% Asian, 3% Black, 8% Hispanic/Latina. 45% of pts had HR+/HER2- tumors, 23% TNBC, and 32% HER2+. 14% were single, 56% had children. 143 (71%) had an annual income >$100,000, 180 (89%) held college or higher degrees. Of pts that used SC, 31% received AC-containing and 69% receivednon-AC-containing CT. Pts who received non-AC regimens were more likely to use SC (p=0.046). Of 202 pts, 106 (52%) used SC. SC use was not associated with age, income, education level, having children, relationship status, or race. Depression and anxiety were assessed at BL using PROMIS measures in 129 pts. Pts that planned to use SC had higher anxiety (p=0.046), but no association with depression scores was evident (p=0.169). 75 of 106 (71%) pts who used SC completed a 1-year FU survey. 6% of pts reported losing <10% of their hair during CT, 19% reported 10-24%, 15% reported 25-49%, 32% reported 50-74%, 22% reported 75-99%, and 6% reported losing 100% of their hair (3/5 pts had received AC). When asked about satisfaction with SC use, 26% stated they were extremely satisfied, 38% were satisfied, 22% were neutral, and 14% were dissatisfied. 79% reported they would use SC again, 21% said they would not. At 1-year FU, 43% reported that their hair was back to BL, 37% recovered most, 13% recovered some, and 7% recovered a little of their hair. No pts reported that they had not recovered any hair. Pts with less hair loss were more likely to report satisfaction with SC use (p<0.001). PROMIS Anxiety and Depression scores at 1-year FU were not associated with degree of self-reported hair loss or recovery. Pts were asked about out-of-pocket SC expenses. 15% reported spending < $1,000, 23% spent $1,000-1,999, 30% spent $2,000-2,999, 18% spent $3,000-3,999, 7% spent $4,000-4,999, and 7% spent > $5,000. There was no association between out-of-pocket expense and satisfaction with SC at 1-year FU. Conclusions: In this prospective, single institution young women’s study, 52% chose to use SC. Higher rates of BL anxiety were associated with a plan to use SC. Despite SC use, some pts reported significant hair loss, with 28% reporting loss of > 75% of their hair. At 1-year FU, the majority (68%) were satisfied with their SC experience, however hair loss, hair regrowth, and cost varied widely. SC is an important option for young pts. These data can improve shared decision-making around the use of SC. Techniques to improve efficacy are still needed.

I. Zhi¹, E. Kwag², R. Baser³, S. Li³, L. Taylor³, D. Kim³, J. Mao³, T. Bao⁴; ¹Medical Oncology and Hematology, NYU Grossman Long Island School of Medicine Perlmutter Cancer Center – Long Island, Minoela, NY, ²Integrative Medicine Service, Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, ³Integrative Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, ⁴Zakim Center for Integrative Therapies and Healthy Living, Dana-Farber Cancer Institute, Boston, MA.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) affects up to 80% of breast cancer patients treated with neurotoxic chemotherapy, with nearly 50% requiring dose reduction or discontinuation. While cryotherapy has shown promise in CIPN prevention, many patients still develop symptoms. This study evaluated the effectiveness of real versus sham acupuncture in early-stage breast cancer patients who developed CIPN despite using cryotherapy during taxane-based chemotherapy.Method: Chemotherapy included paclitaxel or nab-paclitaxel, with co-administered agents (e.g., carboplatin, pembrolizumab, trastuzumab, pertuzumab) permitted. Patients were randomized in a 1:1 to receive either real acupuncture (RA) or sham acupuncture (SA) weekly for a minimum of four sessions during chemotherapy. The primary outcome was neuropathy pain by the Neuropathic Pain Scale (NPS) after 4 weeks of intervention. Secondary outcomes included the relative dose intensity (RDI) of taxane chemotherapy, defined as the ratio of delivered dose to planned dose. Licensed acupuncturists delivered semi-standardized protocols. All continuous outcomes were analyzed using constrained linear mixed models adjusting for randomization stratification variables; binary RDI was analyzed using logistic regression.Results: Eighty female patients were enrolled (median age, 51.0 years; range, 24.0-80.9). Paclitaxel was used in 75%, nab-paclitaxel in 25%, and cryotherapy in 94.6%. Baseline characteristics were balanced. The retention rate was 28.8%. No acupuncture-related adverse events occurred. After 4 weeks, both RA and SA groups showed statistically significant NPS reductions (RA: -6.07, P = .039; SA: -6.98, P = .021), sustained at 12-week follow-up (RA: -12.68, P < .001; SA: -10.52, P 80% maintaining ≥85% RDI (P = .80). Numerically, more RA patients achieved ≥30% NPS reduction (15 vs 11), and fewer worsened (6 vs 11) than SA, though differences were not significant (P = .20).Conclusion: This is the first sham acupuncture-controlled study to evaluate the effectiveness of acupuncture in preventing CIPN progression after cryotherapy in patients with breast cancer. Both RA and SA were associated with statistically significant reductions in neuropathy pain and high chemotherapy delivery. However, the absence of significant differences between real and sham acupuncture suggests that acupuncture may not provide specific therapeutic benefits beyond placebo or attention effects. The continuous improvement observed during and after chemotherapy exceeded the typical trajectory of CIPN, suggesting potential therapeutic effects of both RA and SA warrant further investigation.

R. Matsunuma¹, S. Nakagaki², E. Nakatani³, M. Kikuchi⁴, N. Wada⁵, K. Yonezawa⁶, T. Isono⁷, R. Hayami¹, M. Kaga⁸, M. Tsuneizumi¹; ¹Breast Surgery, Shizuoka General Hospital, Shizuoka, JAPAN, ²Pharmacy, Shizuoka General Hospital, Shizuoka, JAPAN, ³Biostatistics and Health Data Science, Graduate School of Medical Science Nagoya City University, Aichi, JAPAN, ⁴Surgery, Japanese Red Cross Shizuoka Hospital, Shizuoka, JAPAN, ⁵Clinical Oncology, Tokyo Dental College Ichikawa General Hospital, Ichikawa, JAPAN, ⁶Surgery, Shizuoka City Hospital, Shizuoka, Shizuoka, JAPAN, ⁷Surgery, Shimada General Medical Center, Shimada, JAPAN, ⁸Pharmacy, Tokyo Dental College Ichikawa General Hospital, Shizuoka, JAPAN.

Background: Infusion reactions (IRs) are frequently observed adverse events associated with HER2-targeted monoclonal antibodies, particularly trastuzumab and pertuzumab. These reactions can impair treatment tolerability and necessitate prolonged observation, delay, or discontinuation of therapy. Although dexamethasone is routinely administered as premedication to mitigate docetaxel-induced hypersensitivity, the optimal timing of dexamethasone administration relative to HER2-targeted therapy remains undefined. This study aimed to evaluate whether administering dexamethasone prior to HER2-targeted agents can reduce the incidence of IRs in patients with HER2-positive early breast cancer receiving standard trastuzumab, pertuzumab, and docetaxel therapy. Methods: This randomized, open-label, multicenter trial enrolled 100 patients with HER2-positive stage I-III breast cancer across multiple institutions. Patients were randomly assigned (1:1) to receive dexamethasone either before (experimental group) or after (control group) the infusion of trastuzumab and pertuzumab during the first treatment cycle. All patients received standard chemotherapy with docetaxel (75 mg/m2), trastuzumab (8 mg/kg loading dose), and pertuzumab (840 mg loading dose). Dexamethasone was administered intravenously at 9.9 mg either immediately prior to HER2-targeted therapy or after completion, according to group assignment. The primary endpoint was the incidence of any-grade IRs during the first cycle. Secondary endpoints included the incidence of grade >=3 IRs, IRs during cycle 2, and overall treatment-related adverse events (AEs). The time of IR onset relative to dexamethasone administration was also analyzed. Results: Of the 100 patients enrolled, 50 were allocated to each group. The incidence of IRs during cycle 1 was significantly lower in the experimental group (24.0%) compared to the control group (60.0%) (p =3 IRs occurred in either group. During cycle 2, IR incidence was low and did not significantly differ between the experimental and control groups (8.0% vs. 10.2%, p = 0.703), suggesting that immune tolerance may develop after initial exposure. The frequency of treatment-related AEs, including hematologic and non-hematologic toxicities, was comparable between groups (98.0% vs. 100.0%; p > 0.999). A time-course analysis showed that most IRs in the control group occurred prior to dexamethasone administration, indicating a potential protective effect of early corticosteroid exposure. Conclusions: Premedication with dexamethasone administered prior to HER2-targeted agents significantly reduced the incidence of IRs during the first treatment cycle without introducing additional toxicity. This simple, cost-effective modification to standard premedication protocols improves the safety and tolerability of trastuzumab and pertuzumab combination therapy. Given the widespread use of monoclonal antibodies in oncology, our findings may have broader implications for optimizing premedication strategies across various therapeutic settings.

L. Mathiot¹, C. Poiraud², J. Dimet³, L. Ropers³, M. Fenot², E. Bourbouloux¹, S. Abadie-Lacourtoisie⁴, C. El Kouri⁵, V. Delecroix⁶, R. Lamy⁷, M. Noblecourt⁸, O. Cojocarasu⁹, F. Scotté¹⁰, J. Frenel¹, F. Priou¹¹; ¹Department of Medical Oncology, Institut de Cancérologie de l’Ouest, Saint-Herblain, FRANCE, ²Department of Dermatology, Centre Hospitalier Departemental Vendée, La Roche sur Yon, FRANCE, ³Clinical Research Centre, Centre Hospitalier Departemental Vendée, La Roche sur Yon, FRANCE, ⁴Department of Medical Oncology, Institut de Cancérolologie de l’Ouest, Angers, FRANCE, ⁵Department of Medical Oncology, Centre Catherine de Sienne, Nantes, FRANCE, ⁶Department of Medical Oncology, Clinique Mutualiste de l’Estuaire, Saint-Nazaire, FRANCE, ⁷Department of Medical Oncology, Centre Hospitalier Bretagne Sud, Lorient, FRANCE, ⁸Department of Medical Oncology, Centre Hospitalier de Cholet, Cholet, FRANCE, ⁹Department of Medical Oncology, Centre Hospitalier du Mans, Le Mans, FRANCE, ¹⁰Interdisciplinary Cancer Course Department, Gustave Roussy Cancer Institute, Villejuif, FRANCE, ¹¹Department of Medical Oncology, Centre Hospitalier Departemental Vendée, La Roche sur Yon, FRANCE.

Background: The use of docetaxel in the (neo)adjuvant treatment of early-stage breast cancer (eBC) is frequently linked to notable nail toxicities, which can negatively impact quality of life (QoL) and potentially lead to treatment delays. Cryotherapy, involving the use of frozen gloves and socks, is used as a strategy to decrease docetaxel-induced nail toxicity. Strong evidence supporting its efficacy at lower cumulative doses of docetaxel and its overall tolerability remains limited. Methods: BANQUISE trial was a randomized, open-label, multicenter study investigating the efficacy of cryotherapy in eBC patients receiving three cycles of (neo)adjuvant docetaxel (100 mg/m²) following three cycles of (F)EC 100. Participants were randomized after completing three cycles of (F)EC to either the cryotherapy group, with frozen gloves and socks applied 15 minutes before and removed 15 minutes after the docetaxel infusion, or to the control group. The primary endpoint was the incidence of nail toxicity grade ≥ 2 between the first dose of docetaxel and eight weeks after the last dose of docetaxel, assessed using CTCAE v4.0 criteria by investigators. Secondary endpoints included a docetaxel nail toxicity (DNT) score assessed by a blinded dermatologist at weeks 8 and 24 using photographs. This score integrates the CTCAE V4.0 grade and the number of affected fingers, assigning 1 point per digit for grade 1 toxicity and 5 points per digit for grade 2 toxicity. Cryotherapy tolerability, and patient-reported outcomes (PROs) were measured at each cycle and week 8 and 24 after last dose of docetaxel by the EORTC QLQ-C30 and BR23 questionnaires. Statistical analyses used chi-squared and t-tests, with significance set at p<0.05. Results: From January 2014 to March 2019, a total of 280 patients were randomized to either the cryotherapy arm (n=141) or the control arm (n=139). The median age was 54 years (range 27-78). The mean cumulative dose of docetaxel was 471 mg (range: 150-660 mg) in the cryotherapy arm and 467 mg (range: 176-600 mg) in the control arm. Docetaxel dose reduction was required in 28 patients (21.9%) in the cryotherapy group and 30 patients (24.6%) in the control group. Frozen gloves were worn by 119 patients (84%) during all three courses of docetaxel, by 126 patients (89%) during two courses, and by 139 patients (99%) during one course. In the intention-to-treat population, cryotherapy significantly reduced the incidence of grade ≥ 2 nail toxicity at week 8 after the final docetaxel dose (18% vs. 37%, p < 0.001), as assessed by the investigators. This decrease was observed in both hand (13% vs. 29%, p = 0.002) and foot (12% vs. 24%, p = 0.011) nail toxicities. These results were supported by evaluations from a dermatologist blinded to treatment, showing a significant reduction in the DNT score for the cryotherapy group at week 8 (29.4 [95% CI, 17 to 41.8] vs. 54.9 [95% CI, 42.7 to 67.2]; p < 0.001) and at week 24 (9.5 [95% CI, 3.1 to 22] vs. 22.8 [95% CI, 10.3 to 35.3]; p = 0.025). Severe discomfort and pain were reported by 41% and 35% of patients wearing frozen gloves, and by 43% and 42% of patients using frozen socks, respectively. PROs revealed no significant differences in quality of life between the treatment arms at weeks 8 and 24. Discussion: Cryotherapy effectively reduces the incidence and severity of nail toxicity in eBC patients receiving 3 courses of (neo)adjuvant docetaxel. Although well-tolerated overall, discomfort remains a notable limitation. These findings support cryotherapy as a scalable intervention to improve chemotherapy tolerability.

D. M. Wolf¹, H. Rugo², R. Nanda³, S. Umashankar⁴, C. Yau⁴, M. Campbell¹, R. Sayaman¹, M. Magbanua¹, L. Brown-Swigart¹, G. Hirst¹, A. Glas⁵, I-SPY Investigators, L. Huppert², F. Symmans⁶, S. Borowsky⁷, P. Pohlmann⁸, A. Clark⁹, E. Stringer-Reasor¹⁰, M. Liu¹¹, H. Han¹², H. Soliman¹², J. Chien², R. Shatsky¹³, C. Isaacs¹⁴, D. Yee¹⁵, A. DeMichele⁹, J. Perlmutter¹⁶, L. Pusztai¹⁷, Z. Quandt², R. Cohen¹⁸, L. van ‘t Veer¹, L. Esserman¹⁹, A. Basu¹⁹; ¹Laboratory Medicine, University of California, San Francisco, San Francisco, CA, ²Hellen Diller Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, ³Breast Oncology Program, University of Chicago, Chicago, CA, ⁴Department of Surgery, University of California, San Francisco, San Francisco, CA, ⁵Biomarkers and data, Quantum Leap Healthcare Collaborative, San Francisco, CA, ⁶Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, ⁷Pathology, University of California, Davis; school of medicine, Sacramento, CA, ⁸Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁹Perelman Center for Advanced Medicine, University of Pennsylvania, Philadelphia, PA, ¹⁰Hematology & Oncology, University of Alabama, Birmingham, AL, ¹¹Chief Medical Officer, Natera, San Carlos, CA, ¹²Medical Oncology, Moffit Cancer Center, Tampa, FL, ¹³Medical Oncology, University of California, San Diego, San Diego, CA, ¹⁴Medical Oncology, Georgetown University, Washington, DC, CA, ¹⁵Masonic Cancer Center, University of Minessota, Minneapolis, MN, ¹⁶Breast Cancer Patient Advocacy Core, Gemini Group, Ann Arbor, MI, ¹⁷School of Medicine, Yale University, New Haven, CT, ¹⁸Biological Sciences, University of Chicago, Chicago, IL, ¹⁹Surgery, University of California, San Francisco, San Francisco, CA.

Background Neoadjuvant immunotherapy has become standard of care for triple negative (TN) breast cancer; and I-SPY2 and other trials have shown efficacy of IO in HR+HER2-, especially in immune+ subsets. However, IO agents carry risk of immune-related toxicities, some long-term. Previously we developed Imprint, an IDE-enabled immune classifier predicting response to IO now being used in I-SPY2.2 as part of the Response Predictive Subtypes. Here we pool irAE data from 5 IO arms in I-SPY2, where both TN and HR+HER2- patients enrolled, to assess whether irAE development may be predicted by gene expression signatures in pre-treatment tumor biopsies. Long-term, the goal is to develop clinical decision support tools to help balance likelihood of response to IO with likelihood of irAE development. Methods 356 patients (206 HR+HER2- and 150 TN) across 5 IO arms (69 pembrolizumab (Pembro), 76 Pembro/SD101, 73 durvalumab/olaparib, 62 cemiplimab (Cemi), and 78 Cemi/LAG3) with irAE and pCR data were analyzed. irAEs considered included adrenal insufficiency (10%; n=36), colitis (2.3%; n=8), diabetes mellitus (0.3%; n=1), hyperthyroidism (4.2%; n=15), hypothyroidism (15%; n=53), hypophysitis (1% ; n=4), pneumotitis (5.3%; n=19), and thyroiditis (1.4%; n=5) (unresolved grade 1 or grades 2/3). 32 mostly-immune (7 immune checkpoints, 14 immune cells, 3 TcClassII, 4 chemokine/cytokine, 1 interferon, 1 TGFB, 1 ESR1/PGR, and 1 proliferation) genes/signatures were evaluated from pre-treatment mRNA from Agilent 44K arrays for 344 patients. Associations between irAEs (overall/any and individual) and signatures were assessed using logistic regression, overall and within HR+HER2-, TN, and ImPrint+/- subsets. P-values were adjusted for multiple hypothesis testing using the Benjamini-Hochberg method (significance BH p<0.05). Results 31% (109/356) patients over the 5 IO arms had at least one irAE; and some patients had 2 (7%; 24/356), 3 (2%; 7/356), or 4 irAEs (1/356) (150 irAEs were distributed over 109 patients). irAE prevalence ranged from 19% to 44% by IO arm, with the highest prevalence in dual-IO arms. Prevalence of irAEs did not differ significantly between HR+HER2- and TN (OR=1.2 [0.7-2]); nor between ImPrint- and ImPrint+ (OR=1.01 [0.6-1.7]). irAEs (any: yes/no) also did not differ between responders and non-responders (OR=1.14 [0.7-1.84]). Pneumonitis, but not other irAEs nor the composite irAE vector, significantly associated with multiple signatures. 19/32 signatures, all immune, significantly associated with pneumonitis in the population as a whole (BH p<0.05). These include higher levels of immune checkpoints (e.g., CD274 (PDL1) and PDCD1 (PD1)), cell populations (e.g., T-cells and B-cells), TcClassII (e.g., ICS5 and Module4_Immune), and chemokine/cytokine signatures (CK12, TIS, and Geparsixto); and lower levels of TGFB (all BH p<0.05). Subset analysis revealed these associations to be subtype specific, restricted to patients with ImPrint+ tumors (38%). PD1 mRNA levels predict pneumonitis in this group; with an AUC=0.84, sensitivity=67% and specificity=91%. For patients with ImPrint- tumors, there were no associations between irAEs and any tested signatures. Conclusion ~30% of patients treated with neoadjuvant IO and standard chemotherapy developed an irAE. irAEs did not associate with subtype or IO response. Pneumonitis, but no other irAE, associated with pre-treatment immune signatures. This association was observed exclusively in patients with ImPrint+ tumors, where PD1 mRNA levels predicted pneumonitis. mRNA signatures may help enable early identification and treatment of IO patients likely to develop pneumonitis.

Z. Molinari¹, N. Van Damme², J. Verbeeck², A. Laenen³, S. Han¹, M. Van Houdt¹, D. Timmerman⁴, A. Smeets⁵, I. Nevelsteen⁵, Y. Van Herck⁶, F. Derouane⁶, H. Janssen⁷, A. Baten⁷, J. Verhoeven⁷, A. Van Rompuy⁸, P. Berteloot¹, T. Van Gorp¹, T. Baert¹, F. Amant¹, E. Van Nieuwenhuysen¹, H. Wildiers⁶, P. Neven¹; ¹Department of Gynaecological Oncology, UZ Leuven, Leuven, BELGIUM, ²Oncology, Belgian Cancer Registry, Brussel, BELGIUM, ³Leuven Biostatistics and Statistical Bioinformatics Centre, KU Leuven, Leuven, BELGIUM, ⁴Department of Obstetrics & Gynaecology, UZ Leuven, Leuven, BELGIUM, ⁵Department of Surgical Oncology, UZ Leuven, Leuven, BELGIUM, ⁶Department of General Medical Oncology, UZ Leuven, Leuven, BELGIUM, ⁷Department of Radiotherapy, UZ Leuven, Leuven, BELGIUM, ⁸Department of Imaging and Pathology, UZ Leuven, Leuven, BELGIUM.

Tamoxifen use increases endometrial cancer risk in premenopausal breast cancer patients. Z. Molinari, N. Van Damme, J. Verbeeck, A. Laenen, S. Han, M. Van Houdt, D. Timmerman, A. Smeets, I. Nevelsteen, Y. Van Herck, F. Derouane, H. Janssen, A. Baten, J. Verhoeven, A.S. Van Rompuy, P. Berteloot, T. Van Gorp, T. Baert, F. Amant, E. Van Nieuwenhuysen, H. Wildiers, P. NevenBackgroundA paradigm challenging retrospective study suggested that premenopausal breast cancer (BC) patients, were 3.77 times more likely to develop endometrial cancer (ECa) when treated with tamoxifen. Given that many patients may not have been truly premenopausal, we aimed to validate these results in a similar, large-scale nationwide study.MethodsWe conducted a retrospective cohort study of all diagnoses of ECa following tamoxifen initiation for non-metastatic BC in women aged 18–53 between 2008 and 2020 in Belgium. Data were obtained from the Belgian Cancer Registry and administrative databases. Definitive menopausal status could not be verified based on these data. The primary endpoint was time to ECa diagnosis up to 31/12/2022. Continuous variables were summarized as mean or median, and categorical variables as frequencies (%). The tamoxifen and non-tamoxifen cohorts were compared by year of incidence using the Mann-Whitney U test (continuous variables) and Chi-square or Fisher’s exact test (categorical variables). Patients who did not develop ECa were censored at the date of last follow-up. A Cox proportional hazards model assessed the primary endpoint, with treatment group as the main variable and patient/tumor characteristics as covariates. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using SAS software version 9.4, with significance set at p < 0.05.ResultsWe identified 38,857 early BC patients: 15,568 patients (40%; median age 47 years; 12.9% with cardiovascular risk; 3.2% diabetic) in the non-tamoxifen group and 23,289 (60%; median age 47 years; 10.9% cardiovascular risk; 2.3% diabetic) in the tamoxifen group. Tamoxifen users were more likely to have low-grade and lobular tumors, and less likely to receive (neo)adjuvant or targeted (chemo)therapy. During follow-up, 27 ECa events occurred in the non-tamoxifen group (0.17%) and 96 in the tamoxifen group (0.41%). This translated to 0.22% and 0.51% of survivors, respectively. The difference was statistically significant (HR 2.05, CI: 1.34-3.15). After adjusting for potential confounders—diabetes, cardiovascular profile, tumor grade, pT, pN, chemotherapy, and targeted therapy—the risk remained significantly elevated in the tamoxifen group (adjusted HR 1.93, CI: 1.14-3.28; p = 0.0141). ConclusionIn this Belgian cohort, tamoxifen use in women under the age of 54 with unknown menopausal status and early-stage invasive BC was associated with statistically significant increased risk of developing ECa, independent of other risk factors.

T. Kulkarni¹, R. Nanda², H. S. Rugo³, C. C. OSullivan⁴, K. M. Kalinsky⁵, J. C. Boughey⁶, P. R. Pohlmann⁷, J. Perlmutter⁸, D. Yee⁹, A. Borowsky¹⁰, F. Symmans¹¹, N. Hylton¹², L. Van ‘t Veer¹³, C. Yau¹⁴, L. Esserman¹⁵; ¹Medicine, The University of Alabama at Birmingham, Birmingham, AL, ²Medicine, University of Chicago, Chicago, IL, ³Medicine, City of Hope National Medical Center, Duarte, CA, ⁴Medicine, Mayo Clinic Comprehensive Cancer Center, Rochester, MN, ⁵Medicine, Emory University Winship Cancer Institute, Atlanta, GA, ⁶Surgery, Mayo Clinic Comprehensive Cancer Center, Rochester, MN, ⁷Medicine, UT MDACC, Houston, TX, ⁸N/A, Gemini Group, Ann Arbor, MI, ⁹Medicine, University of Minnesota, Minneapolis, MN, ¹⁰Pathology, University of California Davis, Sacramento, CA, ¹¹Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, ¹²Radiology and Biomedical Imaging,  University of California San Francisco, San Francisco, CA, ¹³Laboratory Medicine, University of California San Francisco, San Francisco, CA, ¹⁴Surgery,  University of California San Francisco, San Francisco, CA, ¹⁵Surgery, University of California San Francisco, San Francisco, CA.

Background: Combinations of antibody-drug conjugates and immunotherapy, such as trastuzumab deruxtecan (T-DXd) and rilvegostomig (rilve), respectively, offer promising efficacy but are associated with a heightened risk of drug-induced interstitial lung disease (ILD)/pneumonitis. Early detection and management are critical for optimizing patient safety, yet there are no standard protocols for real-time evaluation. We hypothesized that vigilant monitoring would enable early detection, prevent symptoms, and minimize the chance of treatment delays while testing novel therapeutic combinations that have a potential risk of ILD. Methods: We tested the combination of T-DXd and rilve administered every 3 weeks in the I-SPY2.2 phase 2 platform trial (NCT01042379), which enrolls patients with clinical stage II/III breast cancer commencing neoadjuvant systemic therapy. Given the potential risk of overlapping pulmonary toxicity of these two agents, we added rigorous monitoring with pulmonary function tests (PFTs), six-minute walk test (6MWT), and high-resolution chest CT (HRCT) scanning pretreatment and every 6 weeks thereafter. A real-time safety workflow was implemented, with pre-specified criteria for halting treatment and escalation to the next block of treatment. All abnormal findings reported on chest CT by site radiologist were centrally reviewed in real time by the study pulmonologist (T.K.) and cases of suspected ILD were adjudicated promptly by a safety committee consisting of the pulmonologist and several medical oncologists, enabling early study drug interruption and therapeutic interventions. Toxicity data were evaluated in the first 51 patients treated with T-DXd plus rilve, and a preplanned hold was initiated until safety was ascertained by the data and safety monitoring board. Results: Safety data were evaluated in the first 51 patients receiving T-DXd plus rilve. Eight ILD events were confirmed (15.68% incidence): 5 grade 1, 2 grade 2, and 1 grade 3. One patient had an early chest CT scan because of dyspnea. All cases were identified by HRCT scans; PFTs and 6MWT did not enhance early detection and were subsequently dropped from the monitoring protocol. No patient was symptomatic for more than 24 hours. Radiographic findings resolved within 14-55 days. Patients with grade 2 & 3 ILD were treated with corticosteroids. No cases of ILD required intensive care or escalated therapy beyond steroids. Early treatment escalation to the subsequent block of therapy occurred in 3 patients; all 3 patients were subsequently able to receive appropriate therapy. At the meeting, safety data from all 100 patients treated with this combination will be reported. Conclusion: Real-time, centralized monitoring and adjudication allowed for early detection and prompt management of ILD, which both mitigated severity and supported timely therapeutic management. Among the monitoring tools studied, HRCT scanning performed every 6 weeks proved most effective for early ILD identification; PFT and 6MWT did not enhance early detection. This approach offers a potential framework for future studies assessing pulmonary safety in regimens combining agents that have a known risk for inducing ILD.

P. Matte¹, I. Hacini², P. H. Cottu¹, C. Helal¹, M. Mirabel³, F. Coussy¹, F. Lerebours⁴, E. Laas⁵, E. Romano¹, L. Djerroudi⁶, S. Hescot⁷, P. Charles⁸, B. Buecher¹, J. Pierga¹, L. Cabel¹, D. Loirat¹; ¹Medical Oncology department, Institut Curie – Institute of Women’s Cancers, Paris, FRANCE, ²Department of nuclear medicine and endocrinology,, Institut Curie – Institute of Women’s Cancers, Saint-Cloud, FRANCE, ³Department of Cardiology, Institut Mutualiste Monsouris,, Paris, FRANCE, ⁴Medical Oncology department, Institut Curie – Institute of Women’s Cancers, Saint-Cloud, FRANCE, ⁵Department of Surgery, Institut Curie – Institute of Women’s Cancers, Paris, FRANCE, ⁶Department of Diagnostic and Theranostic Medicine, Institut Curie – Institute of Women’s Cancers, Paris, FRANCE, ⁷Department of nuclear medicine and endocrinology, Institut Curie – Institute of Women’s Cancers, Saint-Cloud, FRANCE, ⁸Department of internal medicine, Institut Mutualiste Monsouris,, Paris, FRANCE.

Background: In early-stage triple-negative breast cancer (TNBC), the addition of immune checkpoint inhibitors (ICIs) such as pembrolizumab to (neo)adjuvant chemotherapy has significantly improved clinical outcomes, as demonstrated in the KEYNOTE-522 trial. This approach is now the standard of care in this population. However, the increasing use of ICIs in real-world settings raises concerns about chronic immune-related adverse events (irAEs), defined as toxicities persisting more than 12 weeks after treatment discontinuation. While chronic irAEs are well documented in melanoma and lung cancer, data remain scarce in early-stage TNBC, particularly in the curative setting. Methods: We conducted a retrospective, bicentric study (Institut Curie Paris and Saint-Cloud, France) involving patients with early-stage TNBC treated with pembrolizumab according to the KEYNOTE-522 regimen. All patients received at least one dose of neoadjuvant pembrolizumab. Chronic irAEs were assessed using CTCAE v5.0 criteria and defined as immune-related toxicities persisting beyond 12 weeks after pembrolizumab discontinuation, regardless of grade, starting from grade ≥2 (i.e., requiring medical intervention or impacting daily life). The primary endpoints were the incidence, type, duration, and management of chronic irAEs. Results: A total of 203 patients with stage II/III early TNBC were consecutively included between January 2021 and November 2023. The median age was 49 years (range: 22-74). Germline BRCA1 or BRCA2 mutations were identified in 14.8% of patients (n = 30), and 92.1% (n = 187) had invasive carcinoma of no special type. Postoperatively, 59% (n = 120) received at least one cycle of adjuvant pembrolizumab, while 41% (n = 83) did not, primarily due to limiting toxicities or the presence of residual disease. On average, patients received a total of 10 cycles of pembrolizumab (range: 1-17). The pathological complete response (pCR) rate was 70%. Chronic irAEs were reported in 36.5% of patients (n = 74). Endocrine toxicity was the most frequent, accounting for 79% (n = 58) of patients. Among these, hypothyroidism was observed in 62% (n = 36) and corticotropic insufficiency in 45% (n = 26); four patients experienced both. All endocrine events required long-term hormone replacement therapy, with no cases of functional recovery observed. Cardiac toxicity (myocarditis) was reported in 4.9% of patients (n = 10) and was managed with corticosteroids and standard cardioprotective therapies; no patient required second-line immunosuppression. Other chronic irAEs included gastrointestinal events in 2.0% (n = 4; 2 pancreatitis, 1 colitis, 1 gastritis), renal toxicity in 1.5% (n = 3; all interstitial nephritis), rheumatologic and neurologic events in 1.0% each (n = 2), pulmonary toxicity in 0.5% (n = 1; interstitial lung disease), and sicca syndrome in 1.0% (n = 2). Ten patients (4.9%) experienced multiple chronic irAEs. No deaths related to immune-mediated toxicity were observed.Conclusion: This real-world analysis reveals a high incidence of chronic irAEs among patients receiving curative-intent pembrolizumab for high-risk early-stage TNBC. These chronic irAEs can significantly impact quality of life, highlighting the urgent need for prospective studies and survivorship care planning for this growing population of breast cancer survivors. Funding: Collectif Triplettes Roses grant

F. Khan¹, M. Zafar¹, B. Singeltary²; ¹Hospice and Palliative Medicine, University at Buffalo Roswell Park Comprehensive Cancer Center, Buffalo, NY, ²Hematology and Oncology, TriHealth Good Samaritan Hospital, Cincinnati, OH.

Background: The optimal approach for treating elderly patients (age ≥70) with HER2-positive breast cancer is uncertain, especially when balancing the benefits of combination chemotherapy with HER2-targeted agents versus targeted therapy alone. Given the increased risk of treatment-related toxicities in older adults, it is crucial to understand real-world outcomes and risks associated with these regimens in this population. Methods: We conducted a retrospective, real-world cohort study using the TriNetX platform. We identified two cohorts of patients aged ≥70 years with HER2-positive breast cancer. Cohort A (n=4,178) included patients who received HER2-targeted therapy (trastuzumab or trastuzumab deruxtecan) without concurrent chemotherapy (excluding docetaxel/paclitaxel). Cohort B (n=7,607) included those treated with HER2-targeted therapy in combination with chemotherapy (docetaxel or paclitaxel). Propensity score matching was performed, yielding 3,595 patients per cohort for comparative analyses. Outcomes were assessed with Kaplan-Meier survival curves and hazard ratios (HR) for mortality and major toxicities. Results: After 1:1 propensity score matching, 3,595 patients were included in each cohort. Mortality was slightly higher in the HER2-only group (25.96%) compared to the combination group (23.91%) (HR 1.136, 95% CI: 1.036-1.247, p=0.007). Hospitalization occurred more frequently in the combination group (36.2%) compared to the HER2-only group (30.3%; HR 0.830, 95% CI: 0.749-0.919, p=0.001). Outpatient visits were more frequent in the HER2-only group (56.1% vs. 32.6%; HR 1.649, 95% CI: 1.072-2.537, p=0.016). Rates of cancer progression were similar between groups (24.6% combination vs. 23.8% HER2-only; HR 1.004, p=0.951). Cardiomyopathy was more frequent in the combination group (12.7% vs. 10.4%; HR 0.834, p=0.012), while heart failure showed a non-significant trend towards higher frequency in the combination group (15.5% vs. 13.6%; HR 0.886, p=0.060). Treatment-related toxicities were consistently higher in the combination group, including neutropenia (16.3% vs. 6.0%; HR 0.359, p<0.001), anemia (35.1% vs. 24.9%; HR 0.661, p<0.001), thrombocytopenia (12.3% vs. 10.0%; HR 0.829, p=0.010), peripheral neuropathy (32.3% vs. 16.2%; HR 0.461, p<0.001), nausea/vomiting (33.0% vs. 21.7%; HR 0.608, p<0.001), mucositis (8.2% vs. 3.9%; HR 0.485, p<0.001), and diarrhea (32.1% vs. 20.9%; HR 0.598, p<0.001). Infections such as pneumonia, as well as heart failure with reduced ejection fraction (HFrEF) and severe sepsis, were also more frequent in the combination group, although not all differences reached statistical significance.The combination therapy cohort featured more complex, multi-agent treatment pathways, with nearly all patients receiving both HER2-targeted therapy and chemotherapy either concurrently or sequentially, and a small minority lacking documented treatment sequences. The HER2-only cohort showed simple, single-agent HER2-targeted therapy pathways. Conclusions: Among elderly patients with HER2-positive breast cancer, combination chemotherapy plus HER2-targeted therapy provided a modest but statistically significant improvement in survival compared to HER2-targeted therapy alone. However, this benefit was accompanied by substantially higher rates of hematologic, cardiac, neurologic, and gastrointestinal toxicities. Importantly, the risk of cancer progression was not significantly different between regimens. These results suggest that HER2-targeted therapy alone may be a reasonable and safer alternative in select elderly patients who are frail and have significant comorbidities, offering similar cancer control with significantly less toxicity.

W. Lu¹, A. Giobbie-Hurder², A. Tanasijevic¹, S. Baedorf Kassis³, E. Diederich¹, A. J. Sahraoui¹, Y. J. Jeong⁴, I. H. Shin⁵, C. Yao⁶, X. Zhang⁶, N. Lee⁴, Y. Yao⁶, C. Bao⁷, T. Bao¹, E. Yang⁸, R. Knoerl⁹, B. E. Bierer³, J. A. Ligibel¹; ¹Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, ²Department of Data Science, Dana-Farber Cancer Institute, Boston, MA, ³The Multi-Regional Clinical Trials Center, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, ⁴Department of Surgery, Daegu Catholic University, School of Medicine, Daegu, KOREA, REPUBLIC OF, ⁵Department of Medical Statistics & Informatics, Daegu Catholic University, School of Medicine, Daegu, KOREA, REPUBLIC OF, ⁶Department of Breast Diseases, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, CHINA, ⁷Department of Acupuncture, The Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, CHINA, ⁸Osher Center for Integrative Health, Brigham and Women’s Hospital and Harvard Medical School, Brookline, MA, ⁹Health Behavior and Clinical Sciences, University of Michigan School of Nursing, Ann Arbor, MI.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common, debilitating side effect, adversely impacting quality of life (QoL) and treatment outcomes in breast cancer patients. Preventive strategies for CIPN remain limited. Acupuncture has shown promise in mitigating CIPN symptoms, but its role in prevention requires further investigation. This study evaluates acupuncture’s effectiveness in preventing CIPN in early-stage breast cancer patients through a pooled analysis of three coordinated international trials. Methods: Patients with stage I-III breast cancer, with no prior neuropathic symptoms, scheduled for taxane-based chemotherapy were randomized 1:1 to acupuncture or relaxation exercises with nature videos as the control in three parallel trials in the USA, China, and South Korea. Participants in the acupuncture group received 14 standardized sessions over 12 weeks, starting before the second chemotherapy cycle. Participants in the control group received nature video relaxation during chemotherapy infusions. Follow-up extended for an additional 12 weeks. The primary endpoint was the change in CIPN severity using EORTC CIPN-20 sensory subscale at 12 weeks. Secondary endpoints included CIPN incidence, pain intensity, and QoL at week 12 and week 24. Data were pooled and analyzed using longitudinal linear mixed-effects model, stratified by site and chemotherapy schedule (weekly vs. non-weekly). All analysis were intention to treat. Results: Of 129 patients who consented, 128 were randomized (USA: 88, China: 20, South Korea: 20) and 127 were analyzed (63 acupuncture, 64 control). Median age was 46 years (range: 30-80) in the acupuncture arm and 49 years (range: 26-77) in the control arm, with 58.2% White and 38.6% Asian. At baseline, patients reported similar CIPN-20 sensory scores between study arms [0.44 points (SE 0.77) vs. 1.29 (0.77), p=0.33]. At week 12, patients in both arms reported a statistically significant increase of mean sensory change score [7.23 (1.75), 95%CI: 3.76-10.70, p<0.0001; and 8.16 (1.67), 95%CI: 4.86-11.47, p<0.0001, respectively]. There are no statistically significant differences between the acupuncture arm vs. the control arm at week 12 and week 24 (Table). No acupuncture-related serious adverse events were observed. Conclusions: Acupuncture was safe and well-tolerated but did not significantly reduce the risk and severity of CIPN when compared to the nature video control in this pooled cohort. Secondary analyses are in progress and will be reported separately. Funding Source: The Ministry of Health & Welfare, Republic of Korea, Comprehensive and Integrative Medicine R&D project through the Korea Health Industry Development Institute (KHIDI) Grant Number: HI20C1753 Clinical Trial Registry Numbers: NCT05528263, ChiCTR2200066714, KCT0008470

Y. Zektser¹, C. Sun², W. Dale², J. Ji¹, N. V. Baclig¹, H. J. Cohen³, H. Kim², V. Katheria², C. Lee¹, M. Sedrak¹; ¹Department of Medicine, UCLA David Geffen School of Medicine, Los Angeles, CA, ²Department of Supportive Care, Beckman Research Institute of City of Hope, City of Hope, Duarte, CA, ³Department of Medicine, Duke School of Medicine, Durham, NC.

Background: Clinicians infrequently use geriatric assessment in routine care, despite its superior ability to identify at-risk older adults with early breast cancer compared to clinician-rated Karnofsky Performance Status (cKPS). Asking patients to rate their own performance status may offer a more scalable alternative, but the relationship between patient-reported KPS (pKPS) and treatment outcomes is unknown. We hypothesized that pKPS would show stronger associations with treatment outcomes than cKPS but similar associations as geriatric assessment-based frailty. Methods: The HOPE study enrolled 499 women aged >65y with stage I-III breast cancer across 16 US sites who were planned to start neo/adjuvant chemotherapy. At baseline, we obtained a geriatric assessment-based Deficit Accumulation Frailty Index (DAFI; categorized as robust [DAFI <0.2] or prefrail/frail [DAFI >0.2]). cKPS and pKPS were collected and categorized as high [KPS>=80] or low [KPS<70] based on cutoffs consistent with prior studies. Our primary endpoint was grade 3+ toxicity. Secondary endpoints included treatment modifications (dose reductions, dose delays, early discontinuation) and survival (non-breast cancer-specific survival [non-BCSS]). Kappa statistics were used to evaluate agreement between cKPS and pKPS. Adjusting for age, race/ethnicity, stage, and regimen, multivariable logistic regression was used to evaluate associations of DAFI, cKPS, and pKPS with grade 3+ toxicity and treatment modifications, while Cox proportional and Fine-Gray regression were used to evaluate relationships with non-BCSS. Results: Of the 499 participants (median age 70 [65-86]), 21% were prefrail/frail, 4% had low cKPS, and 10% had low pKPS. cKPS and pKPS correlated weakly (kappa=0.16). In the adjusted multivariable model, DAFI was strongly associated with all treatment outcomes: grade 3+ toxicity, treatment modifications, and non-BCSS (Table). cKPS was only associated with toxicity and non-BCSS. pKPS was not associated with any outcomes. Table. Multivariable Associations Between Baseline Functional Status and the Odds of Toxicity and Survival Across Distinct Measures of Function

Adjusted for age, race/ethnicity, stage, and regimen. *P-value<0.05 Conclusion: Although pKPS offers a simpler, more scalable alternative to geriatric assessment, it was not associated with treatment outcomes in this study. Geriatric assessment-derived frailty remained the most robust measure, showing consistent associations with toxicity, treatment modifications, and survival, while cKPS showed limited associations. These findings underscore the need to prioritize the implementation of geriatric assessments in routine oncology practice to improve risk stratification and guide treatment decisions for older adults with breast cancer.

K. H. Natsuhara¹, M. Vella², S. C. Behr², N. Reddy³, A. J. Chien¹, M. E. Melisko¹, M. Majure¹, G. C. Buckle¹, E. J. Walker¹, L. Al Rabadi¹, A. Ko¹, M. L. Cheng¹, A. Algazi¹, H. Batra-Sharma¹, L. N. Quintal⁴, L. A. Huppert¹, H. S. Rugo⁵; ¹Division of Hematology and Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, ²Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, ³Department of Surgery, University of California San Francisco, San Francisco, CA, ⁴Department of Clinical Pharmacy, University of California San Francisco, San Francisco, CA, ⁵Breast Medical Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA.

Background: Trastuzumab-deruxtecan (T-DXd) is approved for advanced HER2+, low, and ultra-low advanced breast cancer, and multiple other solid tumors. T-DXd carries a rare but serious risk of ILD (incidence 12-15%), requiring frequent imaging and symptom evaluation. For > grade (G) 2 ILD, guidelines recommend permanent drug discontinuation. For asymptomatic G1 ILD, drug is held with the option for rechallenge (RC) after resolution of imaging findings. Limited data exist on T-DXd related ILD imaging findings and clinical outcomes after RC in patients (pts) treated in the real-world setting. Methods: We analyzed all pts treated with T-DXd at our institution from Sept 2018-June 2024. We identified pts with radiographic evidence of ILD by chart review. Adjudication of T-DXd related ILD was by treating provider and graded via CTCAE v5. A chest radiologist conducted a blinded review of baseline and follow-up chest CTs (up to 4 mos post T-DXd) for all pts treated with T-DXd, to identify possible cases of drug-related ILD and assess imaging improvement over time. Results: Of 214 pts treated with T-DXd, 44 (21%) developed ILD (27-G1, 8-G2, 4-G3, 3-G4, 2-G5). Median (med) ILD onset was 116 days (d) after 1st dose [range (r:) 9-833]. Among pts with ILD, 37 had breast, 5 had GI, 1 had lung, and 1 had head and neck cancer, with a med age of 59 yrs (r: 36-78), med 3 prior therapy lines for advanced disease (r: 0-13); 8/44 pts (18%) had renal impairment (CrCl<60mL/min). Among pts with G1 ILD, 21/27 (78%) received steroids for a med of 49d (r: 15-149). Radiographic improvement was seen at a med of 23d (r: 9-79) for pts treated with steroids vs 66d (r: 28-82) without steroids. Of 27 pts with G1 ILD, 22 (81%) were RC with T-DXd; 4 had PD at ILD diagnosis, 1 was not RC due to persistent CT findings. Med time to RC was 42d (r: 20-236); 2 pts received intervening therapy before RC. After RC, 15 pts remained on T-DXd without recurrent ILD for a med of 95d (r: 20-365); 1 pt remained on T-DXd at data lock (6/26/25); 7 pts (32%) had recurrent ILD at a med of 47d after RC (r: 20-331; 5-G1, 2-G2). Four pts with recurrent G1 ILD were RC a 2nd time (2 dose reduced) and remained on T-DXd for a med of 152d (r: 92-370); 1 pt with recurrent G1 ILD, 3 with PD, 1 remained on T-DXd at data lock. Imaging review showed complete resolution of ILD in 4 of 27 pts with G1 ILD, partial response in 15, stable disease in 2, worsening ILD in 1, and 4 were unevaluable due to missing follow-up imaging. Med time from initial ILD diagnosis to complete or partial response was 32d (r: 9-209). All 7 pts with recurrent ILD after RC had partial imaging responses before RC. 22 pts had imaging findings consistent with possible ILD but were not diagnosed with or treated for T-DXd associated ILD. Per clinician assessment, imaging findings were attributed to PD (n=7), viral infection (n=5), aspiration/infection (n=4), radiation changes (n=2), and in 4 cases, ILD findings were not documented in the official report. These 22 pts remained on T-DXd for a med of 152d (r: 20-949) and were never clinically diagnosed or treated for ILD; 21pts stopped T-DXd for PD and 1 remained on T-DXd at data lock. Conclusions: In this real-world, single institution cohort, high rates of T-DXd RC after G1 ILD were reported with long duration of clinical benefit. After RC, low rates of low grade recurrent ILD were seen with no G5 events. Four pts with recurrent G1 ILD were RC a 2^nd time with only 1 case of recurrent G1 ILD. Most pts with G1 ILD did not have complete resolution of ILD findings on CT. By imaging review, some patients had CT findings possibly concerning for ILD; however, providers identified alternative causes—underscoring the challenge of diagnosing T-DXd related ILD. This cohort provides clinically important information on RC safety and imaging characteristics associated with T-DXd related ILD.

S. Koh¹, J. Kwon², Y. Noh³, J. Na¹, J. Kim², C. Kim⁴, D. Kang¹, J. Seo⁵, M. Ock⁵; ¹Department of Hematology and Oncology, University of Ulsan, College of Medicine, Ulsan University Hospital, Ulsan, KOREA, REPUBLIC OF, ²Department of Surgery, University of Ulsan, College of Medicine, Ulsan University Hospital, Ulsan, KOREA, REPUBLIC OF, ³Department of Radiation Oncology, University of Ulsan, College of Medicine, Ulsan University Hospital, Ulsan, KOREA, REPUBLIC OF, ⁴Department of Rehabilitation, University of Ulsan, College of Medicine, Ulsan University Hospital, Ulsan, KOREA, REPUBLIC OF, ⁵Department of Preventive Medicine, University of Ulsan, College of Medicine, Ulsan University Hospital, Ulsan, KOREA, REPUBLIC OF.

Title: Evaluating the effectiveness of post-discharge management program of breast cancer patients based on Smart Cancer Care 2.0 using patient reported outcome: a preliminary analysis of a randomized clinical trial Authors: Su-Jin Koh, MD, PhD^1*, Jin Ah Kwon^2*, Young Ju Noh³, Jihyun Na¹, Jin sung Kim², Chung Reen Kim⁴, Dong Yoon Kang, MD, PhD⁵, Jeong-Wook Seo⁵, Minsu Ock, MD, PhD^5† Affiliations:¹Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea²Department of Surgery, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea³Department of Radiation Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea⁴Department of Rehabilitation, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea⁵Department of Preventive Medicine, Ulsan University Hospital, University of Ulsan College of Medicine, Republic of Korea †Corresponding authorsMinsu Ock, MD, PhDUlsan University Hospital, University of Ulsan College of MedicineDaehagbyeongwon-ro 25, Dong-gu, Ulsan 44033, Republic of KoreaEmail: ohohoms@naver.com Funding: This study was supported by a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (HA21C0107 and HA23C0478).Evaluating the effectiveness of post-discharge management program of breast cancer patients based on Smart Cancer Care 2.0 using patient reported outcome: a preliminary analysis of a randomized clinical trial Introduction: In Korea, a “Smart Cancer Care” platform that utilizes patient reported outcomes has been developed to manage treatment side effects of cancer patients and resolve various unmet needs. In this study, we applied a cancer patient post-discharge management program based on Smart Cancer Care 2.0 to breast cancer patients and evaluated its effectiveness.Methods: Breast cancer patients receiving various treatments such as surgery, radiation therapy, and chemotherapy were randomly assigned to a group that received a cancer patient post-discharge management program (group A) and a group that did not (group B). The cancer patient post-discharge management program monitored and managed various treatment side effects that cancer patients may experience, and even provided information on cancer rehabilitation and health behavior improvement. After applying the program in group A for 3 months, breast cancer patients in both groups were followed up for up to 6 months to evaluate and compare health-related quality of life, unexpected visits to medical institutions, etc.Results: As of December 2023, a total of 190 breast cancer patients were registered, and 169 breast cancer patients were preliminary analyzed in this study. As a result of comparing health-related quality of life measured by the EORTC QLQ-C30, no difference in average scores between groups A and B was confirmed at 1 month (Group A: 65.4, Group B: 65.2) (Figure 1). However, the difference in scores at 3 months was statistically significant (Group A: 73.8 points, Group B: 64.7 points, p-value: 0.017). Furthermore, even at 6 months, the difference in scores was statistically significant (Group A: 75.7 points, Group B: 64.6 points, p-value: 0.027).Conclusions: The cancer patient post-discharge management program based on Smart Cancer Care 2.0 was estimated to be effective in improving the health-related quality of life of breast cancer patients.Figure 1. Evaluation of the effectiveness of a cancer patient post-discharge management program through QLQ-C30 summary score Keywords: Patient Reported Outcome Measures; Mobile Applications; Breast Neoplasms; Patient Discharge

I. S. Marchal¹, E. P. Kuhn², J. M. Mikecz³, P. A. Pioli⁴, L. T. Vahdat²; ¹Medicine, Geisel School of Medicine, Hanover, NH, ²Medical Oncology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, ³Research Data Services, Dartmouth College, Hanover, NH, ⁴Microbiology and Immunology, Geisel School of Medicine, Hanover, NH.

Background: Chemotherapy-induced peripheral neuropathy (CIPN) affects at least 50% of patients (pts) who undergo systemic therapy. CIPN not only impacts quality of life but also adversely affects survival by frequently causing dose reductions, delays, or premature cessation of therapy. While the best strategy for preventing CIPN symptoms is currently cryotherapy, the exact mechanism remains elusive. It is hypothesized that cryotherapy prevents toxicity by modulating the neuroinflammatory process. Therefore, we posited that by systematically profiling the neuroinflammatory microenvironment in sera of patients enrolled in a completed prospective CIPN trial, the mechanisms of CIPN and those patients who are at highest risk for its development could be identified. Methods: This cohort consists of 14 pts with metastatic breast cancer enrolled in a phase 2 study of ixabepilone in which the primary endpoint of the original trial was to define the effect of ixabepilone on the development of CIPN and on the ultrastructure of neurons evaluated by electron microscopy of serial skin biopsies. Pts enrolled in this trial underwent an extensive clinical neurologic evaluation every 3 weeks using the Total Neuropathy Score-clinical (TNSc), a validated tool that utilizes both physical exam and patient report, to assess CIPN. In this study, severe CIPN was defined as the presence of a TNSc score of 10 or greater, a score increase of 4 or more points from baseline, or peripheral neuropathy that led to dose reduction, delay, or cessation of therapy. Using these criteria, 5 patients with severe CIPN and 3 patients without severe CIPN had sufficient serum sample available for analysis from the completed trial. Serum samples were collected at baseline and over time throughout the study, 18 timepoints among the patients with severe CIPN and 10 timepoints among the patients without severe CIPN were evaluated. Next, neuroinflammatory biomarker concentrations of the banked patient serum samples were measured with the Luminex 48-plex assay and custom discovery panels, allowing for the levels of 80 cytokines, chemokines, and growth factors to be measured in duplicate. Diluent and serum were combined in a well, incubated with mixed micro-beads, and then re-incubated with detection antibody and later streptavidin-phycoerythrin. The labeled micro-beads were then re-suspended in sheath fluid and analyzed by the Luminex 100 system. The instrument readout of mean fluorescent intensity (MFI) was converted to pg/ml based on MFI values of standards run alongside the samples in the assay. Results: Seven cytokines were significantly differentially expressed between the two groups. The MFI of the chemokine CCL24 was decreased over 3.2-fold in the group with severe CIPN compared to the group without severe CIPN (p<0.0001). CXCL2 (p<0.01) and IL-12 (p<0.05) were also significantly decreased in the severe CIPN group. Four biomarkers were elevated in the group with severe CIPN compared to those without severe CIPN: CCL8 (p<0.05), CCL18 (p<0.05), CCL23 (p<0.05), and PDGF-AA (p<0.05). Conclusions: Together, these seven biomarkers reveal a novel neuroinflammatory signature of CIPN. Elevated serum levels of CCL18 and PDGF-AA in patients with severe CIPN are suggestive of chemotherapy-induced pro-fibrotic macrophage activation, which has been shown to exacerbate neuropathy. While CCL8 and CCL23 have been reported in the literature in relation to peripheral neuropathy, this study marks the first report identifying CCL24 in this context. Decreased expression of CCL24 may be associated with a negative feedback regulatory mechanism, in which increased occupancy of CCR3, the receptor for CCL24, by additional endogenous ligands leads to downregulation of CCL24 over time. These results will be validated in a forthcoming prospective trial.

A. Kostara, T. Schaper, O. Opra; Gynecologic Oncology, MVZ Medical Center Duesseldorf, Duesseldorf, GERMANY.

Introduction: Advancements in oncology have significantly improved overall survival rates for cancer patients, particularly those with breast cancer. Consequently, the long-term side effects of chemotherapy—still a cornerstone of cancer treatment—on patients’ quality of life (QoL) are gaining increasing attention.Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect of taxanes (paclitaxel, nab-paclitaxel, docetaxel). CIPN can significantly reduce QoL and may lead to dose delays, reductions, or even treatment discontinuation. Reported incidence rates of grade 2-3 CIPN reach up to 50% with three-weekly and up to 30% with weekly taxane-based regimens, which are frequently used in breast cancer treatment.Temperature-controlled hand-foot cooling (Hilotherapy®) has shown potential in preventing CIPN. At our oncology department, Hilotherapy® is an established component of supportive care. We present here the results of our real-world data collection on 500 breast cancer patients who received prophylactic Hilotherapy® during chemotherapy. Methods: Temperature-controlled hand-foot cooling (Hilotherapy®) was used as a standard supportive care measure during each neurotoxic chemotherapy session. Hilotherapy® is a processor-controlled cooling system (Hilotherm ChemoCare CIPN) equipped with hand and foot cuffs that deliver continuous and precise cooling. The device uses distilled water and electricity to maintain the temperature.The standard procedure involved cooling the hands and feet for 30 minutes before, during, and 30 minutes after chemotherapy infusion. The device temperature was set to 15-17°C, resulting in a consistent skin surface temperature of 18-20°C.CIPN symptoms were assessed at each treatment cycle according to CTCAE v5.0 criteria. Patients were stratified by taxane dosing schedule (weekly vs. three-weekly). Follow-up data are currently being collected to evaluate long-term outcomes. Results: To date, 489 of the planned 500 patients have completed chemotherapy. Among them, 90.4% (n = 442) experienced only mild or no symptoms (CIPN grade 0-1), 9.4% (n = 46) developed CIPN grade 2, and only one patient (0.2%) experienced grade 3 CIPN.Key endpoints under evaluation include: Effectiveness of Hilotherapy® in preventing ≥ grade 2 CIPN; Time of first onset of CIPN; Dose reductions and/or treatment discontinuations due to CIPN; One-year follow-up data. Conclusion: Temperature-controlled hand-foot cooling (Hilotherapy®) effectively prevented ≥ grade 2 CIPN in over 90% of breast cancer patients. This method is a simple, well-tolerated, and easily implementable supportive care strategy. Patient satisfaction data will be presented in future analyses. Follow-up is ongoing to assess the long-term sustainability of the preventive effect.

E. Kanaya, K. Matsui, A. Urasaki, M. Furukawa, S. Nagasawa, M. Araki, K. Sukegawa, S. Sekine, T. Fujii; Surgery and Science, Faculty of Medicine, Academic Assembly, University of Toyama, Toyama city, JAPAN.

Chemotherapy-induced alopecia (CIA) is one of the most distressing side effects experienced by breast cancer patients undergoing adjuvant chemotherapy. In some cases, hair loss is incomplete or permanent (permanent CIA), significantly impairing quality of life, psychological well-being, and social reintegration. Although scalp cooling systems such as PAXMAN have shown effectiveness in reducing CIA, complete hair preservation is not achieved in all patients, and cases of permanent CIA still occur.HairRepro MEDI α is a novel scalp lotion containing a newly developed α-lipoic acid derivative, DHLH (histidine dithioloctamide with Na/Zn), which has been shown in preclinical studies to reduce inflammatory infiltration in the scalp induced by cytotoxic agents. A prior multi-institutional trial in Japan suggested its potential benefit in promoting hair regrowth among CIA-affected patients.This study is the first exploratory clinical trial in Japan to evaluate the combined use of the PAXMAN cooling system and HairRepro MEDI α, with the aim of improving not only CIA prevention but also post-chemotherapy hair regrowth and overall patient satisfaction. This retrospective exploratory study enrolled 22 breast cancer patients receiving adjuvant chemotherapy at our institution between 2022 and 2024. Chemotherapy regimens included HP+DTX→ddAC (n=8), HP+DTX (n=4), TC (n=2), ddAC→ddPTX (n=6), and others (n=2). HairRepro MEDI α was applied topically to the scalp and eyebrows at a dose of 4 mL twice daily, starting 6 days prior to the initiation of chemotherapy and continuing until day 90 post-final chemotherapy. PAXMAN scalp cooling was performed during each chemotherapy cycle. Photographs were taken at baseline (day −6), prior to each chemotherapy course, and on days 30, 60, and 90 after the final chemotherapy to assess hair loss percentage. Adverse events were recorded throughout. Among the 22 patients, the median hair loss at the final chemotherapy session was 45%, with 11 patients (50%) exhibiting Grade 1 or lower alopecia, indicating successful prevention. No adverse events related to the use of HairRepro MEDI α were observed.Hair loss typically began 4 to 6 weeks after the first chemotherapy dose. Compared to historical data from PAXMAN-only users, the onset of alopecia appeared delayed. Notably, all patients showed full scalp hair regrowth by 3 months post-chemotherapy, with hair loss scores returning to 0%, suggesting effective recovery.These findings indicate a potentially additive benefit of HairRepro MEDI α in both prevention and recovery from CIA when used alongside scalp cooling. The combination of PAXMAN and HairRepro MEDI α achieved favorable outcomes in the prevention and recovery of CIA among Japanese breast cancer patients receiving adjuvant chemotherapy. A 50% success rate for Grade ≤1 alopecia, along with complete hair regrowth by 3 months, suggests enhanced efficacy compared to previous studies involving scalp cooling alone. Notably, this is the first clinical report from Japan to evaluate this combination therapy, providing new insights into supportive care strategies tailored for Asian populations. Further randomized trials are warranted to confirm these preliminary findings and refine CIA management protocols.

S. Alkassis, L. Zhang, E. Yang, M. Lipsyc-Sharf, K. McCann, N. McAndrew, A. Master, J. LaBarbera, M. Sedrak, N. Palaskas, K. Greene, M. Kuiper, J. Glaspy, D. Elashoff, R. Callahan, A. Bardia; Hematology/ Oncology, UCLA Health Jonsson Comprehensive Cancer Center, Los Angeles, CA.

Background: Antibody-drug conjugates (ADCs) such as trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) have transformed the treatment of metastatic breast cancer (MBC). However, ADC-related alopecia remains poorly characterized. The effectiveness of scalp cooling in this setting is also unclear. Here, we evaluated the incidence and patterns of alopecia in patients (pts) with MBC treated with T-Dx and SG explored the potential protective effect of cold cap use. Methods: We identified pts with MBC treated with ADCs between June 2014 to June 2024 at UCLA using institutional databases. Pts were included based on ICD-9/10 codes for MBC, documentation of ADC use, and keywords related to scalp cooling discussion/ use in provider notes. Data were extracted on alopecia prior to ADC initiation (baseline alopecia), cold cap use during treatment, and alopecia development during ADC therapy based on clinical notes, patient self-report, and photographic documentation. Pts were stratified by pre-treatment alopecia status and ADC regimen (T-DXd, SG, or both sequentially). Those with alopecia attributed to neo/adjuvant chemotherapy administered at least one year prior to diagnosis of MBC were considered to have no baseline alopecia. Descriptive analyses were conducted to explore associations. Results: A total of 103 pts with MBC received ADC; T-DXd (n = 39), SG (n = 38), or both sequentially (n = 26). Disease subtypes included HR+/HER2− (36.8%), HR+/HER2+ (13.6%), HR−/HER2+ (12.6%), and TNBC (36.8%). Median age at MBC diagnosis was 54 years (range 26-80), and median duration of ADC treatment was 6.3 months (range 0-52.5). In the T-DXd group, 10/39 (25.6%) pts had baseline alopecia. Of the 29 pts without baseline hair loss, 10 (34.5%) developed alopecia while others did not have clear documentation of hair loss. Overall, 7 (of 29) pts without baseline alopecia used cold caps (4 [57.1%] developed alopecia) and 22 did not (6 [27.3%] had hair loss). In the SG cohort, 12/38 (31.6%) pts had baseline alopecia. Among the other 26 pts, 12 (46.2%) developed hair loss. Cold caps were used in 3 pts (2 [66.6%] had alopecia); of the 23 who did not use cooling, 10 (43.5%) experienced hair loss. Among the 26 pts who received both ADCs sequentially, 11 (42.3%) had baseline alopecia. Of the remaining 15 pts, 6 (40%) developed hair loss (5 during SG, 1 during T-DXd). One patient used a cold cap and did not have alopecia; among the 14 pts who did not use cooling, 6 (42.9%) developed alopecia. Conclusions: Alopecia is a common treatment-related toxicity among pts with MBC treated with T-DXd and/or SG. In this study, scalp cooling during ADC therapy was infrequent and appeared to offer limited protection against ADC-related alopecia. These findings underscore the need to develop innovative strategies to reduce hair loss risk with currently approved ADCs, as well as need to develop novel ADCs that do not confer alopecia risk for pts with breast cancer.

H. Koh, K. Yoon, H. Shin, E. Kim; Surgery, Seoul National University Bundang Hospital, Seongnam, KOREA, REPUBLIC OF.

Purpose: This study aimed to identify clinical, surgical, and treatment-related predictors of capsular contracture (CC) following immediate implant-based breast reconstruction after mastectomy, with particular emphasis on the influence of implant size relative to resected breast volume. Methods: We conducted a retrospective review of 465 patients who underwent nipple- or skin-sparing mastectomy and immediate reconstruction (direct-to-implant or two-stage) between 2004 and 2020. CC was defined as Baker grade II or higher. Capsular contracture-free interval (CCFI) was measured from final implant placement to first documented CC. Univariable and multivariable logistic regression identified CC risk factors. CCFI was assessed by Kaplan-Meier analysis and Cox proportional-hazards modeling. The optimal implant-to-breast weight ratio cut-point was determined using maximally selected rank statistics (surv_cutpoint). Results: Over a median follow-up of 63.7 months, 50 of 465 patients (10.8%) developed CC. In multivariable logistic regression, subpectoral placement (OR 3.28; 95% CI 1.05-10.21; P = 0.041) and postmastectomy radiotherapy (PMRT) (OR 4.94; 95% CI 2.27-10.74; P < 0.001) remained independent predictors of CC, whereas implant undersizing < 80% did not reach significance (OR 2.14; 95% CI 0.90-5.10; P = 0.085). In time-to-event analysis, PMRT alone independently shortened the capsular contracture-free interval (CCFI) (HR 4.04; 95% CI 2.11-7.74; P < 0.001). A maximally selected cut-point of 69.1% implant-to-breast ratio optimally stratified CC risk: patients with ratios ≤ 69.1% had significantly lower 1- and 5-year CCFI (84.2% and 75.8% vs. 96.5% and 90.3%; log-rank P < 0.001) and a threefold increased CC hazard in both unadjusted (HR 3.25; 95% CI 1.63-6.50; P < 0.001) and adjusted Cox models (HR 3.02; 95% CI 1.47-6.21; P = 0.003). Conclusion: Implant undersizing, particularly implant volumes ≤ 69.1% of resected breast volume, together with subpectoral placement and PMRT, are independent risk factors for capsular contracture. Careful matching of implant size to native breast volume may reduce CC risk in immediate reconstruction.

P. P. Advani, A. McPherson, J. Reddy, J. Schneider, S. Baheti, T. Nguyen, J. C. Ray, N. Norton; Hematology and Oncology, Mayo Clinic, Jacksonville, FL.

BACKGROUND: Anthracycline chemotherapy-related cardiomyopathy (CCM) is a serious adverse event that can occur several years after completion of breast cancer (BC) therapy. Demographic and clinical risk factors have failed to predict which patients will experience CCM. Genetic variants can account for a significant proportion of inter-individual variation. Knowledge of genetic risk variants prior to chemotherapy will be informative for risk stratification and early intervention. The goal of our study is to identify genetic variants that predispose patients to CCM.METHODS: We developed a cardiotoxicity registry at Mayo Clinic, Florida that enrolls patients who are to undergo standard of care chemotherapy in the early BC setting. Patients were (and continue to be) enrolled and consented for chart review and DNA sequencing. We sequenced whole exomes of the first 136 patients (anthracycline N=55, anti-HER2 (no anthracycline) N=71, other chemotherapy, N=10), primarily focusing on Titin (TTN) truncating variants, known to be present in ~25% of patients with primary dilated cardiomyopathy, and previously reported in 7.5% of patients with CCM, followed by exploration of increased burden of rare non-synonymous variants in 60 established genes for primary cardiomyopathy. Filtering of rare non-synonymous variants included minor allele frequency <0.5% (in GnomAD database European, African and Asian ancestries) and CADDv1.7 PHRED score ≥20.RESULTS: 18/55 (33%) patients treated with anthracycline experienced CCM. TTN truncating variants in were identified in 2/18 (11%) CCM patients and absent in 37 patients who did not experience CCM. Both patients with TTN variants had severe HF and required cardiac transplant. We identified a pathogenic variant in LMNA (p.Arg190Gln) in 1/18 (5.5%) patients and the same rare (p.Glu1127Gly) variant in RYR2 occurred in 2/18 (11%) of patients (Table 1). We noted enrichment of rare missense variants in anthracycline CCM patients compared to HER2 treated without anthracycline, CCM, p=0.0001.CONCLUSIONS: Pathogenic variants in TTN, LMNA, are enriched in BC patients (17%) who develop anthracycline-related cardiomyopathy. Early genetic screening may improve risk stratification and guide personalized cardiac monitoring to prevent CCM. Further research is needed to clarify the role of additional rare variants like RYR2 and to develop a CCM risk score based in idiopathic CM genes. Incorporating genetic risk assessments into treatment planning has the potential to enhance oncologic outcomes as well as long-term survivorship by preserving cardiac health.

R. Colombo Bonadio¹, L. Holland¹, C. A. Cavalcanti¹, J. Bessa¹, K. Cayres², P. do Amor Divino¹, R. Naves¹, J. Bines³, L. Testa¹; ¹Oncology, Instituto D’Or de Pesquisa e Ensino, São Paulo, BRAZIL, ²Oncology, Instituto D’Or de Pesquisa e Ensino, Recife, BRAZIL, ³Oncology, Instituto D’Or de Pesquisa e Ensino, Rio de Janeiro, BRAZIL.

Background: The use of abemaciclib in combination with endocrine therapy (ET) is an established adjuvant option for patients with hormone receptor-positive (HR+), HER2-negative early-stage breast cancer at high risk of recurrence. However, the prolonged treatment duration (up to two years) in the curative setting presents unique challenges related to tolerability and adherence, particularly given the known toxicity profile of CDK4/6 inhibitors. Diarrhea, fatigue, and hematologic adverse events are common and may lead to dose interruptions or permanent discontinuation. Real-world data are essential to better understand patient tolerance, frequency of dose adjustments, and their impact on treatment persistence and outcomes. We aimed to evaluate adjuvant abemaciclib use in a Brazilian real-world setting, focusing on adherence and the need for dose modifications. Methods: We retrospectively reviewed records of patients with high-risk, early-stage HR+ breast cancer who received adjuvant abemaciclib between 2019 and 2025. The endpoints evaluated included: initial dose, treatment interruptions, dose reductions, final maintenance dose, permanent drug discontinuation, and reasons for discontinuation. Results: A total of 189 patients were included, with a median age of 47 years (range 24-79); 58.7% were premenopausal and 37.0% postmenopausal. Most tumors were ductal (70.4%) or lobular (15.9%) in histology, stage II (45.0%) or III (38.1%), grade 2 (51.8%) or grade 3 (33.3%), and had a Ki-67 index ≥ 20% (77.2%). Nearly half of the patients (52.9%) had received neoadjuvant chemotherapy. For adjuvant ET, most patients (86.8%) initiated treatment with an aromatase inhibitor, and 53.9% received ovarian suppression.The majority (93.3%) initiated abemaciclib at the label dose of 300 mg daily (150 mg twice daily). At the time of analysis, 35 patients (18.5%) had completed the planned two years of treatment. In the overall cohort, dose interruptions occurred in 27.6% of cases and dose reductions in 43.1%. Maintenance dosing after adjustment was: 300 mg daily in 58.2%, 200-250 mg in 26.8%, 150 mg in 3.9%, and <150 mg in 11.1%. Permanent discontinuation due to adverse events was required in only 6.3% of patients, and all but one had undergone prior dose reductions. Grade 3 or higher diarrhea and neutropenia were registered in 6.3% and 7.4% of the cases, respectively. Among 152 patients with available adherence data, 91.5% reported good adherence (defined as taking ≥70% of prescribed doses). Conclusions: Our findings align with other real-world studies showing frequent need for dose adjustments during adjuvant abemaciclib therapy. Nevertheless, permanent discontinuation due to toxicity was infrequent, suggesting that proactive management through dose reductions can effectively support treatment persistence. Given that reduced doses do not appear to compromise efficacy, close monitoring of adverse events and timely dose adjustments are essential to maintain adherence and maximize benefit in the adjuvant setting.

X. Li¹, K. Lampson¹, K. Liou¹, Y. Li², Q. Li¹, T. Ahles³, J. Root³, J. Mao¹; ¹Integrative medicine service, Memorial Sloan Kettering Cancer Center, New York, NY, ²Department of Epidemiology and Biostatistics; Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY, ³Neurocognitive Research Lab, Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York, NY.

Background: Cancer-related cognitive difficulties (CRCD) is a multifaceted condition associated with various comorbid symptoms, making its management challenging. This study aims to evaluate cumulative symptom burden and its association with subjective and objective CRCD in breast cancer survivors. Method: We analyzed baseline data from a randomized clinical trial for addressing CRCD. The study included women with a history of stage 0-III breast cancer, currently free of oncologic disease, who reported moderate or greater CRCD and insomnia, as indicated by an Insomnia Severity Index score≥8. Subjective CRCD was assessed using the perceived cognitive impairment subscale from the Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog PCI). Objective CRCD was measured using the normed delayed T score from the Hopkins Verbal Learning Test—Revised (HVLT-R). Comorbid insomnia, fatigue, pain, anxiety, and depression were measured using Insomnia Severity Index, Brief Fatigue Inventory, PROMIS-Global pain item, and Hospital Anxiety and Depression Scale. We calculated a Cumulative Symptom Score based on co-morbid symptom severity to evaluate the cumulative symptom burden. Multivariable linear regression models were used to assess the associations between cumulative symptom burden and CRCD, adjusted for clinical and sociodemographic variables. Results: Among the 260 participants, the mean age was 56.6 years (SD 10.4), with 54 (21.0%) identifying as non-white and 26 (10.0%) as Hispanic survivors. The mean FACT-Cog PCI score and HVLT-R delayed T-score was 36.0 (SD 14.0) points and 46.0 (SD 12.7) points, respectively. A high prevalence of moderate to severe comorbid symptoms was observed in this population: fatigue (90%) being the most common, followed by insomnia (70.0%), pain (45.2%), anxiety (35.4%), and depression (11.5%). In multivariate analyses adjusted for age and chemotherapy, a higher Cumulative Symptoms Score was significantly associated with greater subjective CRCD (Coef. = -3.0, 95% CI = -3.6 to -2.4, p<0.001). Each comorbid symptom was also correlated with subjective CRCD (all p<0.001). However, the Cumulative Symptoms Score was not associated with objective CRCD (Coef. = -0.2, 95% CI = -0.9 to 0.5, p = 0.58); only insomnia had a significant correlation (r = -0.20, p<0.001). Conclusion: Higher cumulative symptom burden was associated with subjective perception of cognitive difficulties but not objective cognitive function among breast cancer survivors; however, insomnia was associated with worsened objective functions. Comprehensive symptom management has the potential to improve subjective appraisal of cognitive difficulties; targeted treatment of insomnia has the potential to improve objective cognitive functions in women with breast cancer.

C. Chiodi¹, F. Santos Dumont Sorice², T. Santana³, F. Oliveira⁴, M. Mathias Machado⁵, R. Brant Costa², M. de Azevedo Kalile¹, C. Pavei⁶, M. Borges Bittencourt⁶, D. Strassburger Nunes², H. Pantoja⁷, T. de Melo Passarini², M. Couto⁸, M. Behrends Pinto⁹, C. Perini¹⁰, C. Cerqueira Mathias¹, M. Laloni⁶, M. Cruz Rangel Silva², C. Alves Costa e Silva¹, L. Landeiro¹; ¹Oncoclínicas Bahia, Oncoclínicas&Co, Salvador, BRAZIL, ²Oncoclínicas Minas Gerais, Oncoclínicas&Co, Belo Horizonte, BRAZIL, ³Oncoclínicas Sergipe, Oncoclínicas&Co, Aracaju, BRAZIL, ⁴Oncoclínicas Espirito Santo, Oncoclínicas&Co, Vitória, BRAZIL, ⁵EBMSP, Escola Bahiana de Medicina e Saúde Pública, Salvador, BRAZIL, ⁶Oncoclínicas São Paulo, Oncoclínicas&Co, São Paulo, BRAZIL, ⁷Oncoclínicas Rio de Janeiro, Oncoclínicas&Co, Rio de Janeiro, BRAZIL, ⁸Oncoclínicas DF, Oncoclínicas&Co, Brasília, BRAZIL, ⁹Oncoclínicas Rio Grande do Sul, Oncoclínicas&Co, Porto Alegre, BRAZIL, ¹⁰Oncoclínicas Paraná, Oncoclínicas&Co, Curitiba, BRAZIL.

Background: Sexual dysfunction is a highly prevalent yet frequently underrecognized and undertreated issue among breast cancer survivors (BCS). Despite its impact on quality of life, discussions and management strategies are often lacking in routine care. This study examines post-treatment sexual symptoms, their association with emotional well-being, and partner relationships in BCS. Methods: We analyzed data from breast cancer survivors enrolled in “OC sobre VIVER”, a multicenter survivorship program coordinated by the Oncoclínicas Group (Brazil), representing one of the few structured survivorship care models in Latin America. Participants were 3-18 months post-active treatment. Structured interviews assessed sexual symptoms (vaginal dryness, dyspareunia, low libido), emotional status (self-esteem, depression, anxiety), and partner communication. Data was managed via REDCap. Descriptive and bivariate analyses were performed using GraphPad Prism, version 10. Results: From July 2023-March 2025, 391 women (median age 50 years [range: 30-86]) were enrolled. Of 376 women with staging data, 360 (95%) had invasive breast cancer (stage I: 55%, II: 33%, III: 12%). Notably, 92% (349/381) expressed a desire to address sexual health concerns during clinical encounters. Sexual dysfunction was prevalent: low libido in 67% (253/376), vaginal dryness in 65% (236/363), and dyspareunia in 31% (116/374). Psychosocial findings included low self-esteem in 31% (118/383) of participants, anxiety in 58% (225/387), and depression in 27% (104/387). Poor partner communication (among partnered) was reported in 10% (27/264). Dyspareunia was significantly associated with anxiety symptoms (p = 0.0003), but not with cancer stage, depression, or communication quality (p > 0.05). Low libido was more frequent with low self-esteem (75% vs. 64%, p = 0.043), higher stage (stage III: 15% vs. 4%, p = 0.008), hormonotherapy use (71% vs. 56%, p = 0.012) and showed a trend toward higher prevalence with poor partner communication (78% vs. 63%, p = 0.143). No associations with age, relationship status, or chemotherapy use (p > 0.05). Conclusions: Sexual symptoms were highly prevalent in this BCS cohort and encompassed both physical and psychosocial factors, including emotional distress and partner communication. These findings highlight critical opportunities for intervention. Routine assessment of sexual health and the integration of tailored, multidisciplinary strategies should be prioritized in survivorship care.

W. N. Riley¹, A. Ahn¹, J. Kroll², M. Chavez Mac Gregor³, M. R. Jones¹, G. Smith¹, K. Milbury¹; ¹Behavioral Science, MD Anderson, Houston, TX, ²Palliative Care medicine, MD Anderson, Houston, TX, ³Health Services Research, MD Anderson, Houston, TX.

Background: Patients with advanced-stage breast cancer and their spouse/romantic partners experience various challenges throughout their cancer journeys, including economic hardships sustained from treatment known as financial toxicity. Financial toxicity has been associated with poor physical and mental health, with some findings suggesting a bidirectional effect of financial toxicity on the dyad’s wellbeing. Previous literature indicates couples’ open and supportive communication behavior is associated with improved cancer-related adjustment. However, these associations have not yet been studied in the context of financial toxicity. This study aims to identify prevalent financial concerns, examine convergence and divergence in the reported financial concerns between patients and their spouse, and explore the associations between the couples’ communication behaviors and psychosocial wellbeing. Methods: The current cross-sectional data are part of a longitudinal study examining the psychological and behavioral impact of financial stress on patient-caregiver dyads. Eligible participants included women with stage III-IV breast cancer and their spouse. Upon enrollment, dyads completed separate baseline assessments for financial toxicity (COST), depressive (CES-D) and anxiety (GAD-7) symptoms, relational wellbeing (DAS-7), and positive and negative affect (PANAS). Afterwards, participants engaged in a standardized 30-minute spousal interaction task, where each dyad member identified and discussed a finance-related concern with a focus on problem solving for the selected issues. Results: 85 dyads (n=2 same-sex dyads; > $100,000 income: 64%; DAS-7 < 21: P=15%, S=12%; ≥Grade 1 COST: P=52%, S=47%) completed the spousal interaction task. Concerns regarding treatment side effects (P. = 19%, S. = 28%), future financial stability (P = 13%, S=20%) and discussing financial stressors with each other (P = 12%, S = 19%) were rated as most frequent concerns for both members of the dyad. Yet participants tended to avoid selecting some of the most pressing financial concerns as a discussion topic for the spousal interaction task. For instance, although spouses reported maintaining a steady income as a frequent concern (20%) but rarely (5%) discussed this topic during the interaction task. Changes in both positive and negative affect after participating in discussion were compared using paired t-tests. A significant reduction in negative affect (P < 0.001) was found for spouses, but not for patients. Significant correlations were found between COST to DAS-7, GAD-7 and CES-D for patients and spouses. For patients only, significant correlations were found between COST to Cancer Communication Assessment Tool (CCAT) and discrepancy and Social Provisions Scale (SPS) total score. Discussion: The results of this study support the notion that even well-adjusted, affluent couples may benefit from professional assistance in discussing and solving financial concerns. For the issues listed as most frequently concerning that remained unaddressed, there may be several underlying explanations (e.g. a perceived lack of control, a desire to avoid confrontation, etc.) for why dyad avoid discussion for certain topics. However, our results demonstrated that couples’ problem-solving discussions regarding financial toxicity decreased – rather than increased – negative affect in caregivers, indicating that dyads should embrace discussion of financial topics they may find distressing. We recommend that healthcare providers consider encouraging this behavior in breast cancer dyads to reduce stress and negative affect overall.

B. Worster¹, K. Parton²; ¹Supportive Oncology, Jefferson Health, Philadelphia, PA, ²Senior Data Modeler, EO Care, Boston, MA.

Guided cannabis care and improvements in PROMIS metrics among cancer patients: a prospective assessmentBackground:Cancer-related symptoms such as pain, sleep disturbances, anxiety, and gastrointestinal (GI) complaints often negatively impact patients’ quality of life. Patient-Reported Outcomes Measurement Information System (PROMIS) instruments were developed to quantify these domains and provide standardized, validated measures for clinical interventions. Given the growing interest in cannabis as an adjunctive therapy, we sought to determine whether guided cannabis care could enhance PROMIS-defined symptom outcomes among individuals with active cancer diagnoses.Methods:A total of 52 patients were enrolled from multiple oncology centers, dedicated marketing efforts, and various cancer advocacy organizations. At baseline, each patient completed PROMIS assessments for Pain Interference, Sleep Disturbance, Anxiety, and GI Nausea & Vomiting, as well as an intake survey covering health history and other personal information. Using a Bayesian model built from existing research and real-world data, a cannabis care plan was developed by integrating patient profiling inputs into individualized recommendations for products, dosages, and times of use. A clinician reviewed the plan before sending it to the patient. Patients then had scheduled follow-up surveys every 1–2 weeks to monitor efficacy, tolerability, and potential side effects. Regimens were adjusted as needed, based on patient feedback, to optimize therapeutic benefit and minimize side effects. Outcomes were evaluated at 4 weeks and again at 12 weeks. This approach allowed investigators to track changes in PROMIS metrics and assess any correlation between cannabis interventions and improved symptom management.Statistical Analysis:The primary endpoint looked at the proportion of patients achieving clinically meaningful improvement – defined as at least a 3-point reduction in T-score from baseline in PROMIS domains. At 4 and 12 weeks, the percentage of patients seeing meaningful improvement was calculated.Results:After 4 weeks of guided cannabis care (n=52), patients reported notable improvements across all measured PROMIS domains:Pain Interference: 69% of patients achieved clinically meaningful improvement.Sleep Disturbance: 75% saw improvements in sleep-related symptoms. Anxiety: 81% experienced reductions in anxiety.GI Nausea & Vomiting: 92% reported meaningful improvement.For those who continued treatment through 12 weeks (n=21), the proportion of patients demonstrating meaningful improvement increased further:Pain Interference: 88%Sleep Disturbance: 80%Anxiety: 100%GI Nausea & Vomiting: 100%Only 15% of patients experienced side effects, which included dizziness, anxiety, feeling overly intoxicated, or elevated heart rate. Qualitative feedback indicated that patients appreciated having structured guidance on which cannabis products to use, how to dose, and how to adapt their regimens to optimize their outcomes. This close monitoring and individualized adjustment appear to have supported sustained engagement and symptom relief.Conclusions:These findings suggest that guided cannabis care may significantly improve cancer-related symptoms as measured by PROMIS, a validated patient-centered metric. The high rates of clinically meaningful improvement in domains such as pain, sleep, anxiety, and GI symptoms underscore the potential role of guided cannabis use as an adjunct therapy.

M. Mathias Machado¹, T. Santana², F. Santos Dumont Sorice³, F. Oliveira⁴, C. Chiodi⁵, R. Brant Costa⁶, M. de Azevedo Kalile⁷, C. Pavei⁸, M. Borges Bittencourt⁸, D. Strassburger Nunes⁶, H. Pantoja⁹, T. de Melo Passarini⁶, M. Behrends Pinto¹⁰, M. Couto¹¹, C. Perini¹², C. Cerqueira Mathias⁵, M. Laloni⁸, M. Cruz Rangel Silva⁶, C. Alves Costa e Silva⁵, L. Landeiro⁵; ¹EBMSP, Escola Bahiana de Medicina e Saúde Pública, Salvador, BRAZIL, ²NOS, Oncoclínicas Sergipe, Aracaju, BRAZIL, ³Cancer Center Oncoclinicas, Oncoclínicas Minas Gerais, Belo Horizonte, BRAZIL, ⁴Cancer Center Oncoclinicas, Oncoclínicas Espirito Santo, Vitória, BRAZIL, ⁵NOB Ondina, Oncoclínicas Bahia, Salvador, BRAZIL, ⁶Oncoclínicas Minas Gerais, Oncoclínicas&Co, Belo Horizonte, BRAZIL, ⁷Oncoclínicas Bahia, Oncoclínicas&Co, Salvador, BRAZIL, ⁸Oncoclínicas São Paulo, Oncoclínicas&Co, São Paulo, BRAZIL, ⁹Oncoclínicas Rio de Janeiro, Oncoclínicas&Co, Rio de Janeiro, BRAZIL, ¹⁰Oncoclínicas Rio Grande do Sul, Oncoclínicas&Co, Porto Alegre, BRAZIL, ¹¹Oncoclínicas DF, Oncoclínicas&Co, Brasília, BRAZIL, ¹²Oncoclínicas Paraná, Oncoclínicas&Co, Curitiba, BRAZIL.

Introduction: With the growing number of cancer survivors, new challenges are emerging for this population. Among them, returning to work often represents a significant hurdle due to persistent physical and psychological toxicities resulting from both the disease and its treatment. Understanding the factors associated with work reintegration is key to promoting long-term quality of life and socioeconomic stability for breast cancer survivors (BCS). Methods: We analyzed data from breast cancer survivors enrolled in “OC sobre VIVER”, a multicenter survivorship program coordinated by the Oncoclínicas Group (Brazil), one of the few structured survivorship care initiatives in Latin America. Participants were 3-18 months post-active treatment. Structured interviews assessed employment status (work interruption during treatment, and return to work afterward), psychosocial aspects (supportive psychosocial network, self-esteem, emotional distress, anxiety, and depression), and treatment-related toxicities (cognitive deficits, arthralgia, pain, motor limitations, and neuropathy). Data was managed via REDCap. Descriptive and bivariate statistical analyses were performed using GraphPad Prism, version 10.Results: From July 2023-March 2025, 391 women were enrolled with a median age of 50 years (range: 30-86). Among 376 participants with available staging data, 360 (95%) had invasive breast cancer, distributed as follows: stage I (55%), stage II (33%), and stage III (12%). Employment status analysis revealed that 40.9% (158/386) of participants discontinued work during treatment. Among these, 56% (n=88) successfully returned to work, and 28% (n=43) required workplace accommodations to resume employment. Overall, 55% (197/356) were working at the time of data collection. BCS who received chemotherapy (CT) tended to have lower return-to-work rates compared to those who did not (48% vs. 62%, p = 0.093). In contrast, patients treated exclusively with hormonotherapy (HT) had a trend toward higher return-to-work rates compared to those who received both CT and HT (66% vs. 52%, p = 0.144). Similarly, BCS reporting symptoms of depression showed lower return-to-work rates than those without depression (44% vs. 56%, p = 0.117). Significantly lower return-to-work rates were also observed among participants who experienced treatment-related toxicities, including motor limitation (39% vs. 57%, p = 0.016), neuropathy (41% vs. 59%, p = 0.015), arthralgia (43% vs. 66%, p = 0.0004), and cognitive impairment (42% vs. 58%, p = 0.049). No statistically significant associations were found with tumor stage (p = 0.572), type of breast surgery (quadrantectomy vs. unilateral or bilateral mastectomy; p = 0.702), HER2-targeted therapy (p = 0.454), immunotherapy (p = 0.710), pain (p = 0.112), supportive psychosocial network (p = 0.844), emotional distress (p = 0.887), anxiety symptoms (p = 0.507), or low self-esteem (p = 0.202). Conclusion: The return to work after breast cancer treatment remains a significant challenge for many survivors, often contributing to psychosocial distress and financial toxicity. The development of structured survivorship care programs that proactively address physical, cognitive, and psychosocial sequelae is essential to support and facilitate a successful and sustainable return to the workforce.

G. Gorecki¹, O. Abioye¹, K. Babu¹, R. Srinishant¹, N. Gupta¹, C. Hilton²; ¹Internal Medicine, Allegheny Health Network, Pittsburgh, PA, ²AHN Cancer Institute, Allegheny Health Network, Pittsburgh, PA.

In triple-negative breast cancer (TNBC), pembrolizumab combined with chemotherapy has become a standard of care in both neoadjuvant and adjuvant settings, as established by the KEYNOTE-522 trial. Despite these clinical advances, immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs) that can affect multiple organ systems and result in substantial morbidity. In other cancer types, older patients have been shown to experience higher rates of irAEs, potentially due to age-related immune dysregulation and a higher burden of comorbidities, while younger patients often face distinct survivorship challenges. However, real-world data on age-specific irAE patterns and outcomes in TNBC patients receiving pembrolizumab are lacking. To date, no studies have specifically evaluated the differential impact of pembrolizumab-based therapy on irAE incidence, severity, and outcomes across age groups in TNBC populations.Methods This is a retrospective cohort study using TriNetX, TNBC patients treated with pembrolizumab between 2016 and 2024. Two age-stratified cohorts were created: younger (≤54 years) and older (≥55 years) of 1,661 patients per group after propensity score match. irAEs covering endocrine, hepatic, pulmonary, hematologic, and gastrointestinal toxicities were identified. Corticosteroid therapy and hospitalization were assessed as markers of toxicity severity. Kaplan-Meier survival curves were used.Results Older patients had a higher incidence of irAEs at 1 month (OR 1.43, 95% CI 1.01-2.04, p=0.048) and 3 months (OR1.43, 95% CI 1.11-1.79, p=0.0049), mainly due to thyroiditis (OR 1.67, 95% CI 1.08-2.13 p=0.017). Differences in irAE rates were no longer significant at 6 or 12 months. Despite lower irAE rates, younger patients had higher dexamethasone use at 3 months (OR 1.64, 95% CI 1.1-2.3, p=0.0047) and significantly worse survival (log-rank p=0.0071; HR 1.4, 95% CI 1.1-1.9). A composite marker of corticosteroid use and hospitalization showed younger patients consistently experienced more severe toxicities and poorer survival at all timepoints. At 1 month: OR 1.45, 95% CI 1.03-2.17, p=0.03; HR 1.3, 95% CI 1.01-1.9, log-rank p=0.04. At 3 months: OR 1.57, 95% CI 1.13-2.1, p=0.0087; HR 1.4, 95% CI 1.08-1.88, log-rank p=0.0105. At 6 months: OR 1.38, 95% CI 1.0-1.9, p=0.048; HR 1.3, 95% CI 1.03-1.69, log-rank p=0.027. At 12 months: OR 1.57, 95% CI 1.13-2.1, p=0.0063; median survival 171 days for younger vs. not reached in older group (log-rank p=0.0023; HR 1.49, 95% CI 1.1-1.8). At 3 months, total corticosteroid use and hospitalization remained higher in younger patients (OR 1.4, 95% CI 1.02-2.1, p=0.0359; HR 1.36, 95% CI 1.01-1.83; log-rank p=0.046). At 12 months, younger patients still had lower median survival (212 days vs. not reached; log-rank p=0.11; HR 1.2, 95% CI 0.95-1.59). While all-cause mortality was higher in older patients (p<0.0001), hospice referrals were similar between groups.ConclusionsIn this real-world cohort of TNBC patients treated with pembrolizumab, older patients experienced a higher incidence of early irAEs—particularly thyroiditis—but demonstrated superior survival. In contrast, younger patients had fewer documented irAEs but showed greater corticosteroid use, more frequent hospitalizations, and significantly worse survival across all timepoints when toxicity severity was considered. These findings suggest that irAE incidence alone may not fully capture clinical burden or risk and that age-related differences in immune response, toxicity manifestation, and management practices may contribute to divergent outcomes. Further investigation is warranted to elucidate the immunologic mechanisms of aging in the context of ICI use and safety to guide toxicity monitoring and supportive care strategies.

I. V. Critchfield-Jain¹, M. A. Fiala², Y. Park², E. Salerno³, L. Peterson²; ¹School of Medicine, Saint Louis University, St Louis, MO, ²Division of Oncology, Washington University School of Medicine, St. Louis, MO, ³Institute of Public Health, Washington University School of Medicine, St Louis, MO.

Background: For individuals with breast cancer undergoing chemotherapy, a nutritious, protein-rich diet may reduce side effects and improve outcomes. While emerging evidence supports the role of protein in managing cancer-related fatigue, few studies have focused on non-metastatic breast cancer or considered physical activity. This study examined the relationship between protein intake, physical activity, and fatigue in women with Stage I-III breast cancer receiving chemotherapy. Methods: This is a secondary analysis of the Genetics, Molecular Mechanisms, and Symptom Science (GEMMS) study, a longitudinal cohort of women undergoing curative-intent chemotherapy with follow up for 5 years. Protein and total caloric intake were assessed at baseline using the Automated Self-Administered Dietary Assessment (ASA24). Suboptimal protein intake was defined as 55 indicating clinically significant fatigue. Linear and logistic regression models evaluated associations between protein intake, exercise, and fatigue post-chemotherapy completion while adjusting for age, stage of cancer, chemotherapy intensity, and baseline fatigue. Results: A total of 95 women, median age 53 years [IQR 42-63] were included. Of these, 39% (n = 37) had suboptimal protein intake, with median protein intake of 0.88g/kg [IQR 0.60-1.12]. The characteristics of women with optimal and suboptimal protein intake are compared in Table 1. At chemotherapy competition, 41% (n = 39) reported clinically significant fatigue. This was numerically higher among women with suboptimal protein intake (43.2% compared to 39.7%) but did not reach statistical significance. In multivariable models, neither protein intake nor exercise were associated with fatigue. Baseline fatigue was the only consistent predictor: for each 1-unit increase in baseline fatigue T-score, the odds of post-treatment fatigue increased by 10% (aOR 1.10; 95% CI 1.03-1.17; p = 0.003). Conclusion: Protein intake and exercise were not significantly associated with fatigue during chemotherapy; however, baseline fatigue was a strong predictor of post-treatment fatigue. Future studies may benefit from exploring the micronutrient composition of dietary intake to discover other contributing factors to chemotherapy fatigue.

H. Sun¹, H. Lv¹, W. Chen², Y. Zhao³, M. Zhang¹, L. Niu¹, Z. Liu¹, X. Guo¹, X. Chen¹, Y. Feng¹, L. Wang¹, H. Zeng¹, J. Wang¹, Y. Cui¹, M. Yan¹; ¹Breast Cancer Centre, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, CHINA, ²Breast Cancer Centre, The Third Hospital of Nanchang, Nanchang, CHINA, ³Breast Oncology, Union Hospital, Tongji Medical College, Wuhan, CHINA.

Background: Cancer therapy-induced thrombocytopenia (CTIT) is a common complication of anti-tumor therapy and causes treatment delays or interruptions, increased bleeding risk and compromised outcomes. We aimed to evaluate hetrombopag, an oral thrombopoietin receptor agonist that prevented CTIT in breast cancer patients.Methods: In this multi-center, prospective exploratory trial (NCT05394285), breast cancer patients with platelet counts (PLT) 100×10⁹/L, which was defined as the thrombocytopenia treatment phase (TTP). Eligible patients were scheduled to continue the same anti-tumor regimen in their subsequent treatment cycle (Cycle 2). The secondary prevention phase (SPP) was initiated using a self-controlled design, with prophylactic hetrombopag (7.5 mg/day for 14 days) administration beginning one day after the start of Cycle 2. The primary endpoint was the response rate during the SPP, defined as the proportion of patients meeting all predefined criteria before the next treatment cycle (Cycle 3): 1. no platelet transfusion requirement; 2. no anti-tumor treatment modification (≥20% dose cut, ≥5 days delay, or discontinuation) ; 3. absence of severe thrombocytopenia (PLT <25×10⁹/L, or PLT <50×10⁹/L for ≥7 days).Results: Between Sep 2022 and May 2025, 67 breast cancer patients were enrolled in the study. After excluding 1 patient who withdrew informed consent, 66 patients comprised the full analysis set (FAS). During the trial, 6 patients discontinued participation in the SPP, the remaining 60 patients completed both TTP and SPP, forming the per-protocol (PP) population. In the FAS, 51 (77.3%) patients received antibody-drug conjugates (ADCs) monotherapy, 14 (21.2%) received regimens containing chemotherapy (RCC), and 1 (1.5%) with targeted therapy plus ADC. In the PP population, the response rate in the SPP was 85.0% (51/60). During the TTP, 86.7% (26/30) of patients in the hetrombopag group achieved response, compared to 80% (24/30) in the rhTPO group. No treatment-emergent severe adverse events occurred.Conclusions: As the first prospective trial to evaluate hetrombopag for preventing CTIT in breast cancer patients, this self-controlled exploratory study demonstrated hetrombopag may be a promising option for the secondary prevention of CTIT. The promising response rate observed during the TPP, coupled with a favorable safety profile, supports further large-scale investigation of hetrombopag for the prevention of CTIT in multi-cycle anticancer regimens.

S. Cocco¹, M. Cozzolino², M. Piezzo¹, R. Caputo¹, G. Celia³, D. Barberio⁴, V. Abate⁴, M. De Filippo⁵, V. Vaira⁶, A. Calabrese¹, C. Della Bella¹, A. Leone⁷, P. Mussnich De Freitas¹, E. Di Gennaro⁷, A. Budillon⁸, M. De Laurentiis¹; ¹Department of Breast and Thoracic Oncology, Division of Breast Medical Oncology, INT IRCSS Fondazione G. Pascale, naples, ITALY, ²Department of Human, Philosophical and Educational Sciences, University of Salerno, salerno, ITALY, ³Department of Psychology and Health Sciences, University of Pegaso, naples, ITALY, ⁴Departmental Structure of Clinical Psycho-oncology, INT IRCSS Fondazione G. Pascale, naples, ITALY, ⁵Division of Pathology, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milano, ITALY, ⁶Department of Pathophysiology and Transplantation, University of Milan, Milano, ITALY, ⁷Experimental Pharmacology Unit, INT IRCSS Fondazione G. Pascale, naples, ITALY, ⁸Scientific Directorate, INT IRCSS Fondazione G. Pascale, naples, ITALY.

Psychotherapeutic interventions, particularly those based on mind-body approaches, have demonstrated the ability to modulate inflammatory responses by downregulating the expression of inflammation-related genes and proteins. This has particular clinical relevance in breast cancer, where chronic inflammation is a well-established contributor to disease progression and resistance to therapy. Mind-Body Transformations Therapy (MBT-T) is an evidence-based therapeutic protocol designed to harness natural biological rhythms and biological plasticity in order to modulate gene expression. By reducing stress-induced dysfunctions, MBT-T facilitates the activation of endogenous healing mechanisms through the establishment of an optimal mind-body state. In our previous study (MBT-T Protocol 11/17) we demonstrated that MBT-T significantly reduced the serum levels of multiple cytokines and chemokines in breast cancer patients who had completed loco-regional treatment and adjuvant chemotherapy, compared to a matched control group not exposed to MBT-T. To further elucidate the molecular basis of these effects, we conducted a NanoString gene expression analysis on RNA extracted from blood samples collected from participants enrolled in the MBT-T study. The nCounter® Human Inflammation Panel, comprising 249 genes implicated in inflammatory and immune-related pathways, was used to evaluate gene expression changes at the end of the treatment (Tt) compared to baseline (T0). Matched timepoints were also analyzed in control patients. Consistent with our previous findings, MBT-T-treated patients exhibited a generalized downregulation of inflammatory gene expression at Tt compared to T0. Notably, we observed a significant reduction in the expression of genes associated with the interferon (IFN) signaling pathway, including OASL, OAS2, STAT2, IFIT1, IFIT3, and MX1. In contrast, the control group did not display significant modulation of inflammatory or IFN-related gene expression across timepoints. These findings are particularly meaningful given the complex role of the IFN pathway within the tumor microenvironment, where it influences immune cell dynamics, tumor cell behavior, and response to therapy. Elevated expression of IFN-related genes—such as OASL, OAS2, STAT2, and the IFIT family members—has been associated with immune evasion, angiogenesis, and tumor aggressiveness in several malignancies, including breast cancer. Collectively, our data suggest that MBT-T, through the reduction of psychophysiological stress, can downregulate key inflammatory signaling pathways, particularly those mediated by type I interferons. This modulation may influence tumor progression, reduce the risk of relapse, and enhance therapeutic responsiveness in breast cancer patients. These findings support the integration of mind-body interventions as adjunctive strategies in oncological care, with potential biological impact at the molecular level.

E. Fortune¹, A. Newell¹, R. Speck², A. Gilligan², M. Gonzalo¹, A. Searles Vitko³; ¹Research, Cancer Support Community, Washington DC, DC, ²HEOR Oncology, Global Medical Affairs, Eli Lilly and Co, Indianapolis, IN, ³Oncology, Medical Affairs, Eli Lilly and Co, Indianapolis, IN.

Background: Endocrine therapy (ET) is commonly used in the treatment of breast cancer, including both oral and intramuscular (IM) options. While ET is an effective treatment for breast cancer, the two administration modes may generate disparate burdens and benefits on patients’ everyday lives. This study aims to explore metastatic breast cancer (MBC) patients’ experiences with ET by describing the burdens (including challenges to administration and adherence), benefits, and preference of oral and IM ET. Method: Adults in the US with a history of taking both oral and IM ET consecutively for their MBC for at least 3 months completed an online survey. Participants were recruited via email and in-person at Cancer Support Community’s national network of 190 locations and 14 advocacy groups. Participants provided sociodemographic information and clinical history. Survey content included assessment of treatment-related considerations for oral and IM ET administration (i.e., convenience, pain, time, transportation, remembering, cost, access, distress, impact on eating) on a 5-point scale of burden vs. benefit (major or minor burden, neutral, major or minor benefit), and preference for oral vs IM ET. Participants also rated the importance, on a 5-point scale (not at all important to very important), of 11 factors when considering their MBC treatment options. Data collection is ongoing; results and conclusions are based upon interim data. Results: Interim data include responses from 100 women with MBC with a mean age of 54 years (range: 29-78), 69% non-Hispanic White, 24% urban. The average time since metastatic diagnosis was 6.6 years (median = 6). Approximately 58% of participants lived more than 30 minutes away from a treatment center. Duration on ET was longer for oral (median = 28 months) than for IM (median = 17 months); 76% indicated they started oral prior to IM ET. More than 80% of participants responded that oral ET was less painful to take, required less transportation and time, and was more convenient compared to IM ET. Most (65%) reported that oral ET interfered less with daily life compared to IM (17%). Top benefits of oral ET included ease of access (71% [major or minor benefit]), minimal time commitment (64%), and convenience (60%), while the stress or anxiety associated with having to take daily medication was the most common burden (37% [major or minor burden]). For IM ET, the main benefit reported was ease of remembering (60%), while the most frequently reported burden was pain or discomfort from the injection (84%). When comparing treatment modalities, 63% preferred oral, 18% preferred IM, 12% expressed no preference, and 7% were unsure. Self-reported adherence was better for IM vs oral ET, with 84% and 57% reporting they never missed a single dose, respectively. Among the 41% that missed at least one dose for oral ET, 88% missed ≤3 times a month. When asked about treatment priorities, nearly all participants (98%) found the ability to slow disease progression when considering treatment options an important priority (quite important or very important) followed by the ability to cure the disease (87%) and impact of treatment on daily life (85%). Conclusions: Findings suggest a clear preference for oral over IM ET, with most participants citing ease of access, convenience, and minimal disruption to daily life as benefits to oral ET. However, having to take oral medication daily was associated with stress and anxiety for some. Although self-reported adherence was better for IM ET, missing a single dose has different implications for the IM ET, which is given every 28 days, rather than daily like oral ET. While benefits and burdens are observed for both modes of administration, oral therapy is clearly preferred. These findings support the need for shared decision-making to help ensure treatment decisions are optimized with patient preferences.

Y. Li, Y. Cheng, L. Ji, Y. Wang, L. Yao, H. Zhang, H. Dong, M. Wang, X. Yingying; Department of Breast Surgery, First Hospital of China Medical University, Shenyang, CHINA.

Background:Thyroid dysfunction is among the most common immune-related events (irAEs) of immune checkpoint inhibitors (ICIs). This study aimed to investigate the prevalence, risk factors, and prognostic implications of thyroid irAEs in triple-negative breast cancer (TNBC) patients receiving neoadjuvant anti-PD-1 therapy combined with chemotherapy, based on data from the TREND phase II prospective clinical trial.Methods: The TREND study is a phase II prospective clinical trial involving TNBC patients treated with tislelizumab combined with nab-paclitaxel, followed by epirubicin-cyclophosphamide before surgery. Data on demographics, thyroid function, anti-thyroid autoantibodies were collected, and univariate and multivariate logistic regression models were used to identify risk factors. Peripheral immune analysis and whole-exome sequencing were conducted to explore underlying mechanisms associated with thyroid irAEs. Results: Among the 50 patients analyzed, 14 (28%) developed thyroid irAEs. Multivariate analyses revealed that baseline positivity of thyroglobulin antibody (OR 9.311, p=0.011) and lower levels of free triiodothyronine levels (OR 0.056, p=0.034) are independent predictors of thyroid irAEs. Peripheral immune analysis revealed that patients with thyroid irAEs exhibited elevated levels of CD4⁺ T cells, CD8⁺ T cells and CD16⁺CD56⁺ NK cells, along with higher levels of CD4⁺T cells before the onset of thyroid irAEs. Additionally, increased tumor mutational burden, and mutations in KLF17 and LRIG1 were observed in patients with thyroid irAEs.Conclusions: This study highlights the risk factors and underlying pathogenesis associated with thyroid irAEs in TNBC patients treated with neoadjuvant anti-PD-1 therapy combined with chemotherapy. These findings may assist clinicians in identifying patients at elevated risk for irAEs during ICI therapy, thereby improving patient management in clinical practice.Keywords:Thyroid immune-related adverse events; neoadjuvant immunotherapy; triple-negative breast cancer; predictive biomarkers

A. A. Shrebati¹, P. Loap¹, E. Mouret-Fourme², K. Cao¹, M. Belotti², D. Stoppa-Lyonnet², Y. Kirova¹; ¹Department of Radiation Oncology, Institut Curie, Paris, FRANCE, ²Department of Genetics, Institut Curie, Paris, FRANCE.

Background: Li-Fraumeni syndrome (LFS), caused by monoallelic germline pathogenic variant (PV) in TP53 gene, causes an elevated risk of developing certain cancers, mainly early onset breast cancer, sarcoma and brain tumors. While LFS patients are believed to be at an increased risk for radiation-induced sarcomas, only a few retrospective studies have been published studying the impact of radiationtherapy in the treatment of breast cancer among these patients. This study reviews the data concerning LFS patients treated at the Institut Curie with adjuvant radiation therapy for localized breast cancer. Methods: A retrospective study was conducted on female breast cancer patients with confirmed TP53 PV treated at the Institut Curie. Data concerning patients’ characteristics, treatments received, radiotherapy if received, rates of recurrences, rates of radiation induced sarcomas (RIS) and patient outcomes were collected. Results: From 1989 to 2024, we identified 47 female LFS breast cancer patients who met our inclusion criteria. Median age at diagnosis was 31 years (range 18-72). Of them, 76.6% had a family history of cancer suggestive of LFS. 31.9% had tumoral HER2 amplification. 51.1% received a mastectomy and 31.9% received a lumpectomy. 23 patients (48.9%) received radiotherapy as a part of their treatment strategy. The median follow up was 111 months (range 7-413). Among patients who received radiotherapy, 3 (13%) had a known diagnosis of LFS prior to treatment. No case of radiation-induced sarcomas was observed during the follow-up period. In the radiotherapy group, 5 patients (21.7%) later developed a malignancy within the irradiated field. At 10 years post-diagnosis, overall survival did not differ significantly between patients who received radiotherapy and those who did not (58.2% [95%CI: 36.8-91.9] vs. 80.1% [95%CI: 64.2-100]). Similarly, there was no significant difference in loco regional recurrence-free survival (95.2% [95%CI: 86.6-100] vs. 74.0% [95%CI: 54.8-99.9]) or in survival free from subsequent non-breast cancers (59.6% [95%CI: 36.5-97.2] vs. 67.2% [95%CI: 49.8-90.7]). Univariate analysis did not find any correlation between hormonal status, grade, surgical technique, stage, use or non-use of radiotherapy and overall survival, cancer-specific survival, loco regional recurrence-free survival, metastasis-free survival. Conclusion: The incidence of radiation-induced sarcomas and local recurrences in LFS breast cancer patients was lower than anticipated. Further studies with larger cohorts and extended follow-up are required to validate these findings.

A. Alpert¹, E. Sher-Cenzor², M. Makarov¹, A. Shai¹; ¹Oncology, RAMBAM Health care Campus, Haifa, ISRAEL, ²School of Psychology, University of Haifa, Haifa, ISRAEL.

Background: Chronic pain, subjective cognitive decline (SCD) and psychosocial distress (PD) are reported by > 40-60 % of patients recovering from breast cancer (BC). We previously reported that adverse childhood experiences (ACEs) are associated with increased pain and SCD before treatment. The effect of ACEs on pain and SCD during follow up has not been explored. Methods: We are conducting a prospective study to assess if ACEs increase chronic adverse effects in patients with localized BC and identify mediating mechanisms. Patients with stage I-III BC, age 18-75 without a history of prior cancer are recruited before starting (neo)adjuvant oncological treatment and assessed every 6 months by validated questionnaires, including ACEs, the brief pain inventory, FACT-COG and FACT-ES (measuring PD). Blood samples for inflammatory biomarkers are stored. This sub-study tested if ACEs are associated with pain, measured as a composite of pain intensity and interference, SCD and PD 6 months after treatment initiation, and with changes in these symptoms over time. Results: This sub-study included 116 patients with data collected 6 months from treatment initiation. Missing data ranged from 0.9% (n = 1) in ACEs to 9.5% (n = 11) in PD at 6 months and were imputed using the expectation maximization algorithm, as data were missing completely at random, Little’s MCAR test (229) = 242.51, p = .258. Of study participants, 68.1% were treated with chemotherapy, 62.9% had an academic degree, and 97.4% were employed prior to diagnosis. Univariate analysis did not detect an association between demographic or treatment factors and outcomes at 6 months (p’s > .14). Correlation analyses indicated that a higher number of ACEs was associated with more pain, SCD, and PD across time points (r range = .19 – .31, ps = < .048). A repeated-measures MANCOVA followed by Univariate analyses was conducted to examine changes over time in pain, SCD, and PD. Analyses included the number of ACEs (as a covariate), chemotherapy status (between-subjects variable), and time (within-subjects variable). The multivariate effect of time was significant, indicating that patients’ functioning declined over the 6 months, [Wilk’s lambda = .95, F (3,111) = 6.80, p < .001, partial η² = .16]. Specifically, pain [F (1,113) = 4.59, p = .034, partial η² = .04] and SCD [F (1,113) = 16.14, p < .001, partial η² = .13], but not PD [F (1,113) = 3.24, p = .074, partial η² = .03], increased between baseline and 6 months. ACEs had a significant main effect, F (3,111) = 4.81, p = .003, partial η² = .12. , and a higher number of ACEs was associated with worse pain, higher SCD, and higher PD on both timepoints [F_pain (1,113) = 13.43, p = .009, partial η² = .11; F_SCD (1,113) = 6.97, p = .009, partial η² = .06; and F_PD (1,113) = 7.96, p = .006, partial η² = .07]. The interaction between time and ACEs was not significant (p = .210) As expected, the interaction between time and chemotherapy was significant [F (3,111) = 3.50, p = .018, partial η² = .09; Univarite F’s (1, 113) > 4.14, p’s .03].Conclusion: Increasing numbers of ACEs predicts poor functioning of BC patients in terms of pain, SCD, and PD across the first 6 months post-diagnosis.

J. El-Taraboulsi¹, C. Rossou², M. Boland³, D. Leff¹, S. Cleator⁴, V. Harding⁴, P. Thiruchelvam¹; ¹Department of Surgery and Cancer, Imperial College Healthcare NHS Trust, London, UNITED KINGDOM, ²Department of Surgery and Cancer, United Lincolnshire Hospitals NHS Trust, Boston, UNITED KINGDOM, ³Department of Surgery and Cancer, St Vincent’s University Hospital, Dublin, IRELAND, ⁴Department of Oncology, Imperial College Healthcare NHS Trust, London, UNITED KINGDOM.

Introduction: Breast edema is a frequently under-reported and increasingly prevalent complication of breast cancer surgery. Currently, no unified definition or standardised diagnostic criteria exists, and there is limited evidence regarding its effective management and preventative strategies. The current literature suggests that breast edema is a long-term sequela of treatment, with a significant negative impact on patients’ quality of life. Methods: A systematic review of the literature was conducted according to PRISMA guidelines, examining the risk factors, diagnostic criteria, and management of breast edema following breast cancer surgery. Two independent reviewers conducted a comprehensive search of the Cochrane Library, PubMed, EMBASE, and additional sources from January 2000 to June 2025. Results: An initial keyword search identified 269 studies; following the application of eligibility criteria, 23 studies were included, encompassing 3,806 female patients with a mean age of 58.5 years-old, and an average BMI of 27.9. Of the included patients, 93.4% (n = 3,555) had undergone breast-conserving surgery, 4.4% (n = 168) have had mastectomies with free-flap or expander prosthesis reconstructions, and 2.2% (n = 83) have had therapeutic or prophylactic mastectomies without reconstruction. One study investigated breast edema in oncoplastic surgery, reporting this as a risk factor. Of the studies included, 21 reported on breast edema following adjuvant radiotherapy, despite inconsistencies in reporting, the most commonly cited radiotherapy schedule was 50Gy/25#. 39.1% (n = 9) of the articles investigated risk factors of breast edema, patient-related factors such as increased BMI and breast cup size were consistently reported as positive predictors of breast edema. There were conflicting findings with regards to tumour size and location, nodal involvement, and the extent of axillary surgery in relation to breast edema. Adjuvant radiotherapy and tumour bed boosts were associated with increased breast-edema, peaking at three to six months post-radiotherapy. Further potentially modifiable risk factors such as wound infection, and segmental post-operative scar-tissue burden were also proposed across studies. The reported incidence of breast edema following adjuvant radiotherapy was extremely variable, ranging from 7.1% to 75.5%, with high discordance based on the variability of definition and diagnostic methods. 43.5% (n = 10) of included studies focussed on the diagnosis of breast edema, including patient-reported outcomes measured with breast-edema related questionnaires, clinical examination, and imaging. Emerging investigations include dermal thickness measurement using High Resolution Ultrasound (HRUS) and tissue dielectric constant (TDC) as an accurate, non-invasive, and efficient quantitative measures of breast edema. Various studies have reported an inter-breast TDC ratio >1.40 as diagnostic for breast edema, while consensus has yet to be reached for the dermal thickness diagnostic threshold. The management and prevention of breast edema remains largely under-reported, with 17.4% (n =4) of included studies reporting this. Management options investigated in this review include compression garments, structured exercise programs and manual lymphatic drainage, though evidence supporting their efficacy remains inconsistent. Conclusion: Breast edema is a commonly overlooked but profoundly debilitating complication of breast cancer surgery, its aetiology is multifactorial, complex and distinct to breast-cancer related lymphedema of the arms. Improved prevention strategies, more timely and accurate diagnosis, and further assessment of more treatments is essential to optimise patient outcomes and quality of life.

J. Stal¹, K. E. Dibble¹, S. M. Rosenberg², C. Snow¹, A. H. Partridge¹; ¹Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, ²Department of Population Health Sciences, Weill Cornell Medicine, New York, NY.

Background: Many adolescents and young adults (AYAs) with early-stage breast cancer experience acute and chronic symptoms and survivorship concerns. Approaches used by AYAs to alleviate unmanaged symptoms and concerns and their perceived effectiveness remain poorly understood. This study qualitatively explored patient-reported symptoms, survivorship concerns, and alleviation methods reported by female AYAs newly diagnosed with early-stage breast cancer enrolled in a supportive care intervention study. Methods: Women (aged 18-39) newly diagnosed (<3 months) with early-stage (0-III) breast cancer at Dana-Farber Cancer Institute who were enrolled in Young, Empowered, and Strong (NCT04379414), a study testing a web and app-based supportive care intervention, were invited to participate in a virtual semi-structured qualitative interview. The interview guide was developed to explore experiences with management of symptoms and survivorship concerns. Areas of inquiry included burdensome symptoms and concerns, and challenges managing them. Transcripts were thematically analyzed. Results: AYAs (N=20) were, on average, 35 years at diagnosis (range: 33-39) and 1 year from diagnosis at interview (range: 0.65-1.77); most were non-Hispanic white (75%), partnered (80%), had stage I (40%) or II (40%) disease. Symptoms: Physical symptoms were the most frequently reported symptoms (e.g., menopausal symptoms, fatigue, nausea, pain, concentration/memory) by AYAs. For example, regarding pain, one AYA stated, “The mastectomy, the dissection, combined with the radiation side effects. I still experience a lot of pain in that area.” Methods to alleviate symptoms: Various methods were effective at alleviating (e.g., oncologist support, time) or somewhat alleviating (e.g., cold/heat therapy, medical marijuana) symptoms. Several methods, including diet, exercise, medication, and physical therapy, were effective for some but ineffective for others. For example, regarding exercise, one AYA shared, “Walking helps with the fatigue, and it helps with your sleep during the night,” while another shared, “For the exhaustion and fatigue, I haven’t found anything. I try everything they recommend…I tried riding a bike to exercise and that made my cording worse.” Survivorship concerns: Concerns spanned psychosocial (e.g., stress, anxiety, depression, isolation, fear of long-term treatment or recurrence, financial toxicity, fertility, sexual health), and clinical (e.g., transition from treatment to survivorship) domains. Methods to alleviate survivorship concerns: Various methods were effective at alleviating (e.g., religion/spirituality, medical marijuana) or somewhat alleviating (e.g., journaling, online research) concerns. Other methods were identified as ineffective (e.g., staying busy). Several methods, including therapy, medication, positivity/advocacy, and social support, were effective for some but ineffective for others. For example, regarding attending support groups for social support, one AYA shared, “I’m going to a seminar…I don’t have anyone to talk about [sex and relationships with], so I don’t think anyone would understand except cancer patients,” while another shared, “I joined [a] program thinking it would help to talk to other people, and I haven’t gone because I feel like I would actually feel worse if I were to hear other stories right now.” Conclusion: Female AYAs newly diagnosed with early-stage breast cancer who are receiving a supportive care intervention continue to report symptoms and survivorship concerns. AYAs use multiple methods to manage symptoms and concerns that vary in effectiveness, highlighting the need for diverse methods tailored to evolving patient needs alongside personalized survivorship care delivery to improve patient quality of life.

L. S. Agrawal¹, T. Kluthe², C. Menn³, E. Teplinsky⁴; ¹Medical Oncology, Norton Cancer Institute, Louisville, KY, ²Department of Pediatrics, University of Louisville and Norton Children Medical Group, Louisville, KY, Louisville, KY, ³Women’s Health, Alloy Women’s Health, New York, NY, ⁴Medical Oncology, Valley-Mount Sinai Comprehensive Cancer Center, Paramus, NJ.

Background: Sexual health symptoms are common and distressing in breast cancer survivors. There is limited data regarding the experience with sexual health among patients with metastatic breast cancer (MBC). Given the chronic nature of MBC and ongoing treatments, sexual health concerns may be especially complex and underrecognized in this population. We previously reported data from the WISH-BREAST study evaluating sexual health in breast cancer survivors. Here, we present findings from the WISH-BREAST MBC cohort. Methods: An anonymous online survey on sexual health in breast cancer survivors was distributed through a social media platform (Instagram) and e-mail. Questions included demographics, breast cancer history and treatment, sexual health symptoms and experience with medical care for sexual health symptoms. Results: There were a total of 1775 responses to the survey. 42 reported having MBC and 1420 reported Stage 0-III; these respondents were included in this analysis. The median age of MBC respondents was 44 years (range 39-53 years). Median age at diagnosis was 39 years (range 33-45 years) – younger than the non-MBC respondents. MBC respondents were more likely to report early menopause (57.1% vs 28.2%). 100% of respondents with MBC reported changes to sexual health. 95.2% reported a moderate to great deal of distress related to sexual health changes. The sexual health concerns reported are summarized in Table 1. Respondents with MBC were more likely to report painful sex (78.6% vs 58.8%), no sexual pleasure (52.4% vs 33.4%), and that sexual health concerns impacted relationships (85.7% vs 71.4%) than non-MBC respondents. The majority of respondents with MBC obtained information about sexual health from social media, although a lower percentage compared to those with non-MBC (66.7% vs 80.5%). While 95.2% of respondents with MBC reported vaginal dryness, 64.3% reported that treatment with vaginal hormones was not discussed. A similar proportion of respondents with MBC reported being prescribed vaginal estrogen compared to respondents with non-MBC (23.8% vs 22.7%). Conclusions: In this online survey, respondents with MBC reported high rates of sexual health concerns and distress. Despite the prevalence of symptoms such as vaginal dryness, painful sex and loss of sexual pleasure, conversations around management options, including vaginal hormones, remain limited. These findings underscore critical gaps in clinical care and patient-provider communication regarding sexual health in the metastatic setting and highlight the potential role of social media an information source. Integrating sexual health discussions into routine MBC care, improving access to evidence-based treatments and sexual health programs, and including patients with MBC in clinical trials focused on sexual health are essential steps toward enhancing quality of life for this population.

A. Murakami¹, M. Manae¹, U. Kaho¹, T. Kana¹, N. Megumi¹, K. Erina¹, N. Haruna¹, T. Kana¹, K. Yoshiaki¹, U. Yuzo²; ¹Breast center, Ehime University Hospital, Toon,Ehime, JAPAN, ²Department of Hepato-Biliary-Pancreatic Surgery and Breast Surgery, Ehime University, Toon,Ehime, JAPAN.

Background:Bone-modifying agents (BMAs), such as zoledronic acid and denosumab, are standard treatments for reducing skeletal-related events in breast cancer patients with bone metastases. Medication-related osteonecrosis of the jaw (MRONJ) is a well-recognized adverse event, particularly after prolonged treatment. Despite this risk, little data exist on the long-term incidence and prognostic implications in real-world practice.Methods:We retrospectively reviewed breast cancer patients with bone metastases who received BMAs for ≥3 months between January 2015 and December 2024 at our institution. Patients who received radiotherapy to the oral cavity or jaw were excluded from the study. Data were collected from the electronic medical records. MRONJ was diagnosed according to established clinical criteria. Overall survival (OS) was compared between patients with and without MRONJ using the Kaplan-Meier method.Results:A total of 46 female patients (median age, 58 years; range, 35-90 years) were included. Thirty-six patients (78.2%) underwent dental assessment before BMA initiation, and 19 (41.3%) underwent tooth extraction. The median treatment duration was 33 months (range 6-85). MRONJ occurred in 16 patients (34.8%) with a median onset time of 23.5 months. Six cases were triggered by tooth extraction during the treatment. Fourteen patients were managed conservatively, and two required surgical debridement.The median OS was significantly longer in the MRONJ group (2048 vs. 1092 days; p=0.0332), with no difference in BMA duration between the groups.Discussion and Conclusion:Our cohort showed a high incidence of MRONJ, which is consistent with previous long-term data. Notably, MRONJ was associated with a longer OS. Although its causality remains unclear, MRONJ may reflect prolonged disease control or more intensive care. These findings support the continued use of BMAs with proper dental monitoring and aggressive management of MRONJ. Prospective studies are warranted to explore prognostic implications and optimize supportive care strategies.These findings highlight a rare but clinically significant adverse event associated with prolonged use of BMAs in patients with breast cancer. Although the sample size was limited, the long-term follow-up and detailed analysis of dental intervention strategies provided valuable insights for real-world clinical management.As this analysis was conducted exclusively in an Asian population, the findings may offer unique insights into MRONJ risk and outcomes in non-Western breast cancer cohorts, where data remain limited.

D. Amarillo, J. Manzanares, B. Insagaray, M. García, N. Camejo, C. Castillo, G. Krygier; Unidad Academica Oncología Clínica, Universidad de La Republica (UdeLaR), Facultad de Medicina, Hospital de Clínicas, Montevideo, URUGUAY.

Background:Chemotherapy-induced alopecia (CIA) is one of the most distressing side effects of systemic treatment in early-stage breast cancer (ESBC), negatively impacting quality of life (QoL) and sometimes leading patients to reject curative regimens. DigniCap® is an FDA-approved scalp cooling system recommended by NCCN and ESMO guidelines. However, regional evidence for Latin America is scarce, and differences in hair type, access, and health system structure may affect outcomes. This study examines the real-world efficacy and tolerability of DigniCap in Uruguayan patients, comparing results between the public university hospital (Hospital de Clínicas) and private clinics. Methods:A prospective single-arm cohort included Uruguayan women with ESBC receiving adjuvant or neoadjuvant anthracycline/taxane-based chemotherapy (March 2022-June 2025). Hair loss was evaluated using Dean’s scale (success: Dean 0-2). The primary analysis focused on CIA prevention rates and device discontinuation by care setting. Results:Among 122 patients, overall success was 83.6% (≤50% hair loss). Device discontinuation due to chemotherapy toxicity or DigniCap intolerance occurred in 17%. By care setting: Public (HC, n=49): Success 75%; discontinuation 24.5%. Private patients (n=73): Success 84.9%; discontinuation 4,1%. The highest success rates were seen with the TCHP (85,7%) and TC (85.4%) regimens. Reported adverse events included headaches, scalp discomfort, and cold intolerance, which were mostly mild. 83.1% of participants completed all planned cycles with DigniCap. Conclusions: This first Uruguayan cohort demonstrates that DigniCap is effective and well-tolerated for CIA prevention, achieving outcomes comparable to those of international trials. The success gap and higher discontinuation rate among public hospital patients underscore the need to address logistical barriers, provide hair care counseling, and offer supportive resources to ensure equitable benefits across all settings. Regional real-world data support the advocacy for broader insurance coverage and tailored protocols to enhance patient acceptance and treatment adherence. Local evidence on DigniCap® strengthens the case for implementing scalp cooling programs in Latin America, considering specific hair characteristics, health system inequities, and patient-centered QoL goals.

F. Khan¹, M. Zafar¹, B. Singeltary²; ¹Hospice and Palliative Medicine, University at Buffalo Roswell Park Comprehensive Cancer Center, Buffalo, NY, ²Hematology and Oncology, TriHealth Good Samaritan Hospital, Cincinnati, OH.

Background: Alpelisib, a PI3Kα-specific inhibitor, is approved for use in hormone receptor-positive (HR+), HER2-negative advanced breast cancer with PIK3CA mutations. However, its known metabolic side effects, particularly hyperglycemia, raise concerns for patients with pre-existing Type 2 Diabetes Mellitus (T2DM). This study aimed to evaluate real-world treatment patterns and clinical outcomes in breast cancer patients treated with Alpelisib, stratified by diabetes status. Methods: We conducted a retrospective analysis using the TriNetX US Collaborative Network. Two cohorts were identified: (1) patients with breast cancer and T2DM treated with Alpelisib (n=655), and (2) patients without diabetes treated with Alpelisib (n=1,102). Treatment pathways were analyzed separately for each cohort. A comparative outcomes analysis was performed using 1:1 propensity score matching (503 patients per cohort) to balance baseline characteristics. Kaplan-Meier survival analysis was used to evaluate time-to-event outcomes. Patients with prior outcomes were excluded from each respective analysis. Results: After matching, each cohort included 503 patients. Mean follow-up was 562.2 days (SD 484.1) for the T2DM group and 525.1 days (SD 459.7) for the non-diabetic group. Among those without prior death records, 268 of 502 (53.4%) T2DM patients and 274 of 502 (54.6%) non-diabetic patients died during follow-up (median survival: 651 vs. 575 days; HR 0.948, 95% CI: 0.801-1.122, p=0.747). For hospitalization, 67 of 201 (33.3%) T2DM patients and 83 of 233 (35.6%) non-diabetics were hospitalized (median time: 1,178 vs. 1,009 days; HR 0.808, 95% CI: 0.584-1.116, p=0.631). Cancer progression occurred in 24 of 79 (30.4%) T2DM patients and 27 of 75 (36.0%) non-diabetics (median time: 799 vs. 765 days; HR 0.769, 95% CI: 0.443-1.337, p=0.381). Regarding adverse events, T2DM patients had a higher risk of hyperglycemia (95 of 294 [32.3%] vs. 116 of 463 [25.1%]; HR 1.336, 95% CI: 1.018-1.752, p=0.036). For hypokalemia, rates were similar (88 of 360 [24.4%] T2DM vs. 93 of 406 [22.9%] non-diabetics; HR 0.985, 95% CI: 0.735-1.318, p=0.444). Dermatitis was seen in 35 of 453 (7.7%) T2DM patients vs. 42 of 455 (9.2%) non-diabetics (HR 0.791, 95% CI: 0.505-1.239, p=0.249). Heart failure occurred in 37 of 441 (8.4%) T2DM vs. 34 of 474 (7.2%) non-diabetics (HR 1.120, 95% CI: 0.703-1.785, p=0.282). Myocardial infarction rates were 19 of 494 (3.8%) T2DM and 17 of 484 (3.5%) non-diabetics (HR 1.055, 95% CI: 0.548-2.031, p=0.593). Diarrhea occurred in 62 of 324 (19.1%) T2DM and 87 of 386 (22.5%) non-diabetics (HR 0.831, 95% CI: 0.600-1.152, p=0.283). Pneumonitis developed in 20 of 468 (4.3%) T2DM vs. 15 of 467 (3.2%) non-diabetics (HR 1.284, 95% CI: 0.657-2.509, p=0.806). Treatment pathway analysis revealed that breast cancer patients with T2DM were seven times more likely to discontinue or not proceed to subsequent therapy after Alpelisib compared to non-diabetics, despite similar follow-up durations. Conclusions: In this large real-world cohort, breast cancer patients with T2DM treated with Alpelisib experienced comparable survival and cancer progression outcomes to those without diabetes. However, they were at significantly higher risk for hyperglycemia and had less complete treatment documentation, potentially reflecting clinical complexity or data capture limitations. These findings underscore the importance of proactive metabolic monitoring and individualized care strategies for patients with comorbid diabetes receiving Alpelisib. Further research is warranted to optimize treatment sequencing and mitigate toxicity in this high-risk population.

T. Yordanov, P. Spasov, M. Musin, I. Pandzharova, S. Tuncheva, T. Karanikolova, S. Velchova, A. Konsoulova; Medical oncology, University Specialized Hospital for Active Treatment in Oncology Prof. Ivan Chernozemski, Sofia, BULGARIA.

Background:Early supportive care integration improves quality of life and may enhance survival in patients with advanced breast cancer. However, identifying the right timing and patient subset for such interventions remains a challenge in routine clinical settings. SPIRE (Supportive care & Prognostic Insights in Risk Evaluation) is a pragmatic screening tool that incorporates clinician judgment and key clinical variables to stratify oncology patients into risk groups for targeted early supportive care intervention. Methods: We performed a subgroup analysis of breast cancer patients (ICD code 50) within a prospective departmental implementation of SPIRE from April to June 2025 at the Medical oncology clinic, University Hospital of Oncology Prof. Ivan Chernozemski, Sofia. The SPIRE score integrates the surprise question (12-month mortality), ECOG status, metastatic burden, brain metastases, and comorbidities. Patients were stratified into low (0-1), medium (2-3), or high (≥4) risk categories. Referral to supportive care and preliminary follow-up status were tracked. A prospective validation strategy was pre-planned with three time-based cutoffs (month 4, 8, and 12) to evaluate the prognostic value of SPIRE in predicting 12-month mortality. Due to the prospective, pragmatic design, data reflects visit-level documentation; patient-level analyses are planned as the dataset matures. Results:Across 1,711 recorded visits between April and June 2025 (representing 737 unique breast cancer patients), 1,279 visits (74.7%) were categorized as low risk, 342 (20.0%) as medium risk, and 85 (5.0%) as high risk. Metastatic disease was present in 946 visits (55.3%), brain metastases in 86 (5.0%), and clinically significant comorbidities in 313 (18.3%). ECOG ≥2 was recorded in 89 visits. Referral to supportive care was documented in 190 visits (11.1%). Follow-up SPIRE score transitions were analyzed in 969 instances. Preliminary trend analysis showed worsening in 131 cases (13.5%) and rapid deterioration (defined as ≥2-point score increase within ≤7 days) in 8 patients. The mean normalized score change was +0.03 (SD ±2.74). These findings support the tool’s dynamic tracking potential, pending formal prospective validation. Conclusions:SPIRE is feasible to implement in routine breast cancer care and effectively stratifies patients based on prognosis and complexity. Its prospective validation will assess real-world prognostic performance, with the goal of enhancing timely and personalized supportive care delivery. Early findings suggest that SPIRE may serve as a valuable clinical trigger for palliative care referrals in breast cancer patients.

X. Yan, Y. Liang, X. Huang, Y. Yin; Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, CHINA.

Objective: To evaluate the efficacy and safety of topical La Roche-Posay New B5 Multi-Effect Soothing and Repairing Cream in the treatment of skin adverse reactions related to EGFR inhibitors and capecitabine.Methods: A randomized, double-blind, controlled clinical study was conducted. From October 2024 to June 2025, 40 patients with skin adverse reactions (such as rash, hand-foot syndrome, pruritus, dryness, discoloration, and skin chapping) during anti-tumor therapy (EGFR inhibitors and capecitabine) were recruited from the First Affiliated Hospital of Nanjing Medical University. They were divided into two groups with 20 cases each. The experimental group was treated with topical La Roche-Posay New B5 Multi-Effect Soothing and Repairing Cream, while the control group was treated with topical silicone oil cream, twice daily for 8 weeks. Follow-ups were conducted before treatment and at 2, 4, 6, and 8 weeks after treatment. Efficacy was evaluated based on the improvement rate of rash grade, the improvement time of rash grade, the improvement rate of hand-foot syndrome grade, the improvement time of hand-foot syndrome grade, Visual Analogue Scale (VAS), and Dermatology Life Quality Index (DLQI). Adverse events were recorded. Repeated measures analysis of variance and chi-square test were mainly used to compare efficacy and safety.Results: A total of 40 patients participated in this clinical study, including 22 males and 18 females, with age of (54.21 ± 14.47) years. Before treatment, there were no statistically significant differences between the two groups in gender, age, rash grade, hand-foot syndrome grade, VAS score, or DLQI score (all p > 0.05). After 2 weeks of treatment, the improvement rates of rash grade and hand-foot syndrome grade in the experimental group were 20.00% (2/10) and 20.00% (2/10), respectively, while those in the control group were 10.00% (1/10) and 20.00% (2/10), respectively. There were no statistically significant differences between the two groups (p > 0.05). After 4 weeks of treatment, the effective rate (rash grade improvement rate + hand-foot syndrome grade improvement rate) in the experimental group was 65.00% (13/20), which was significantly higher than that in the control group (40.00%, 8/20, p < 0.05). After 8 weeks of treatment, the effective rate in the experimental group was 70.00% (14/20), which was significantly higher than that in the control group (45.00%, 9/20, p < 0.05). After 4, 6, and 8 weeks of treatment, the VAS and DLQI scores in the experimental group were significantly lower than those in the control group (all p < 0.05).Conclusion: La Roche-Posay New B5 Multi-Effect Soothing and Repairing Cream is safe and effective in the treatment of skin adverse reactions related to EGFR inhibitors and capecitabine. It can significantly improve rash and hand-foot syndrome after 4 weeks of use and can be applied clinically.

K. Lee¹, E. Kim¹, L. Youra¹, A. Ham¹, J. Jo¹, S. Lee¹, H. Kim², J. Lee², J. Woo², W. Lim², B. Moon², S. Ahn², H. Lee³; ¹Medical Oncology, Ewha Womans University Mokdong Hospital, SEOUL, KOREA, REPUBLIC OF, ²Surgery, Ewha Womans University Mokdong Hospital, SEOUL, KOREA, REPUBLIC OF, ³Statistics, Ewha Womans University Mokdong Hospital, SEOUL, KOREA, REPUBLIC OF.

Introduction: In the treatment of hormonal receptor positive (HR+), HER2 negative (HER2-) metastatic breast cancer (MBC), most guidelines recommend endocrine therapy including CDK4/6 inhibitors as the first-line drug for quality of life. Ribociclib is one of the CDK4/6 inhibitor and has been used with aromatase inhibitors or fulvestrant in HR+, HER2- metastatic breast cancer patient. Various drug reactions related with ribociclib has been reported including skin reaction, liver toxicity and hematologic toxicity. In this study, we aimed to evaluate clinical manifestations and risk factors of dermatologic toxicities in metastatic breast cancer patients who used ribociclib. Method: This study included the patients with metastatic/recurrent breast cancer who were prescribed ribociclib from April 2021 to December 2024 in our single institution. We retrospectively reviewed the medical records of the patients, identified the frequency of recorded skin lesions, the time of occurrence and clinical characteristics of skin reactions. Logistic regression analysis was performed with several clinical factors including BSA (body surface area) and concomitant medications to analyze risk factors related to the occurrence of skin lesions. Results: A total of 110 MBC patients were enrolled during the period. The median was 53 years-old (28-82), 110 patients (100.0%) were female, median BSA was 1.56 m2(range, 1.29~2.07) and 33 patients (30.0%) showed pre-menopausal status. There were 44 de novo metastatic patients (40.0%) and 66 recurrent patients (60.0%). Ribociclib+letrozole was used in 81 patients (73.6%) and ribociclib+fulvestrant was used in 29 patients (26.4%). Skin toxicity occurred in 29 patients (26.4%), and the median time to skin toxicity onset was 84 days (range, 3-498). Skin toxicity patterns included pruritus, erythematous patches, vitiligo, bullous patches, and desquamation. Grade 1 or 2 skin toxicity occurred in 93.1% of patients, grade 3 skin toxicity occurred in 1 patient and grade 4 toxicity, toxic epidermal necrolysis (TEN), was reported in 1 patient. Dose reduction was done in 7 patients (24.1%) and permanent discontinuation of ribociclib occurred in 1 patient (3.4%). Clinical improvement was achieved in 86.2% of patients with skin reactions following supportive care. Logistic regression analysis results for dermatologic toxicity risk showed that age, ECOG PS, BSA, treatment regimen, hyperlipidemia, and use of statins (HMG-CoA reductase inhibitors) were not risk factors for skin toxicity development. Conclusions: CDK4/6 inhibitors are one of the important treatments for HR+, HER2- MBC. Regardless of clinical efficacy, skin toxicity is a common cause of patient discomfort. Therefore, detailed clinical attention and supportive cares can improve the patient’s quality of life.

I. BLANCAS¹, M. MARTINEZ PEREZ², X. DIAZ VILLAMARIN², F. RODRIGUEZ SERRANO³, R. MORON⁴; ¹MEDICAL ONCOLOGY, HOSPITAL, GRANADA, SPAIN, ²PHARMACY, HOSPITAL, GRANADA, SPAIN, ³Associate Professor Department of Human Anatomy and Embryology, UNIVERSITY, GRANADA, SPAIN, ⁴MEDICAL ONCOLOGY, PHARMACY, GRANADA, SPAIN.

The UGT1A1*28/*28 genotype is linked to reduced UGT1A1 enzyme activity and increased toxicity risk. This study assesses the potential clinical and economic impact of preemptive UGT1A1*28 genotyping in SG-treated patients. Methods:We conducted a retrospective study (Aug 2024-Jul 2025) involving 15 metastatic breast cancer patients treated with SG. UGT1A1*28 genotyping (via KASP probes; €10.51/patient) was performed in those experiencing grade ≥3 toxicities (n=8). Clinical, hospitalization, and cost data were retrieved using official Andalusian Health Service pricing (May 2024), including DNA extraction and lab expenses.Results: Three patients required hospitalization:

One UGT1A1*28/*28 patient was admitted to the ICU (5 days) and internal medicine ward (6 days) due to septic shock with febrile neutropenia (grade 4) and other toxicities (total cost: €14,553.08)One UGT1A1*1/*28 patient was hospitalized for 11 days due to febrile neutropenia (grade 4) and gastrointestinal toxicity (€8,485.73)Another UGT1A1*28/*28 patient was admitted to the oncology ward for 3 days due to grade 4 neutropenia (€2,314.29)

The total cost of preemptively genotyping all 15 patients would have been only €157.65.

The median PFS among evaluable patients was 6.5 months. Two patients remained on treatment without progression at data cutoff. Although no formal comparison by genotype was performed due to sample size, patients with the UGT1A1*28/*28 genotype showed a trend toward shorter treatment duration due to early-onset toxicity and treatment discontinuation.According to RECIST 1.1 criteria, there were 2 partial responses (PR), 4 cases of stable disease (SD), 1 progressive disease (PD), and 1 unevaluable case due to early discontinuation caused by persistent toxicity (UGT1A1*28/*28 carrier).Regarding clinical management, all UGT1A1*28/*28 patients required dose reductions, treatment discontinuation, or G-CSF support. Two underwent progressive dose reductions (up to 70%), and one discontinued SG after two reductions due to persistent toxicity. Both UGT1A11/28 patients required dose adjustments: one with a 25% reduction and filgrastim prophylaxis, and another with a 75% dose. In contrast, neither of the UGT1A1*1/*1 patients required dose modification.Conclusions:This real-world series suggests that the UGT1A1*28 genotype is associated with a higher risk of severe toxicity, hospitalization, and dose modification in SG-treated patients. Although one UGT1A1*1/*1 patient also experienced severe toxicity, most serious events occurred in UGT1A1*28 carriers. Given the low cost of genotyping, implementing preemptive UGT1A1*28 testing prior to SG initiation may be a cost-effective strategy to anticipate and reduce serious adverse events. Prospective studies with larger cohorts are needed to confirm these findings.

A. Nishikawa¹, K. Narui¹, Y. Fujiwara², Y. Shibata¹, S. Adachi¹, K. Kawashima², M. Oshi², A. Yamada², H. Yoshikata³, T. Tsuburai³, I. Endo²; ¹Surgical Oncology, Yokohama City Univ. Medical Center, Yokohama, JAPAN, ²Surgical Oncology, Yokohama City University Graduate School of Medicine, Yokohama, JAPAN, ³Gynecology, Yoshikata Clinic, Yokohama, JAPAN.

Background: Systemic therapies for breast cancer (BC) can lead to cancer treatment-induced bone loss (CTIBL), increase fracture risk, impair the quality of life, and potentially worsen prognosis. Although CTIBL prevention has been established in postmenopausal patients with BC, CTIBL in premenopausal women remains unclear owing to the limited number of reports. Chemotherapy often induces ovarian suppression and estrogen deficiency, thereby accelerating bone loss. Furthermore, the effects of tamoxifen on the bone are yet to be established in premenopausal patients with BC. In this study, we prospectively evaluated CTIBL in premenopausal patients with BC by monitoring bone mineral density (BMD), hormones, and bone turnover markers. Methods: We recruited 64 premenopausal females diagnosed with early-stage BC. We compared patients receiving tamoxifen monotherapy (T group, n=19; median age, 45 [range, 37-55] years) with those receiving chemotherapy followed by tamoxifen therapy (C group, n=31; median age, 45 years [range, 31-50] years). BMD at the lumbar spine and femoral neck was measured at baseline, immediately after chemotherapy (C group), and at 6, 12, and 18 months after tamoxifen initiation. Serum levels of estradiol (E2), follicle-stimulating hormone (FSH), bone turnover markers, procollagen type 1 N-terminal propeptide (P1NP), tartrate-resistant acid phosphatase 5b (TRACP-5b), and undercarboxylated osteocalcin (ucOC) were concurrently assessed to evaluate hormonal and metabolic effects on bone health. Results: 1. BMD Changes: T group: The changes(±SD) in BMD were minimal, with a 2.2±5.1% decrease (p=0.13) at the lumbar spine and a 1.6±4.4% increase(p=0.19) at the femoral neck at 24 months.C group: Lumbar spine BMD decreased by 2.4±3.9% post-chemotherapy (p=0.0057) and by 3.4±3.1% at 24 months (p=0.0060). Femoral neck BMD decreased by 1.3±4.6% post-chemotherapy (p=0.24) and 4.1±4.1% at 24 months (p=0.0047). 2. Hormonal Changes: T group: E2 increased by 328.1±385.6% at 6 months (p=0.003) but returned to baseline by 24 months. FSH levels showed no significant changes.C group: E2 decreased by 76.2±49.6% post-chemotherapy (p<0.001), with no significant differences observed at 24 months. FSH increased by 1061.1±890.7% post-chemotherapy (p<0.001), gradually decreased, and remained 53.6±89.8% above baseline at 24 months (p=0.038). 3. Bone Turnover Markers: T group: P1NP and TRACP-5b levels showed no significant changes over 24 months (all p > 0.05). ucOC decreased by 22.6±36.5% at 6 months (p=0.036), stabilizing thereafter.C group: P1NP increased by 98.9±90.0% post-chemotherapy (p<0.001) and gradually returned to baseline levels by 24 months (-5.4±45.0%, p=0.90). TRACP-5b increased by 89.9±106.6% post-chemotherapy (p<0.001) and gradually returned to baseline levels by 24 months (5.7±44.3%, p=0.38). ucOC decreased by 82.6±11.5% post-chemotherapy (p<0.001) and remained suppressed, with no significant recovery observed at 24 months (-89.1±9.2%, p<0.001). Conclusions: The C group showed significant and sustained reductions in BMD. The observed bone loss could be attributed to chemotherapy-induced ovarian suppression and estrogen deficiency. Increased bone turnover markers were consistent with a high bone resorption state and bone loss. Conversely, BMD was preserved in the T group, consistent with stable hormone levels and bone turnover markers. These findings indicate the need for proactive bone health management, including regular BMD monitoring and consideration of bone-protective treatments, especially in premenopausal patients with BC receiving chemotherapy, to improve long-term quality of life without fracture.

N. Jahan¹, E. Sringer-Reasor¹, H. Sarfraz¹, K. Khoury¹, M. Escobar¹, C. P. Williams², I. Starks¹, T. Padalkar¹, S. Olisakwe¹, N. Henderson¹, S. A. Ingram¹, A. Azuero³, K. Keene⁴, M. E. Melisko⁵, E. H. Shinn⁶, G. B. Rocque¹; ¹Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, ²Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, ³UAB School of Nursing, University of Alabama at Birmingham, Birmingham, AL, ⁴Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, ⁵Division of Hematology and Oncology, University of California San Francisco, San Francisco, CA, ⁶Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX.

Background: Metastatic breast cancer (MBC) and its therapies can cause sexual problems, leading to distress and relationship problems. Unfortunately, limited information is available on acceptable interventions to address sexual problems in women with MBC. Methods: This qualitative study focuses on acceptable interventions for sexual problems of women with MBC. A medical anthropologist conducted semi-structured interviews with women diagnosed with MBC at the University of Alabama at Birmingham. Interviews were transcribed verbatim and inductively coded to identify recurring themes and exemplary quotes. Results: Between September 2024 and May 2025, 20 women aged 30-77 with MBC participated in interviews. Of 20, 11 (55%) were White and 9 (45%) were African American; 95% were heterosexual and 1 (5%) was bisexual; 10 (50%) were married or partnered and 10 (50%) were widowed, single, or divorced; and 90% were in menopause (natural or treatment-related). Participants expressed key intervention preferences reflecting both favorable views and concerns (Table). The most common interventions discussed were lubricants during sexual intercourse. Most patients expressed positive experiences with using lubricants, which provided a degree of symptom relief. However, some women expressed concerns about a burning sensation associated with lubricants. The second category was sex toys, including mostly different types of vibrators. Although the majority of the women expressed positive experiences about using sex toys, some expressed hesitancy. A third intervention discussed was hormonal vaginal preparations. Many women expressed concerns about the long-term side effects of using estrogen- or testosterone-containing vaginal preparations resulting in a limited willingness to use. Another intervention discussed was non-hormonal vaginal moisturizers, which they perceived as having limited benefits. Although a few women were open to using medications to improve sexual desire, the majority are hesitant due to potential side effects and an additional pill burden. The majority of women in relationships adopt or are willing to adopt changes beyond sex to improve communication, relationships, and intimacy. However, women were reluctant to use formal therapy, including couple and behavioral therapy, due to lack of time, other priorities, and skepticism about their effectiveness. Conclusions: This study identifies acceptable interventions to address the sexual problems of women with MBC. Over-the-counter interventions such as lubricants, sex toys, and behavioral techniques were preferred. They were more reluctant to use prescription medications such as estrogen- or testosterone-containing vaginal preparations, medications to enhance sexual desire, and formal couple and behavioral therapies due to concerns about side effects, skepticism about their effectiveness, and additional therapeutic burdens.

K. Doshi¹, S. Afridi², N. Iyer³, S. A. Haddad⁴; ¹Department of Hospice and Palliative Medicine, UT San Antonio Health Center/Mays Cancer Center, San Antonio, TX, ²Department of Internal Medicine, SUNY Upstate Medical Center, Syracuse, NY, ³Department of Internal Medicine, Loyola University Health Center- MacNeal Hospital, Berwyn, IL, ⁴Department of Hematology and Oncology, UT San Antonio Health Center/Mays Cancer Center, San Antonio, TX.

Background:Postmastectomy lymphedema remains a significant source of morbidity in breast cancer survivors. Physical therapy (PT) and occupational therapy (OT) are commonly employed for prevention and management, but optimal referral timing remains unclear. We evaluated whether early PT and OT referral after mastectomy reduces two-year lymphedema. Methods: We conducted a retrospective cohort study using the TriNetX Global Collaborative Network, which includes de-identified electronic health records from 151 healthcare organizations worldwide. We identified adult women (≥18 years) with a diagnosis of breast cancer (ICD-10: C50) who underwent mastectomy between January 1, 2000, and December 31, 2020. Patients with pre-existing lymphedema or hereditary lymphedema were excluded. Two cohorts were defined based on the timing of PT and OT initiation relative to the mastectomy date: Early cohort: PT/OT initiated within 14 days post-mastectomy (n = 5,197) and delayed cohort: PT/OT initiated more than 14 days post-mastectomy (n = 18,817). PT/OT procedures were identified using relevant CPT codes for therapy evaluations, manual lymphatic drainage, gait training, and self-care training. The primary outcome was the incidence of lymphedema occurring between 90 and 1095 days following the index event. A Cox proportional hazards model was used to assess the association between timing of PT/OT and lymphedema risk, adjusting for age, extent of breast resection, axillary dissection, and sentinel lymph node biopsy. Results In the multivariable Cox model, early initiation of PT/OT within 14 days post-mastectomy was significantly associated with reduced lymphedema risk (HR 0.737, 95% CI 0.608-0.893, p=0.002). Sentinel lymph node biopsy was associated with a protective effect (HR 0.721, 95% CI 0.546-0.953, p=0.021). In contrast, axillary lymph node dissection was associated with more than a twofold increased risk of lymphedema (right: HR 2.217, p=0.001; left: HR 2.101, p=0.002). Bilateral mastectomy was also protective (HR 0.597, p<0.001), and increasing age was modestly protective (HR 0.981 per year, p<0.001). Unilateral breast resections were not significantly associated with lymphedema risk. Conclusion Early initiation of PT/OT and the use of sentinel lymph node biopsy were independently associated with reduced lymphedema risk following mastectomy. In contrast, axillary lymph node dissection was strongly predictive of increased lymphedema risk. These real-world findings support current American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network (NCCN) guidelines advocating early rehabilitation and limited axillary surgery to minimize long-term morbidity in breast cancer survivors.

C. Smith¹, M. Layoun², H. Li³, E. Koltner³, M. T. Imboden³, Z. Taylor², K. J. Spinelli³, D. Page¹; ¹Providence Cancer Institute, Providence Portland Medical Center, Portland, OR, ²Providence Heart Institute, Providence St Vincent Medical Center, Portland, OR, ³Center for Cardiovascular Analytics, Research + Data Science (CARDS), Providence St Vincent Medical Center, Portland, OR.

Background: Incidences of cardiotoxicity related to HER2-directed antibody therapy (anti-HER2) vary considerably from 0.5% to 30% depending on comorbidities and chemotherapy regimen. Recent studies have posited whether low-risk cohorts could decrease or eliminate surveillance echocardiography given low incidences of treatment-related heart failure (HF). Objectives: The aim of this study was to characterize the incidence of cardiotoxicity in patients receiving HER2-therapies, evaluate predictors of cardiotoxicity, and examine the incidence of LVEF decline and new HF among a low-risk subgroup. Methods: We performed a retrospective cohort study of early stage (I-III) breast cancer patients who received anti-HER2 between 1/1/2016-3/20/2024 and completed baseline and surveillance echocardiography in the 7-state Providence healthcare network. The primary outcome was development of LVEF ≤50% during anti-HER2. Secondary outcomes included new HF diagnosis (based on ICD-10 codes I50.x), any hospitalization, and all-cause mortality. Incidences of LVEF ≤50% and new HF were also obtained in a low-risk subgroup. Logistic regression models accounting for demographics, comorbidities, HER2 treatment regimen, and preceding cardiac medications were performed.Results: The study included 1,215 patients (Table). Fifty-two patients (4%) developed LVEF ≤50% during anti-HER2. Among this subset, 52% were hospitalized and 42% had a new HF diagnosis during the treatment period. No patients died while receiving anti-HER2 or during 1-year follow up. Univariate modeling revealed that CAD (aOR [95% CI] = 3.22 [1.21, 8.61]) and prior HF (aOR [95% CI] = 3.67 [1.23-10.99]) were associated with treatment-related LVEF ≤50%, though no comorbidities were predictive on multivariate analysis. After risk adjustment, HER2 treatment regimen was the only predictor of LVEF ≤50% during therapy (taxanes + platinum vs. anthracyclines: aOR [95% CI] = 0.22 [0.10, 0.48]; taxanes vs. anthracyclines: aOR [95% CI] = 0.29 [0.13, 0.65]. New HF was observed in 11% of patients receiving anthracyclines compared to 4-5% in other treatment arms (p = 0.024). Patients deemed low-risk (non-anthracycline regimen, no prior CAD or HF) developed an LVEF ≤50% in 3.3% of patients and new HF in 2.6% of patients. Conclusions: In a real-world clinical setting, anti-HER2-associated LVEF declines were uncommon but were associated with increased hospitalizations and HF diagnoses. Exposure to anthracyclines was the only predictive risk factor for LVEF decline. Interim analysis of a low-risk cohort (non-anthracycline regimen, no prior CAD or HF) still demonstrated a modest incidence of LVEF decline and HF, suggesting that enhanced risk stratification should be considered before deferring echocardiographic surveillance in these subgroups.

P. S. Satheeshkumar¹, S. Panginikkode², V. Gopalakrishnan³, D. Kewlani⁴, N. Alam¹, T. Odemuyiwa⁵, R. Pili¹, P. Padhi⁵; ¹Internal Medicine-Division of hematology and oncology, University at Buffalo, Buffalo, NY, ²Department of Rheumatology, Tufts Medical Center, Boston, MA, ³Internal Medicine, University of Massachusetts, Worcester, MA, ⁴Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, ⁵Internal Medicine-Division of hematology and oncology, University at Buffalo, Williamsville, NY.

AIM AND OBJECTIVES: Analyzing IrAEs data provides an opportunity to investigate the impacts of targeted therapy, especially as the implementation of immunotherapy in breast cancer has enhanced survival rates. We utilized digital tools to illustrate that IrAEs, including characteristics, are essential to manage for cancer patients receiving treatment, and identifying outcomes and disparities is significantly more critical. METHODS: We examined breast cancer patients admitted to the hospital in the year 2021 (National Inpatient Sample database) and further examined IrAEs among them. IrAEs examined included dermatologic, endocrine, gastrointestinal, hepatic, neurologic, pancreatic, pulmonary, and renal. We utilized approaches—propensity score matching (PSM) and difference-in-difference (DID), and additional PSM DID combined and further multivariable generalized linear models accounting for weights—to examine the outcomes—mortality, infectious complications (mainly septicemias and healthcare-associated complications), and complicated diabetes (diabc), complicated hypertension (hypc), fluid and electrolyte disorders (fed), and depression (depre) were examined. And additionally, we examined the disparities in the outcomes. RESULTS: We examined 108,170 breast cancer patients admitted to the hospital in the year 2021, and we further observed 28,390 (26%) IrAEs among them. The mean [SD] age of the patients admitted to the hospital with IrAEs was 66 [13.25] years. The breast cancer patients who reported with IrAEs were associated with higher odds of mortality (aOR: 1.18, 95% CI: 1.02-1.38). Compared to the high-income group, the low-income group was associated with higher mortality (1.26; 1.02-1.56). And further, those with IrAEs were associated with higher septicemias (1.33; 1.21-1.46). Compared to Whites, Blacks (1.06; 1.05-1.45), Hispanics (1.26; 1.05-1.45), and Native Americans and Others (1.26; 1.07-1.48) were associated with higher septicemias. And compared to high-income neighborhoods, low-income neighborhoods were associated with higher septicemias (aOR: 1.16; 95% CI 1.03-1.32). Similarly, the trend of IrAEs outcomes and disparities was examined among fluid and electrolyte disorders(1.66; 1.07-1.27), hypertension (1.16; 1.07-1.27), and depression (1.48; 1.36-1.6). Disparities observed (Blacks were having higher hypertension, and depression was higher among Whites compared to all other racial groups, and fed was higher among low-income groups) were examined. We additionally evaluated the impact of IRAES on individual outcomes using PSM DID. The treatment effect (TE) and the average treatment effect (ATE) were examined as specific metrics that measure the average causal influence of a treatment across breast cancer cohorts. CONCLUSION: Investigating the IrAEs in breast cancer patients is crucial, since the five-year survival rate for these patients is key for patient treatment. Consequently, the competing risks within this population are particularly significant to identify, as they fall under this framework. This marks the inaugural application of digital health techniques to investigate inequities. Black individuals, Native Americans, and low-income communities are disproportionately impacted by the new regimes.

J. Hill¹, B. Kielkowski¹, S. Nolfi², C. Marino², L. Thomas²; ¹Pharmacy, West Virginia University Cancer Institute, Morgantown, WV, ²Hematology/Oncology, West Virginia University Cancer Institute, Morgantown, WV.

Background: Ribociclib, a CDK4/6 inhibitor, is widely used in hormone receptor-positive, HER2-negative breast cancer. While hepatotoxicity is a known adverse event associated with ribociclib, its real-world incidence and characteristics may differ from those observed in clinical trials. This study aimed to evaluate the incidence, severity, and clinical course of hepatotoxicity in patients receiving ribociclib in routine clinical practice. Methods: We conducted a retrospective chart review of 90 patients treated with ribociclib at our institution. Patients who received fewer than 14 days of treatment (n=25) were excluded, leaving 65 patients for analysis. We assessed liver function test abnormalities during treatment and graded hepatotoxicity according to CTCAE v5.0 criteria. Data on baseline liver disease, liver metastases, concurrent hepatotoxic medications, and CYP3A4 inhibitors were collected. Results: Among the 65 patients included, 10 (15.4%) developed grade 3-4 hepatotoxicity: 5 patients (7.7%) with grade 3 and 5 patients (7.7%) with grade 4. The observed incidence of grade 4 hepatotoxicity was approximately three-fold higher than reported in pivotal ribociclib clinical trials, including MONALEESA-2, MONALEESA-3, MONALEESA-7, and NATALEE, where incidence of grade 4 hepatotoxicity ranged from 0.9-2.5%.^1-4 Notably, only 2 of the 10 patients had baseline liver metastases, and just 1 patient had known baseline liver disease (hepatic steatosis). None of the patients who experienced grade 3-4 hepatotoxicity were receiving strong CYP3A4 inhibitors or other hepatotoxic medications at the time of onset. The median time to onset of hepatotoxicity was 15 weeks (range: 2-29 weeks), and the median time to recovery was 11 weeks (range: 4-30 weeks). Among the 5 patients who developed grade 3 hepatotoxicity, 3 were rechallenged with a reduced dose of ribociclib. All three patients experienced recurrent hepatotoxicity following rechallenge. Conclusions: In this real-world cohort, the incidence of grade 4 hepatotoxicity with ribociclib was significantly higher than reported in clinical trials, underscoring the importance of vigilant hepatic monitoring beyond trial conditions. Hepatotoxicity occurred independently of baseline liver metastases, pre-existing liver disease, or concurrent use of known hepatotoxic agents. Rechallenge following grade 3 hepatotoxicity was associated with recurrence, suggesting cautious consideration before re-initiation. These findings highlight the need for personalized risk assessment and further investigation into predictors of severe hepatotoxicity in patients treated with ribociclib. References Hortobagyi GN, Stemmer SM, Burris HA, et al. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. N Engl J Med 2022;386(10):942-950. Slamon DJ, Neven P, Chia S, et al. Phase III randomized study of ribociclib and fulvestrant in hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: MONALEESA-3. J Clin Oncol 2018;36:2465-2472. Lu YS, Im SA, Colleoni M, et al. Updated Overall Survival of Ribociclib plus Endocrine Therapy versus Endocrine Therapy Alone in Pre- and Perimenopausal Patients with HR+/HER2- Advanced Breast Cancer in MONALEESA-7: A Phase III Randomized Clinical Trial. Clin Canc Res 2022;28(5):851-859. Slamon DJ, Lipatov O, Nowecki Z, et al. Ribociclib plus Endocrine Therapy in Early Breast Cancer. N Engl J Med 2024;390(12):1080-1091.

E. M. Grannan¹, A. C. McGhie¹, A. Zheng¹, S. Cherian¹, A. B. Newman², R. M. Layman³, S. Damodaran³; ¹Division of Pharmacy, MD Anderson Cancer Center, Houston, TX, ²Cancer Medicine, MD Anderson Cancer Center, Houston, TX, ³Breast Medical Oncology, MD Anderson Cancer Center, Houston, TX.

Background: Currently multiple biosimilars of trastuzumab (Herceptin®) are approved for use in HER2-positive breast cancers. Accordingly, MD Anderson Cancer Center updated its formulary from trastuzumab (Herceptin®) to trastuzumab biosimilars: trastuzumab-qyyp (Trazimera®) and trastuzumab-anns (Kanjinti®), with trastuzumab-qyyp designated as the preferred agent. While these biosimilars have been approved based on extensive structural and functional characterization demonstrating similar clinical activity, differences in hypersensitivity reactions (HSRs) have been reported. We evaluated the incidence of HSRs in patients receiving trastuzumab biosimilars compared to the reference product. Methods: A retrospective chart review was conducted on patients who received trastuzumab products from January 1, 2019, to January 1, 2025. Patients with documented trastuzumab allergies in EMR were included in this analysis. Incidence of HSR between patients who received trastuzumab (Group A, n=612) and trastuzumab biosimilars (Group B, n=503) was compared. Results: HSRs were significantly more common in patients in patients who received trastuzumab biosimilars (Group B; n=86, 17.1%) compared to trastuzumab (Group A; n=22, 3.6%) (p<0.001). Majority of the patients in Group B received Trastuzumab-qyyp (n=79, 92%). Chills and/or rigors were the most common HSR symptom across both groups (Group A: n=18, 75%); Group B: n=75, 87.2%). Severe symptoms, such as dyspnea (Group A: n=2 [9.1%] vs Group B: n=10 [11.6%], p=0.74) and hypotension (Group A: n=1, [4.5%] vs Group B: n=5 [5.8%], p=0.82), were not significantly different between the groups. Two patients in Group B required epinephrine, while no patients in Group A required epinephrine. Seven patients in Group B required a change in trastuzumab product. Conclusion: The incidence and severity of HSRs were higher in patients receiving biosimilar trastuzumab products compared to the reference product. Data collection for patients without documented trastuzumab allergies is ongoing. Based on this analysis, a prospective study utilizing prophylactic medications is being planned.

F. li¹, J. Li¹, X. Chen²; ¹Department of Oncology, The Second Affiliated Hospital of Anhui Medical University, hefei, CHINA, ²Department of Neurology, The First Affiliated Hospital of Anhui Medical University, hefei, CHINA.

Background: Cognitive impairments, particularly in attention, are frequently reported among breast cancer survivors undergoing systemic anticancer therapies. However, the changes across distinct attention functions remain poorly characterized. This study aims to investigate alterations in the attention networks among breast cancer survivors treated with chemotherapy and tamoxifen and to explore their association with treatment duration. Methods: Between September 2018 and December 2024, a total of 435 breast cancer survivors who underwent chemotherapy followed by tamoxifen treatment, along with 242 age-matched healthy female controls were recruited. The Attention Network Test was utilized to assess the efficiency of attentional networks. Linear regression and restricted cubic spline analyses were employed to evaluate changes in the three attention networks among breast cancer survivors. Results: Compared with healthy controls, breast cancer survivors exhibited significantly reduced efficiency in the alerting (P < .001) and executive (P < .001) networks, while the orienting network efficiency remained intact. Notably, the executive network demonstrated a nonlinear (V-shaped) trajectory over treatment duration, characterized by an initial improvement peaking around at approximately 15 months, followed by a subsequent decline (nonlinear P < .001). This pattern was consistent across different chemotherapy subtypes. The alerting network showed persistent impairment throughout the five-year observation period (linear P = .247), potentially indicative of underlying neural alterations. Conclusions: Systemic anticancer treatments in breast cancer survivors are associated with selective impairments in attention networks, characterized by deficits in alerting efficiency and a V-shaped trajectory of executive function changes over a five-year period. These findings suggest that early chemotherapy-related cognitive effects may be transient, whereas prolonged tamoxifen use could contribute to persistent executive dysfunction. Longitudinal studies are essential to elucidate the underlying causal mechanisms and inform strategies for cognitive rehabilitation. Keywords: Breast cancer; Chemotherapy; Tamoxifen; Cognitive function; Attention network

M. Wang¹, M. Huang², X. Zhao³, H. Che⁴, J. Li¹, M. Cheng⁵, S. Aili⁶, X. Zhao⁷, X. Wang⁸, Y. Zou⁹, H. Wang¹; ¹Breast Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliate Cancer Hospital Of University Of Electronic Science and Technology of China (UESTC), ChengDu, CHINA, ²Breast Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, CHINA, ³Thyroid Breast Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong, CHINA, ⁴Thyroid Breast Surgery, Zigong First People’s Hospital, Zigong, CHINA, ⁵Breast and thyroid surgery, Suining Central Hospital, Suining, CHINA, ⁶Thyroid Breast Surgery, Guangyuan Central Hospital, Guangyuan, CHINA, ⁷Breast and thyroid surgery, Leshan People’s Hospital, Leshan, CHINA, ⁸Oncology, Neijiang Second People’s Hospital, Neijiang, CHINA, ⁹Breast and thyroid surgery, Dazhou Central Hospital, Dazhou, CHINA.

Background: Trastuzumab Emtansine (T-DM1), an antibody-drug conjugate of trastuzumab and emtansine, is an established adjuvant or second-line therapy for HER2-positive breast cancer (BC), widely used in China for both early-stage and advanced HER2-positive BC. Thrombocytopenia represents a common adverse event associated with T-DM1 in Chinese patients, with the incidence of grade ≥3 thrombocytopenia reported as 40.4% in the ELAINA study. This study was designed to investigate the impact of T-DM1 with dose escalation on thrombocytopenia incidence. Method: This multicenter, retrospective study enrolled HER2-positive BC patients treated with T-DM1 between May 2024 and March 2025, all of whom had received at least one prior systemic therapy. Patients were stratified into two cohorts: (1) early-stage disease with residual disease (non-pCR) post-neoadjuvant therapy; (2) advanced-stage disease with progression following prior systemic treatments. T-DM1 dose was escalated in a stepwise manner: 2.4 mg/kg administered in Cycle 1, followed by 3.0 mg/kg in Cycle 2, and culminating in 3.6 mg/kg in Cycle 3. Safety was closely monitored at each dose level, especially for thrombocytopenia. Non-pCR patients received up to 14 cycles of T-DM1, while those with advanced-stage continued treatment until disease progression or unacceptable toxicity. The primary outcome was thrombocytopenia incidence. Data on treatment patterns, adverse events, and clinical efficacy were also collected and analyzed. Result: A total of 46 patients were included (37 non-pCR; 9 advanced). The mean age was 52.8±8.9 years. Five patients (10.9%) with visceral crisis were all in advanced-stage. Prior systemic therapy was reported in all patients. All 37 non-pCR patients received neoadjuvant chemotherapy: 78.4% platinum-based, 13.5% anthracycline-based, and 8.1% other regimens. For advanced breast cancer, Seven and 2 patients received T-DM1 as first and later-line therapy, respectively. The initial dose of all the patients was 2.4 mg/kg. Maximum dose levels were 2.4 mg/kg in 39.1%, 3.0 mg/kg in 17.4%, and 3.6 mg/kg in 43.5% of patients, respectively. The median treatment duration was 75 days (range 7-377). Overall, 4 patients (8.7%) discontinued T-DM1: 3 patients (6.5%) due to disease progression and 1 patient (2.2%) as per physician’s advice (unrelated to thrombocytopenia). Thrombocytopenia of any grade occurred in 58.7% of patients, while grade ≥3 thrombocytopenia was observed in 30.4% of patients. Thrombocytopenia of any grade occurred with a median onset of 8 days, while grade ≥3 thrombocytopenia occurred with a median onset of 280 days. Conclusion: T-DM1 dose escalation was well tolerated and effective with a relatively low incidence of grade ≥3 thrombocytopenia. Further prospective studies are warranted to confirm the benefit of initial low-dose T-DM1.

L. Medina¹, V. Barghout¹, R. L. Best¹, J. Patten-Coble², T. Buckingham³, H. Hammond³, C. Hogea³; ¹n/a, Viver Health, Morristown, NJ, ²n/a, Little Pink Houses of Hope, Burlington, NC, ³Patient-Focused Implementation Sciences, Gilead Sciences, Inc., Foster City, CA.

Background: Metastatic breast cancer (MBC) is breast cancer that has spread beyond the breast and regional lymph nodes. For MBC, treatment goals are typically controlling disease progression and maintaining quality of life (QoL). However, disease-related symptoms and treatment-related side effects often impair QoL and may result in decreased treatment adherence. Treatment-related side effects are among the leading reasons patients with MBC discontinue recommended therapy. There is an urgent need for evidence-based tools that inform and empower patients to effectively manage symptoms and treatment-related side effects, optimize their QoL, and facilitate informed patient-provider communication. Methods: We used a qualitative stakeholder-informed approach with literature review and iterative resource creation to identify gaps in patient education, symptom management, and shared decision-making in MBC. This review informed the IRB-approved protocol and discussion guide for semi-structured interviews held with US individuals living with MBC (n=9; from rural and urban areas and diverse racial and ethnic backgrounds (Asian, Black, White—Hispanic and non-Hispanic))and the healthcare providers (HCPs) who treat them (n=4). Interview findings guided the co-creation of a printed symptom management resource, Your Guide to Managing Symptoms from Metastatic Breast Cancer Treatment, focused on the topics participants identified as most needed. The same participants reviewed the Guide for understandability, clarity, and usability. The Guide underwent medical review for accuracy and alignment with clinical guidelines and received endorsement by the Academy of Oncology Nurse & Patient Navigators (AONN+). An online survey was created to track usage and assess satisfaction, behavior change, and reach. Results: Individuals reported struggling with the mental and emotional symptoms of MBC, navigating available support resources, and managing therapy side effects—including fatigue (100%), pain (67%), neutropenia, and digestive issues (100%). Our results underscored the unmet need for a patient-focused educational resource to support symptom management and provider-patient communication. The resulting resource, Your Guide to Managing Symptoms from Metastatic Breast Cancer Treatment, is an accordion-style four-fold printed handout backed by 142 references. Based on interview findings, it focuses on evidence-based whole-person interventions to help manage symptoms and side effects and enhance patients’ QoL. It includes integrative strategies and resources to manage physical, emotional, nutritional, and financial concerns, including managing fatigue, treatment-related side effects, and cost-of-care resources. HCPs described it as “timesaving” and engaging, with one noting, “The fatigue panel should be given to everyone.” Patients appreciated its practical actionable tools, stating, “[it’s] very empowering, allows people to do something.” Preliminary feedback indicated greater confidence in managing symptoms, increased resource awareness, and greater participation in shared decision-making with HCPs. Patients rated the use likelihood as extremely likely (10/10). Conclusions: Your Guide to Managing Symptoms from Metastatic Breast Cancer Treatment fills key gaps in patient disease state and financial support education, symptom management, and shared decision-making for those living with MBC. By integrating evidence-based co-created content with stakeholder insights, the Guide offers a practical accessible tool for whole-person care. Early feedback suggests it enhances patient confidence, promotes meaningful dialogue with HCPs, and may contribute to improved QoL. Ongoing usage and impact evaluation will inform future resource development and dissemination.

H. Moore¹, A. Kupper¹, R. Bansal², C. Anders², J. Burrows³, P. Alice³, A. Erkanli³; ¹Pharmacy, Duke Cancer Institute, Durham, NC, ²Medicine, Duke Cancer Institute, Durham, NC, ³Biostatistics and Informtics, Duke Cancer Institute, Durham, NC.

BackgroundTrastuzumab deruxtecan (T-DXd) is a highly effective antibody-drug conjugate (ADC) indicated for the treatment for metastatic, HER2-positive or HER2-low/ultra-low, breast cancer (MBC) with objective response rates between 50-80% as reported within DESTINY-BREAST01, -03, -04, and -06. Despite its efficacy, T-DXd carries a black box warning for interstitial lung disease (ILD)/pneumonitis with approximately 10-15% risk of ILD development including some grade (G) 5 events. Given G2-4 ILD result in permanent discontinuation of T-DXd, identifying ILD earlier at G1 is essential to maintain therapy; however, monitoring guidance remains limited and variable amongst individual practice. The tumor microenvironment (TME) plays an important role in CNS tumor growth as cancerous cells create complex relationships that reorganize the local TME and reprogram CNS cells, including lymphocytes. It is not yet known if an association exists between patients (pts) with brain metastases (BrM) and decreased total lymphocyte counts and an increased risk of developing opportunistic infections (OI) and/or T-DXd-related ILD. However, the DESTINY-Breast12 study suggested potentially higher rates of ILD in pts with BrM than in pts without and 5 pts in the BrM group concurrently developed an OI. As T-DXd use continues to extend across other tumor types, identifying risk factors (RF) that may increase ILD risk as well as improved monitoring strategies is essential. This retrospective study aims to assess the incidence of ILD and OI, associated RF, monitoring strategies, and management of T-DXd-related ILD in MBC with BrM or leptomeningeal diseases (LMD) as well as assess any correlation with lymphocyte depletion. MethodsThis is a single-center, retrospective, cohort study in pts with MBC with BrM and/or LMD at the Duke Cancer Institute (DCI) Center from 12/2019 to 9/2024. Eligible pts were ≥18 years of age with a diagnosis of HER2 ultra-low/low/positive MBC with BrM and/or LMD receiving T-DXd, with or without additional ILD monitoring to include CT-ILD or standard restaging (PET or CT). ResultsA total of 36 pts with HER2-ultra low, low or positive MBC who had received T-DXd were included. A total of 23 pts had HR+ MBC, and 6 pts with TNBC. Approximately 36 pts and 6 pts had BrM and LMD, respectively. In the study cohort, 7 pts (19.4%; 95% CI 8.2%, 36%) developed ILD. One pt had G1 ILD, 5 pts had G2 ILD, and 1 pt had G3 ILD. Among pts who developed ILD, the average time from start of T-DXd treatment to ILD onset was 7.3 (range: 0.3-15.4) months. All 7 pts with confirmed ILD were treated with corticosteroids. Of pts who had a decreased lymphocyte count at the time of cycle 1 day 1 of T-DXd treatment, 4/15 (26.7%) developed ILD. Among pts with a history of smoking tobacco and pts with no history of smoking tobacco, 3/12 (25.0%) and 4/24 (16.7%) developed ILD, respectively. Among pts < 60 yo and pts ≥60 yo, 4/20 (20.0%) and 3/16 (18.8%) developed ILD, respectively. No pts in the study cohort had a history of COPD, ILD, or CKD. Two pts developed an OI while on treatment with T-DXd (5.6%). One pt who developed an OI did not develop ILD while one pt did develop ILD. Additional results to be presented with increased sample size and ILD monitoring strategy. ConclusionA numerically higher rate of ILD was observed in pts with BrM and/or LMD compared to rates previously reported. The results of this study do not suggest an association between the RF assessed and T-DXd-related ILD, however, this may be due to the small sample size. Further investigation is needed to determine if pts with BrM and/or LMD may be at an increased risk of OI or ILD, however, 26.7% of pts with a decreased lymphocyte count at T-DXd initiation developed ILD, suggesting a potential correlation.

S. Jaman¹, J. Jaman², T. Tokic³, I. Todoric³, L. Trkmic³, M. Krizic¹, K. Cular¹, T. Silovski¹; ¹Department of Oncology, University Hospital Center Zagreb, Zagreb, CROATIA, ²Department of Plastic, Reconstructive and Aesthetic Surgery, Dubrava University Hospital, Zagreb, CROATIA, ³School of Medicine, School of Medicine, University of Zagreb, Zagreb, CROATIA.

Predictors of Medication-related Osteonecrosis of the Jaw in HR+/HER2- Metastatic Breast Cancer Patients Treated with CDK4/6 Inhibitors Background: Hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+/HER2-) metastatic breast cancer (mBC) represents 60-70% of all mBC, with bones being the most common site of metastases in ~60% of cases. Combination of endocrine therapy (ET) and cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) is the standard treatment in HR+/HER2- mBC with addition of antiresorptive therapy (ART) in cases of bone metastases. ART implies application of parenteral or peroral bisphosphonates as well as denosumab. Medication-related osteonecrosis of the jaw (MRONJ) is a known side effect of all ART. This study aimed to assess the incidence and predictors of MRONJ in HR+/HER2− mBC patients receiving CDK4/6 inhibitors and ART, with emphasis on treatment type, duration, and cumulative dose. Methods: A retrospective cohort of 193 female patients with HR+/HER2− mBC treated with CDK4/6i (ribociclib, palbociclib, abemaciclib) and ART (zoledronate, ibandronate, denosumab, clodronate and pamidronate) in the University Hospital Center Zagreb was analyzed with prior Ethics Committee approval. Descriptive statistics, group comparisons, and logistic regression models were used to identify clinical and treatment-related predictors of MRONJ. Results: MRONJ was developed in 14 out of 193 patients (7.3%), who were significantly older (71.6 ± 8.0 vs. 63.8 ± 13.8 years; p = 0.0039) and had longer CDK4/6i exposure (median 48.0 vs. 22.0 months; p = 0.047). MRONJ incidence was higher in patients treated with abemaciclib (13.0%) and ribociclib (9.9%) than with palbociclib (2.5%), though this difference did not reach statistical significance (p = 0.0952). Among 193 patients receiving ART, most commonly used ART agents were zoledronic acid in 104 patients (53.9%), followed by ibandronate in 71 patients (36.8%) and denosumab in 18 patients (9.3%). Among the 14 patients who developed MRONJ, 8 (57.1%) had received zoledronic acid, 4 (28.6%) ibandronate, and 2 (14.3%) denosumab. Adjusted cumulative ART doses were calculated, and higher doses were observed in MRONJ compared to the non-MRONJ group (6266,85 mg vs 3848,8 mg respectively), without reaching statistical significance (p = 0.47). Total ART duration was significantly longer in the MRONJ group (52.71 vs. 33.98 months), with a p-value of 0.033. Conclusion: Older age and longer CDK4/6i exposure was associated with an increased risk of MRONJ in patients with HR+/HER2− mBC. Although MRONJ incidence appeared higher with abemaciclib and ribociclib compared to palbociclib, it did not reach statistical significance, possibly due to small numbers. These findings highlight the need for careful monitoring and risk assessment in patients undergoing long-term CDK4/6i therapy in combination with ART.

J. A. Glasby; Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA.

Introduction: Efbemalenograstim alfa, a non-PEGylated, long-acting, human granulocyte-colony stimulating factor was recently evaluated for the management of chemotherapy-induced neutropenia in a phase III trial of 393 patients with stage I-III invasive breast cancer. The study met the primary end point, demonstrating that a single dose of efbemalenograstim alfa was noninferior to pegfilgrastim, decreasing the duration of severe neutropenia in cycle 1. An additional endpoint of the phase III trial was the incidence of severe neutropenia (ISN; grade 4, ANC <0.5 × 10⁹/L) across all chemotherapy cycles, which demonstrated significant reductions in ISN at later cycles. Here, we aimed to investigate is these reductions in ISN in later chemotherapy cycles occurred in previous trials of efbemalenograstim alfa and with different chemotherapy regimens. Methods: ISN rates from four cycles from phase III trials of efbemalenograstim alfa and three different chemotherapy regimens, docetaxel + cyclophosphamide (TC) (Trial 1), epirubicin + cyclophosphamide (EC) (Trial 2), and high myelotoxic docetaxel + doxorubicin (TA) (Trial 3 + historic pegfilgrastim and filgrastim comparative data) were evaluated. Results: Trial 1 included 197 patients randomized to efbemalenograstim alfa, compared to 196 randomized to pegfilgrastim that received TC chemotherapy. During cycle 1, ISN for both groups was 11.7%, but for subsequent cycles, ISN was lower for patients that received efbemalenograstim alfa compared to pegfilgrastim, 4.6% vs 5.1% for cycle 2, 2.6% vs 6.3% for cycle 3 (p=0.08) and significantly lower, 1.6% vs 5.3% for cycle 4 (p=0.05), respectively. Trial 2 included 122 patients randomized to efbemalenograstim alfa, compared to 120 randomized to filgrastim that received EC chemotherapy. During cycle 1, ISN was 14.2% for the efbemalenograstim alfa, compared to 16.0% for the filgrastim groups, with subsequent cycles at 1.7% vs 0.9%, respectively, for cycle 2, significantly lower, 0% vs 3.9% for cycle 3 (p=0.048) and 1.8% vs 4.0% for cycle 4. Trial 3 included 83 patients randomized to efbemalenograstim alfa and 39 randomized to placebo, therefore ISN for the TA chemotherapy regimen was compared to a historic pegfilgrastim + TA and filgrastim + TA phase III trial data, which showed an ISN at cycle 1 of 69.9% for efbemalenograstim alfa and 77-84% for pegfilgrastim, and 79-83% for filgrastim. ISN at cycle 2 was 15% for efbemalenograstim alfa and much higher for pegfilgrastim 45-57% and filgrastim 54-55%, and similarly for cycle 3, 20%, 37-56% and 53-60% and cycle 4, 10%, 45-51% and 49-55%, respectively. Conclusion: Across studies, non-PEGylated efbemalenograstim alfa has demonstrated equivalent or lower incidence rates of severe neutropenia (grade 4, ANC <0.5 × 10⁹/L) during the first cycle of three types of chemotherapy (TC, EC and TA) and importantly, significantly lower rates in later cycles when compared to pegfilgrastim and filgrastim. These findings demonstrate that efbemalenograstim alfa may be more effective at preventing severe, life-threatening neutropenia at later chemotherapy cycles, which has meaningful implications for real-world breast cancer patients that are likely to receive chemotherapy for longer durations.

R. M. Borges¹, M. C. Gouveia¹, C. Giro¹, M. Aisen¹, L. C. Oliveira¹, N. J. Gomes², A. C. Ferrari³, T. G. Rivelli³, M. S. Neto³, M. L. Brito⁴, R. B. Sousa⁵, K. P. Sacardo⁶, B. M. Zucchetti¹; ¹Oncologia Clínica, Rede Américas, Hospital 9 de Julho, São Paulo, BRAZIL, ²Oncologia Clínica, Hospital São Domingos, São Luís-MA, BRAZIL, ³Oncologia Clínica, Rede Américas, Hospital Santa Paula, São Paulo, BRAZIL, ⁴Oncologia Clínica, DASA Oncology – Clínica AMO, Salvador-BA, BRAZIL, ⁵Oncologia Clínica, Brasília Hospital, Oncologia Américas, Brasilia, BRAZIL, ⁶Oncologia Clínica, Rede Américas, Hospital Christóvão da Gama, Santo André – SP, BRAZIL.

Introduction CDK4/6 inhibitors have significantly changed altered the natural history of HR+/HER2− metastatic breast cancer, leading to substantial improvements in progression-free and overall survival. These drugs are generally well tolerated, with manageable toxicity profiles. However, rare dermatologic adverse events may be underreported and poorly understood. In this study, we describe case series of patients who developed vitiligo-like lesions during treatment with ribociclib or abemaciclib. Case Series Description A total of eight women with HR+/HER2− metastatic breast cancer receiving ribociclib (n=7) or abemaciclib (n=1), all in combination with endocrine therapy (aromatase inhibitor or fulvestrant), developed well-demarcated depigmented lesions consistent with vitiligo-like lesions. None had a prior history of autoimmune or dermatologic disease. Dermatologic evaluations and lesion photographs were obtained. In two cases, skin biopsies revealed pigmentary incontinence and chronic perivascular mononuclear infiltrate.Cutaneous changes developed within a median of 8 months (minimum 6 and maximum 24 months) after treatment initiation. The lesions were asymptomatic, hypopigmented, and primarily involved the face, neck, and upper limbs. No systemic symptoms were reported. Dermatological evaluation ruled out other differential diagnoses and suggested an immune-mediated mechanism. In one patient, treatment was permanently discontinued after two years due to cutaneous toxicity from vitiligo-like lesions, with sustained oncologic response; another patient had a temporary 3-month drug interruption due to lesion worsening, after which the skin changes stabilized. All patients were treated with topical corticosteroids, resulting in partial improvement. Complete lesion regression was observed in the patient who discontinued therapy; three patients had stable lesions while continuing medication; others showed partial regression after treatment change due to disease progression. Discussion The most common skin toxicities associated with ribociclib and abemaciclib include rashes and dermatitis (10-20%). Vitiligo-like reactions are rare. CDK4/6 inhibitors may affect the proliferation of keratinocyte precursors, compromising the secretion of melanocyte-supporting cytokines. Treatment-induced melanocyte apoptosis may contribute to depigmentation. Additionally, ultraviolet radiation-induced melanocyte damage may trigger immune responses, highlighting the importance of sun protection. However, the underlying pathophysiology remains unclear. Conclusion This case series highlights a potentially underrecognized cutaneous adverse event associated with CDK4/6 inhibitors (ribociclib and abemaciclib). Oncologists should be aware of vitiligo-like reactions as part of the toxicity spectrum of these agents. It is important to point out that this is not a life-threatening condition but it can affect appearance, specially of the face, causing burden for patients. Early recognition and collaborative management with dermatology can allow continuation of cancer therapy without compromising treatment outcomes or quality of life. Further studies are needed to better understand this phenomenon.

S. Rosenfeld¹, O. Ajayi¹, R. Choksi², S. W. Champaloux³, D. Parris³, A. Rui³, A. Lamb³, M. Gart³, C. Wall³, B. Wang³, P. Varughese³, J. Donegan³, L. Morere³, R. Geller³, J. Scott³, V. Gorantla²; ¹Medical Oncology, Highlands Oncology Group (HOG), Fayetteville, AR, ²Medical Oncology, University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, ³PrecisionQ, IntegraConnect, West Palm Beach, FL.

Background: As of January 2023, the National Comprehensive Cancer Network (NCCN) guidelines recommend using combinations of 5HT3, NK1, olanzapine (O), and dexamethasone (DEX) drugs as prophylaxis with highly emetic therapies, including fam-trastuzumab deruxtecan-nxki (T-DXd). An IntegraConnect PrecisionQ multi-practice quality initiative was conducted with Highlands Oncology Group (HOG), University of Pittsburgh Medical Center (UPMC), and Regional Cancer Care Associates (RCCA) to assess adherence to recommended antiemetic use in HER2-positive (HER2+) and HER2-low metastatic breast cancer (mBC) patients (pts) treated with T-DXd. This initiative compared current practices to NCCN guidelines, identified potential gaps in care, and implemented strategies to address these gaps. Our goal was to demonstrate improvements in antiemetic utilization for mBC pts treated with T-DXd as a result of this quality initiative. Methods: Using the IntegraConnect PrecisionQ de-identified database, HER2+ and HER2-low pts treated with T-DXd were evaluated for specific time periods at each practice related to antiemetic utilization. HOG (baseline: 1/1/2022-12/31/2023 and follow-up: 01/01/2024-06/04/2025), UPMC (baseline: 1/1/2022-04/30/2024 and follow-up: 05/01/2024-06/04/2025), RCCA (baseline: 1/1/2022-01/01/2024 and follow-up: 02/01/2024-06/04/2025). For the baseline period, we completed a retrospective analysis of the antiemetic utilization within the practices’ HER2+ and HER2-low patient cohorts. The results of the initial baseline analysis were shared with practice leaders and among oncologists at the practices. The practices updated antiemetic order-sets, and we evaluated the order-set changes during the follow-up period to account for any improvement in antiemetic utilization. Data are presented using descriptive statistics. Results: The total pts evaluated in the initiative were: HOG baseline (49 pts) and follow-up (27 pts); UPMC baseline (212 pts) and follow-up (110 pts); and RCCA baseline (132 pts) and follow-up (99 pts). In the follow-up analysis, utilization of the recommended combinations of antiemetics (5HT3+NK1+O±DEX or 5HT3+NK1±DEX) increased from 47% to 85% at RCCA, from 29% to 100% at UPMC, and from 49% to 100% at HOG, with the overall rate increasing from 37% to 94%. Conclusion: This multi-practice quality initiative led to improved antiemetic utilization that is in line with NCCN guidelines in HER2+ and HER2-low mBC pts treated with T-DXd. These findings highlight that with established guidelines, oncology practices can benefit from regularly evaluating their own data to assess their treatment compared to the latest clinical standards.

N. S. Verma¹, R. Kannaiyan², K. Lathrop²; ¹Internal Medicine, UTHSCSA, San Antonio, TX, ²Hematology and Oncology, UTHSCSA, San Antonio, TX.

Intro Calciphylaxis is commonly associated with CKD and results from calcium deposition in dermal and adipose vasculature1. Diagnosis is often challenging with lesions typically presenting on the lower extremities or abdomen; involvement of the breast is rare2. This case describes a patient with breast calciphylaxis requiring multi-specialty management. Case Presentation A 69-year-old female with a history of grade 3 ER+/PR+/HER2− right breast intraductal carcinoma, status post partial mastectomy, axillary dissection and right breast radiation, presented with progressive skin changes of the right breast. Prior systemic therapy included two cycles of cyclophosphamide and docetaxel (discontinued due to rectal bleeding requiring exploratory laparotomy and partial colectomy), hormonal therapy, and radiation. Medical history is also significant for ESRD on HD, CHF, and pulmonary hypertension. Patient was diagnosed with breast cancer in 2012 and had been under routine oncologic surveillance. In 2022, she noticed skin changes involving the right breast. Examination revealed skin thickening beneath the right breast, with satellite lesions and areas of hyperpigmentation and hypopigmentation. A biopsy of the right inframammary fold demonstrated dermal sclerosis and minute calcifications. These findings raised suspicion for radiation dermatitis versus calcium deposition. However, malignancy could not be definitively excluded, as the initial punch biopsy failed to penetrate the dense, plate-like nodules adequately. Screening mammograms remained negative since her initial diagnosis. The patient’s symptoms progressed with skin breakdown and drainage in areas of calcification. Laboratory studies remained consistent with ESRD but showed no acute uremic exacerbation. A recent breast ultrasound revealed multiple calcified areas, most prominent in the inferior breast, consistent with calcinosis cutis. The patient’s pain and tenderness became severe enough to preclude further mammography. Treatment attempts included antifungal and barrier creams, calcium binders, and a trial of sodium thiosulfate, none of which provided significant relief. The patient was not a suitable candidate for calcium channel blockers or bisphosphonates. Surgical excision was deemed high-risk due to the extensive resection area required, with concerns regarding poor wound healing, dehiscence, and recurrence. The patient declined surgical intervention and opted for continued follow-up with dermatology and the wound care. A repeat biopsy, two years after the initial one, demonstrated dermal fibrosis, perivascular plasmocytic inflammation, and vascular ectasia, without evidence of malignancy. Discussion Calciphylaxis is a rare but often fatal condition, with wound-related infections contributing to mortality rates of up to 60% within one year3. This case highlights the need for a high index of suspicion, particularly in patients with ESRD and lesions in uncommon locations such as the breast. Diagnosis can be difficult due to overlapping features with conditions like radiation dermatitis or recurrent malignancy and may require multiple biopsies. In this patient, differentials included calcinosis cutis, scleroderma, inflammatory breast cancer, and chronic radiation dermatitis. Classic calciphylaxis pathology findings include medial calcification of dermal arterioles, fibrointimal hyperplasia, microthrombi, and necrosis, demonstrating some overlap with pathology seen in this case. Although calciphylaxis is strongly associated with ESRD, most dialysis patients do not develop it. In this patient, the coexistence of malignancy, prior radiation, and ESRD may have played a synergistic role in disease development.

B. Worster¹, K. Parton²; ¹Supportive Oncology, Jefferson Health, Philadelphia, PA, ²Senior Data Modeler, EO Care, Boston, MA.

Guided cannabis care and its impact on personally important outcomes among cancer patients: a prospective assessmentBackground:Increasingly, patients with cancer explore cannabis as an adjunct therapy to help manage symptoms and improve quality of life. However, rigorous evaluations of its effectiveness in supporting meaningful functional gains—particularly those prioritized by patients themselves—remain limited. Personally Important Outcomes (PIOs) provide a patient-centered metric that targets specific daily activities each individual deems critical to their quality of life. We set out to determine whether a structured, guided cannabis care program could meaningfully improve patient-designated PIOs.Methods:Patients were recruited from multiple oncology centers, a dedicated marketing site, and various cancer advocacy organizations. Each patient completed an intake survey covering their health history, personal information, and a baseline PIO survey, identifying up to three activities they wished to track (e.g., walking, cooking). Each activity was scored on a 10-point scale, with a total of 119 activities tracked across 49 patients. Using a Bayesian model built from available research and real-world outcomes data, a personalized care plan was constructed by integrating patient profiling inputs into individualized recommendations for products, dosages, and times of use. The plan was then reviewed by a clinician before being sent to the patient. Regular check-ins were conducted to monitor efficacy and side effects, and the regimen was adjusted as needed based on patient feedback. Throughout treatment, periodic reassessments of PIO scores allowed investigators to track functional changes over time and determine whether cannabis interventions correlated with improvements.Statistical Analyses:To quantify the magnitude of changes in PIO scores, we conducted a paired-sample Cohen’s d analysis comparing baseline and an average of follow-up assessment scores.Results:Analysis of changes in PIO scores revealed a large effect size (Cohen’s d=1.01), indicating a substantial improvement in patients’ ability to engage in their activities. This effect was statistically significant (p=0.000). At baseline, participants frequently cited mobility challenges, fatigue during daily tasks, and difficulty with daily activities as key concerns. Following guided cannabis care, many reported higher levels of daily functioning and reduced perceived difficulty. At 4 weeks, only 15% of patients experienced side effects, which included dizziness, anxiety, feeling overly intoxicated, or an elevated heart rate. Qualitative feedback suggested that patients valued having a structured approach to cannabis, including guidance on product selection and dosing strategies tailored to their symptoms. Such individualized support may have enhanced treatment adherence and optimized outcomes. Conclusions:These data underscore the potential of guided cannabis care to deliver meaningful functional improvements for both survivors of cancer and for patients in active cancer treatment. Because PIOs reflect personal priorities—rather than generic benchmarks—this method captures patient-specific progress in a more nuanced manner than many existing patient-reported outcome measures. An effect size of 1.01 demonstrates that the improvement is both clinically relevant and statistically robust, reinforcing the importance of incorporating guided cannabis care into oncology care when appropriate.

H. S. Wenning¹, T. Takahashi², A. Argulian³, R. Bardhan⁴, K. Chida⁵, R. Paredes⁶, Y. Fujiwara⁷, A. M. Roy⁸; ¹Hematology-Medical Oncology, Oncology Hematology Care, Inc, Cincinnati, OH, ²Department of Medicine, University of Hawaii, John A. Burns School of Medicine, Honolulu, HI, ³Icahn School of Medicine, The Mount Sinai Hospital, New York, NY, ⁴Department of Medicine, The Jewish Hospital – Mercy Health, Cincinnati, OH, ⁵Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, ⁶Department of Medicine, Icahn School of Medicine at Mount Sinai Beth Israel, New York, NY, ⁷Hematology-Medical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, ⁸Department of Medicine, The Ohio State University, Columbus, OH.

Introduction: Antibody-drug conjugates (ADCs) have emerged as a transformative therapeutic class in breast cancer (BC), offering targeted cytotoxic delivery with improved efficacy; however, interstitial lung disease (ILD) and pneumonitis have been increasingly recognized as serious, and sometimes fatal, toxicities. Their incidence, severity, and clinical predictors remain incompletely characterized across trials. This meta-analysis quantifies and explores the potential predictors of ILD and pneumonitis in BC patients treated with ADCs. Methods: We conducted a systematic review and meta-analysis of phase I-III clinical trials evaluating ADCs in BC to estimate the pooled incidence of ILD, including drug-related pneumonitis, and to assess potential contributing factors. ILD rates were stratified by Common Terminology Criteria for Adverse Events (CTCAE) grade. The incidence was pooled using a random-effects proportional meta-analysis. Subgroup and meta-regression analyses evaluated the impact of ADC type, payload, dose, BC subtype, drug-antibody ratio (DAR), and line of therapy. Study and subgroup heterogeneity were evaluated using the I² statistic, with I² greater than or equal to 50% considered high. Results: Across the 48 included trials (N = 10607 patients), 664 developed ILD/pneumonitis, yielding a pooled incidence of ILD/pneumonitis of 7.5% (95%CI: 4.5%-11.2%; I² = 96.2%, τ² = 0.0321, p < 0.0001). Most events were low-grade (grade 1-2: 6.4%), with fewer high-grade (grade 3-4: 0.4%) and fatalities (grade 5: 0.2%) events.The ADC, ARX788 had the highest overall ILD incidence (47.6%), largely driven by grade 1-2 events (42.0%). Trastuzumab deruxtecan (T-DXd) also demonstrated notable ILD incidence at 12.5%, including a fatality rate of 0.93% (grade 5).In a mixed-effects meta-regression model, payload type significantly influenced ILD incidence (R² = 90.3%, p 0.05). ILD incidence by payload was highest with DXd (10.7%), and lower with microtubule inhibitors (3.3%). Notably, studies that excluded patients with pre-existing lung disease reported a slightly higher pooled ILD rate (10.0%).Treatment modifications due to ILD/pneumonitis (dose reduction, delay, or discontinuation) occurred most frequently with T-DXd, particularly in DESTINY-Breast(DB)03 (11.9%), DB-02 (9.4%), and DB-01 (9.2%). Across studies reporting these outcomes, discontinuation rates ranged from 0.0% to 11.9% (median: 2.8%, IQR: 0.3%-4.8%). Conclusion: ILD, including pneumonitis, is a clinically relevant toxicity of ADC therapy in BC. Incidence and severity vary across agents. Payload type emerged as the strongest predictor of ILD risk, underscoring its importance in ADC development and patient selection. ARX788 was associated with the highest ILD risks, while T-DXd had the highest rate of treatment interruptions.

A. Basta¹, A. Klug¹, G. Ni¹, L. Wajahat¹, W. Alhassani¹, M. Awad¹, V. Khatri², R. Costa³, M. Mills², I. Washington², R. Diaz², K. Ahmed²; ¹Morsani College of medicine, University of South Florida, Tampa, FL, ²Radiation Oncology, Moffitt Cancer Center, Tampa, FL, ³Breast Oncology, Moffitt Cancer Center, Tampa, FL.

Utilization and safety of concurrent antibody drug conjugates alongside extracranial radiation therapy in the real-world setting Ameer Basta, Alexander Klug, Gabris Ni, Leena Wajahat, Wid Alhassani, Mark Awad, Vaseem Khatri, Ricardo Costa, Matthew Mills, Iman Washington, Roberto Diaz, Kamran Ahmed Background Antibody-drug conjugates (ADCs) have become an integral part of systemic therapy for breast cancer. As radiation therapy (RT) continues to play a central role in the management of breast cancer, the safety of combining ADCs with RT has become an emerging area of clinical interest. However, there remains limited data regarding the safety of ADCs administered concurrently with extracranial RT. This study aims to assess real-world data on the safety of combining ADCs with extracranial RT. Method A retrospective chart review of patients who received concurrent ADC therapy (trastuzumab emtansine (T-DM1), sacituzumab govitecan (SG), and trastuzumab deruxtecan (T-DXd)) and extracranial RT at a single academic institution was conducted. RT was delivered to the breast and/or chest wall with or without regional nodal irradiation (RNI). Demographic, clinical, and treatment data as well as adverse events were extracted from the electronic medical record. Concurrent therapy was defined as ADC administration within 4 weeks before or after the start of RT. Results A total of 49 patients who received extracranial RT in conjunction with ADCs were included in this retrospective analysis. Average months of follow up for the patients was 22 months after receiving RT. The median age of patients was 54 (range 30-76) at the time of RT. A majority patients were stage 0-2 (n=32, 65%), HR+ (n=35, 71%), HER2+ (n=40, 82%), post-menopausal (n=31, 63%), and received T-DM1 (n=43, 88%). Four patients received SG and two patients received T-DXd. The most common site treated was the chest wall with regional nodal irradiation (n=26, 53%) with 50 Gy in 25 fractions (n=34, 69%). The most frequently reported side effects were grade 1-2 skin dermatitis which was reported in 36 patients (73%), and fatigue in 22 patients (45%). Three patients had grade 3 dermatitis and one had grade 1 esophagitis. Importantly, no radiation courses were discontinued due to adverse effects. Conclusion In our study of concurrent use of ADCs with RT to breast and/or chest wall +/- RNI, no unexpected toxicities occurred. This study adds to real-world evidence that extracranial radiation therapy can be safely administered alongside ADCs.

C. M. Emeasoba¹, C. okoye²; ¹Internal medicine, UAM, fayettville, AR, ²Internal medicine, North east Georgia, Gainesville. GA, AR.

Background: Clonal hematopoiesis of indeterminate potential (CHIP), defined by somatic mutations in hematopoietic stem or progenitor cells without cytopenias, dysplasia, or overt hematologic malignancy, is a common age-related phenomenon. Its prevalence increases with age, affecting 10-20% of individuals over age 70 and up to 40% of older women with breast cancer. CHIP is enriched in patients exposed to cytotoxic therapies—particularly anthracyclines and alkylating agents—which may drive the selection and expansion of clones harboring high-risk mutations, notably in TP53 and PPM1D, genes involved in the DNA damage response. While initially described in hematologic contexts, CHIP has emerged as a potent risk factor for cardiovascular disease (CVD), including coronary artery disease, myocardial infarction (MI), and heart failure (HF). Independent of traditional cardiovascular risk factors like hypertension, diabetes, and hyperlipidemia, CHIP confers a two- to four-fold increase in CVD risk. Despite these associations, CHIP remains unaccounted for in current cardio-oncology guidelines from the American Heart Association (AHA) and American College of Cardiology (ACC). Methods: We conducted a comprehensive literature review using PubMed, Scopus, and Embase through June 2025. Peer-reviewed studies were included if they assessed CHIP prevalence, gene mutation profiles, CVD outcomes, or anthracycline-induced cardiotoxicity (AIC) in breast cancer patients. Key data extracted included mutation frequencies, clonal evolution post-chemotherapy, hazard ratios (HRs) for cardiovascular events, and left ventricular ejection fraction (LVEF) changes. Results: CHIP mutations—particularly in DNMT3A, TET2, ASXL1, TP53, and PPM1D—are found in 15-40% of breast cancer patients, often detectable prior to chemotherapy. TP53 and PPM1D mutations frequently expand post-anthracycline exposure. Population studies report a 25-100% increase in risk for HF and MI in individuals with CHIP, with TET2 and ASXL1 mutations showing the strongest associations. Mechanistically, CHIP promotes chronic inflammation via IL-1β and NLRP3 inflammasome activation, leading to myocardial injury and fibrotic remodeling. One prospective cohort study found CHIP to be independently associated with an eight-fold increased risk of symptomatic HF or LVEF decline after anthracycline therapy, even after adjusting for age, cumulative dose, and baseline risk factors. However, data remain limited by small sample sizes, heterogeneous cancer types, and inconsistent CHIP definitions. Conclusion: CHIP is a common, age-related genomic alteration with significant cardiovascular implications in breast cancer patients, especially those treated with anthracyclines. Despite emerging evidence linking CHIP to AIC, it remains absent from current risk stratification models. Prospective, breast cancer-specific studies are needed to validate CHIP as a predictive biomarker and inform its integration into personalized cardio-oncology management strategies.

M. E. Cazzaniga¹, S. Capici², G. Passarella³, F. F. Pepe², T. Clementi¹, F. Cicchiello³, F. Riva³, P. Cafaro⁴; ¹Medicine and Surgery, University of Milano Bicocca, Monza, ITALY, ²Phase 1 Research Centre, Fondazione IRCCS San Gerardo, Monza, ITALY, ³Oncology Unit, Fondazione IRCCS San Gerardo, Monza, ITALY, ⁴Oncology Unit, Fondaizone IRCCS San Gerardo, Monza, ITALY.

Background:Nausea and vomiting (NV) are the most frequent side effects in patients with metastatic breast cancer (MBC) treated with trastuzumab deruxtecan (T-DXd). Since MBC patients may receive T-DXd for an extended period, effective management of NV could help maintain dose intensity, reduce the risk of treatment discontinuation, and improve quality-of-life.Preventing NV can also contribute to reduce other adverse events, like fatigue Effective NV control from the first cycle with a NK1 receptor antagonist (RA)-based regimen is crucial for optimal management throughout subsequent cycles.This exploratory retrospective analysis examined the probability of patients experiencing NV over multiple cycles of T-DXd following antiemetic prophylaxis with NEPA, a fixed-combination of an NK1 RA (netupitant/fosnetupitant) and 5-HT3 RA (palonosetron).Methods:Occurrence and severity of NV in patients with HER2-positive or HER2-low MBC over the first 5 cycles of T-DXd for each patient were extracted and analyzed from clinical records at a single-center in Italy.Probability of NV occurring in each of 5 cycles of T-DXd was estimated using a logistic regression with NV as a dependent variable, cycle as an independent variable and with Generalized Estimating Equation to account for repeated measures. Results:Twenty-five patients were included for a total of 118 cycles. NEPA with dexamethasone was administered as prophylaxis in all but 6 cycles. The median age at T-DXd initiation was 64 years (range, 41-78). The estimated probability of developing NV was low and diminished over each cycle (Table), suggesting that NV was well-controlled with NEPA from the first cycle onward. Table: Probability of NV Occurrence During Each Cycle (Estimates Obtained from a Logistic Regression) Conclusion:These exploratory findings indicate that NEPA is likely to be highly effective in preventing NV over multiple cycles in MBC patients receiving T-DXd. It also underscores the value of using an appropriate upfront antiemetic regimen from the first cycle of T-DXd.

Z. Bielčiková¹, M. Pieniążek², A. Polakiewicz-Gilowska³, J. Żubrowska⁴, M. Holánek⁵, R. Soumarová⁶, H. Študentová⁷, A. Konieczna⁸, M. Malejčíková⁹, A. Młodzińska⁸, K. Winsko-Szczęsnowicz¹⁰, M. Lisik-Habib¹¹, A. Pękala¹¹, D. Krejčí¹², J. Šustr¹³, I. Kolářová¹⁴, I. Danielewicz¹⁵, M. Szymanik-Resko¹⁵, T. Ciszewski¹⁶, L. Rusinova¹⁷, B. Czartoryska-Arłukowicz¹⁰, A. Łacko¹⁸, R. Pacholczak-Madej¹⁹, M. Jarzab³, M. Püsküllüoğlu²⁰, M. Kubeczko³; ¹Department of Oncology, First Faculty of Medicine, Charles University, and General University Hospital, Prague, CZECH REPUBLIC, ²Department of Oncology; Breast Unit Clinical Oncology Day Care Department, rocław Medical University; Lower Silesian Comprehensive Cancer Center, Wrocław, POLAND, ³Breast Cancer Center, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, POLAND, ⁴Department of Clinical Oncology, Holy Cross Cancer Center, Kielce, POLAND, ⁵Department of Comprehensive Cancer Care, Faculty of Medicine, Masaryk University, and Masaryk Memorial Cancer Institute, Brno, CZECH REPUBLIC, ⁶Department of Oncology, Third Faculty of Medicine, Charles University, University Hospital Kralovske Vinohrady, Prague, CZECH REPUBLIC, ⁷Department of Oncology, Faculty of Medicine and Dentistry, Palacky University and University Hospital, Olomouc, CZECH REPUBLIC, ⁸Department of Breast Cancer and Reconstructive Surgery, Maria Sklodowska-Curie National Research Institute of Oncology, Warszawa, POLAND, ⁹Oncology Clinic of LFUK, National Cancer Institute, Bratislava, SLOVAKIA, ¹⁰Department of Clinical Oncology, M. Skłodowska-Curie Bialystok Oncology Center, Białystok, POLAND, ¹¹Department of Proliferative Diseases, Nicolaus Copernicus Multidisciplinary Centre for Oncology and Traumatology, Lodz, POLAND, ¹²Breast Cancer Center, First Faculty of Medicine, Charles University in Prague; Bulovka University Hospital, Prague, CZECH REPUBLIC, ¹³Department of Oncology and Radiotherapy, Faculty of Medicine in Pilsen, Charles University; University Hospital Pilsen, Plzen, CZECH REPUBLIC, ¹⁴Department of Oncology and Radiotherapy, Faculty of Medicine in Hradec Kralove and University Hospital in Hradec Kralove, Charles University, Hradec Králové, CZECH REPUBLIC, ¹⁵Oddział Onkologii i Radioterapii, Szpitale Pomorskie sp. z o.o., Gdynia, POLAND, ¹⁶Department of Metabolic Diseases and Immuno-oncology, Medical University of Lublin, Lublin, POLAND, ¹⁷Department of Oncology, Stefan Kukura Hospital Michalovce, Michalovce, SLOVAKIA, ¹⁸Department of Oncology; Breast Unit Clinical Oncology Day Care Department, Wrocław Medical University; Lower Silesian Comprehensive Cancer Center, Wrocław, POLAND, ¹⁹Department of Gynecological Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, POLAND, ²⁰Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, POLAND.

Background. Sacituzumab govitecan (SG) has emerged as a key agent in the treatment of metastatic triple-negative breast cancer (mTNBC), with use increasingly shifting toward earlier treatment lines. Consequently, the number of patients exposed to SG will continue to grow. Although recent updates to the SG summary of product characteristics list granulocyte colony-stimulating factor (G-CSF) primary prophylaxis as an option, the need for its routine use in all patients remains uncertain. We aimed to evaluate the impact of G-CSF primary prophylaxis on clinical outcomes and treatment-related toxicities in a multinational real-world cohort of patients with mTNBC treated with SG. Methods. Baseline characteristics were balanced with respect to prior systemic treatment for early-stage disease, the number of previous treatment lines in the metastatic setting, comorbidities, metastatic sites, and prior episodes of febrile neutropenia. However, ECOG performance status of 0 was more frequent in the prophylaxis group (50% vs. 37.1%, p=0.034). Efficacy endpoints included progression-free survival (PFS) and overall survival (OS), analyzed using the Kaplan-Meier method. Adverse events were assessed according to CTCAE criteria. All analyses were conducted using Stata Statistical Software version 19.0. Results. G-CSF primary prophylaxis was not associated with improved clinical outcomes. Median PFS was 4.2 months in the primary prophylaxis group versus 5.1 months in the no-primary prophylaxis group (p=0.20), with 6-month PFS rates of 38.5% vs. 42.1%, respectively. Median OS was 10.9 vs. 11.6 months (p=0.95), and 12-month OS rates were 44.9% vs. 47.1%, respectively. There were no statistically significant differences in the rates of all-grade toxicities between groups. Grade ≥3 neutropenia occurred less frequently in patients receiving G-CSF primary prophylaxis (33.0% vs. 50.7%, p=0.005), but this was not accompanied by a reduction in febrile neutropenia rates (4.0% vs. 4.4%, p=1.00). Rates of other all grade adverse events—including anemia, diarrhea, nausea, vomiting, and alopecia—were similar between groups. Dose reductions due to toxicity occurred in 36.0% of the prophylaxis group and 38.4% of the non-prophylaxis group (p=0.71). Among those who did not receive G-CSF primary prophylaxis, 74.4% eventually required secondary G-CSF support. Ultimately, only 17.2% of patients were treated with SG without any G-CSF support. Notably, SG dose reductions due to toxicity were not associated with inferior outcomes. In contrast, patients who required dose reduction had significantly longer PFS (median 6.6 vs. 3.3 months, p<0.001) and numerically longer OS (median 13.0 vs. 10.7 months, p=0.12) compared to those without dose modification. Conclusions. In this large real-world cohort, primary G-CSF prophylaxis was not associated with improved survival or reduced febrile neutropenia, though it significantly reduced the incidence of grade ≥3 neutropenia. Given that the majority of patients ultimately received G-CSF as secondary prophylaxis, and considering the relatively short treatment duration in later lines, primary G-CSF prophylaxis remains a valid option in this setting. Consistent with prior reports, SG dose reductions due to adverse events were not associated with worse survival.

C. Valenza¹, S. M. Rosenberg², K. Crowell³, K. L. Schreiber⁴, I. Bedrosian⁵, K. S. Hughes⁶, T. Lynch³, D. Basila⁷, D. Collyar⁸, E. S. Frank⁹, S. Darai¹, C. Lanahan⁶, J. R. Marks³, J. K. Plichta³, A. M. Thompson¹⁰, T. Hyslop¹¹, S. Hwang¹², A. H. Partridge¹; ¹Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, ²Department of Medical Oncology, Weill Cornell Medicine, New York, NY, ³Department of Medical Oncology, Duke University, Durham, NC, ⁴Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women’s Hospital, Boston, MA, ⁵Department of Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, ⁶Department of Surgery, Massachusetts General Hospital, Boston, MA, ⁷., Patient Leadership Team, Boston, MA, ⁸., Patient Advocates in Research, Danville, CA, ⁹., Patient Leadership Team, ., MA, ¹⁰Department of Medical Oncology, Baylor College of Medicine, Houston, TX, ¹¹Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University, Philadelphia, PA, ¹²Department of Surgery, Duke University, Durham, NC.

Background: The COMET trial demonstrated that active monitoring (AM) is not inferior to guideline concordant care (GCC) in patients with low-risk ductal carcinoma in situ (DCIS), with comparable rates of ipsilateral invasive breast cancer (iBC) and quality of life outcomes. Similarly, patients with atypical breast lesions have an increased risk of iBC and are managed with an AM strategy which could serve as a proxy for future omission of surgery in low-risk DCIS. Acknowledging that acceptance of treatment deintensification is likely linked to patient preferences, understanding, and risk perception, this analysis assessed these patient-reported outcomes (PROs) among patients with atypical breast lesions and DCIS. Methods: In this secondary analysis of the Patient-reported Outcomes after Routine Treatment of Atypical Lesions (PORTAL) Study – a multicenter cross-sectional survey study – we compared PROs from women with DCIS who received GCC, to women with high-risk breast lesions (e.g., atypical ductal hyperplasia [ADH], lobular intraepithelial neoplasia [LIN]) who underwent AM. We report on participants’ fear of invasive breast cancer (using Quality of Life in Adult Cancer Survivors [QLACS]), and disease understanding and decision quality (using Breast Cancer Surgery Decision Quality Instrument-Sections 1 and 3 [BCS-DQI-S1/3], SURE scale, Decision Regret Scale [DRS]; and Control Preferences Scale [CPS]). Descriptive statistics were provided, with means and standard deviations (SD), or proportions and 95% confidence intervals (CI). Results: 903 patients were included: 538 underwent GCC for DCIS; 365 underwent AM for ADH/LIN (Table). The mean QLACS score was 1.9/4 in both groups, indicating low to moderate fear of developing iBC, with minimal impact on quality of life. The mean knowledge of the natural history of breast lesions was 77% of patients in the DCIS group and 67% in the ADH/LIN group. In the DCIS group, 84% of patients received treatment aligned with their personal goals (concordance score, BCS-DQI-S1). Mean Decision Process Scores (BCS-DQI-S3) were 77% and 63%, respectively, indicating a high level of shared decision-making. According to the CPS, 61% of patients reported a collaborative role in decision-making. On average, there was low or no regret about treatment decision (DRSs were 12/100 and 10/100). Among patients with DCIS, 81% reported no decisional conflict (SURE scale). Conclusions: These findings suggest that women with ADH/LIN and DCIS report high levels of knowledge, goal-concordant care, and involvement in shared decision-making, potentially suggesting that AM is acceptable and presents a future opportunity to de-intensify treatment for low-risk DCIS, pending results of clinical trials.

R. Jagsi¹, A. Furgal², S. Pottow³, S. Hawley⁴, L. Wallner⁴; ¹Radiation Oncology, Emory University School of Medicine, Atlanta, GA, ²Biostatistics, University of Michigan, Ann Arbor, MI, ³Psychology, University of Michigan, Ann Arbor, MI, ⁴Medicine, University of Michigan, Ann Arbor, MI.

Background/Purpose: Worry influences treatment decision-making, surveillance behaviors, and quality of life of people with cancer. The long-term experience of worry among patients with early-stage breast cancer requires better understanding and validated instruments for efficient measurement. Methods: ICanCare enrolled 2502 women with early-stage breast cancer, diagnosed in 2013-15 and reported to Georgia and Los Angeles SEER registries, who responded to surveys in the year of diagnosis (T1). After excluding those deceased, too ill, or otherwise unable to participate, 2361 were sent follow-up surveys in 2021-22 (T2), of whom 1412 responded. We asked at both times, “During the past month, how often has worrying about your cancer coming back”: 1) “made you feel upset”; 2) “made it difficult for you to carry out your usual daily activities at home or at work”; 3) “made you feel distant from family and friends.” Response options were “almost never,” “rarely,” “sometimes,” “often,” or “almost always.” A scaled measure across the 3 items was developed using factor analysis and evaluated for internal consistency and validity in bivariate analyses with tumor and patient characteristics, using Wilcoxon/Kruskal-Wallis tests for all variables (categorical) except age (continuous), which was compared using Spearman’s correlation. The 3-item scale was also compared using Spearman’s correlation to a single item asking, “In the past month, how often have you worried about your breast cancer coming back?” Results: Table 1 shows responses among the 1165 without recurrence or second cancer at T2. Over 1 in 5 respondents (27.6% at T1 and 21.1% at T2) endorsed that worry about their cancer coming back made them feel upset at least sometimes. Factor analysis retained a one-factor solution. Cronbach’s alpha for the scale was 0.87 at T1 & 0.82 at T2. Scaled scores had mean (SD) of 1.64 (.83) at T1 and 1.43 (.67) at T2; median (IQR) 1.33 (1.00-2.00) at T1 and 1.00 (1.00-1.67) at T2. Scaled scores were higher among patients with higher stage (p=.009 at T1 and .007 at T2) and those who were younger (p<0.001 at T1 and T2), Asian and Latina (p<.0001 at T1 and T2), with lower education (p=.003 at T1, p<0.0001 at T2), divorced/separated or never married (p=.0007 at T2 only), and with lowest income (p=.002 at T2 only). At T1, the mean score on the single item was 2.16 (SD 1.13), with 37.8% worrying sometimes or more; at T2, the mean was 2.1 (SD 1.08), and 38.3% worried sometimes or more. The 3-item scale correlated with the single item (correlation coefficients T1: .71, p<.001; T2: .67, p<.001). Conclusions: Three-item and single-item measures of worry appear valid for assessing patients with early-stage breast cancer, suggesting that >1 in 5 patients has worries that extend well beyond 5 years after diagnosis. Recognizing patient and tumor characteristics associated with long-term worry may help target resources and supportive interventions.

Y. Sampathkumar¹, E. Kasuga², S. Patil³, J. Suarez², C. Lopez², Y. De Los Santos², B. Narang², P. Enriquez⁴, D. F. Makower⁵, W. G. Lichtenthal⁶, P. A. Parker⁷, T. Bao⁸, S. Rosenberg⁹, F. M. Gany², V. S. Blinder¹⁰; ¹Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, ²Immigrant Health & Cancer Disparities Service, Memorial Sloan Kettering Cancer Center, New York, NY, ³Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, ⁴School of Medicine, City University of New York, New York, NY, ⁵Medical Oncology, Montefiore Einstein Comprehensive Cancer Center, Bronx, NY, ⁶Public Health Sciences, Sylvester Comprehensive Cancer Center, Miami, FL, ⁷Counseling Center, Memorial Sloan Kettering Cancer Center, New York, NY, ⁸Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, ⁹Epidemiology, Weill Cornell Medicine, New York, NY, ¹⁰Breast Medicine Service, Memorial Sloan Kettering Cancer Center, New York, NY.

Background: Minimizing employment disruption during cancer treatment improves long-term job retention and may reduce financial hardship and its consequences, including treatment nonadherence, disease progression, and death. Patients who report receiving work accommodations (e.g., a flexible schedule) are more likely to remain employed during and after treatment. Our prior qualitative work showed that many cancer survivors were unaware of available accommodations and uncomfortable initiating requests. Symptom control during (neo)adjuvant therapy was also a barrier to continuing to work. To address these needs, we developed Talking to Employers and Medical Staff about Work (TEAMWork), a patient-informed intervention that provides education on work accommodations based on vocational rehabilitation principles, employer negotiation strategies, symptom self-management, and guidance on communicating with clinicians to enhance support (e.g., obtain work documentation). TEAMWork equips patients with strategies to effectively engage with employers and clinicians, thereby enhancing access to work accommodations and better symptom management during treatment. Methods: TEAMWork is available in English and Spanish, as a booklet and a mobile application (app). We have an ongoing randomized controlled trial comparing the TEAMWork app to the booklet. Here we present data regarding self-reported accommodations requested by study participants while enrolled on the trial. Eligible participants were women aged 18-65 years with stage I-III breast cancer who spoke English and/or Spanish, were employed pre-diagnosis, and planning to undergo systemic adjuvant chemotherapy. Patients were recruited between October 2021 – March 2025 from multiple New York City sites. Demographic and clinical data was collected through self-report and medical chart abstraction. Self-reported data on work accommodations was obtained at baseline and the midpoint of chemotherapy (mid-treatment). Results: Of the 420 participants at baseline, 89% spoke English and 11% spoke Spanish; 52.4% identified as White, 18.1% Black, and 18.1% Hispanic/Latino. The mean age was 48 years (standard deviation 9.2); 65.2% were college educated. All were employed, but only 78.5% were working at baseline. The baseline survey was completed prior to chemotherapy initiation for 47.9% of participants. Three hundred participants completed a mid-treatment survey. From baseline to mid-treatment, we observed an increased percentage of participants in both arms who reported new requests for the following accommodations: work from home (booklet: 30.1% to 41.3%; app: 28.4% to 34.4%), reduced hours (booklet: 33% to 53.8%; app: 28.4% to 45.9%), changes responsibilities or tasks (booklet: 7.7% to 29.4%; app: 10.4% to 22.9%), modified work environment (booklet: 6.2% to 18.2%; app: 8.5% to 12.1%), and additional breaks (booklet: 11% to 29.4%; app:11.8% to 22.9%). We observed a decline in new requests from baseline to mid-treatment for time off (overall: 50.7% to 45.3%) and time off to go to doctor’s appointments (overall: 76% to 60%). Conclusions: The TEAMWork intervention had promising early results in empowering patients with breast cancer to request work accommodations during chemotherapy. Declines in new requests for time off may reflect early awareness or consistent need for this type of accommodation from diagnosis through treatment, in contrast to growing needs for other accommodations throughout the treatment course. Both intervention formats, app and booklet, supported increased patient engagement in requesting accommodations, such as reduced hours and flexible work environments, which can help job retention during treatment. Future research will focus on identifying which intervention formats are most effective for different types of patients.

M. Braun¹, G. Goldzweig², I. Hasson-Ohayon³, N. Gafni², S. Paluch Shimon¹; ¹Oncology of Breast, Hadassah Medical Center, Jerusalem, ISRAEL, ²Behavioral Sciences, The Academic College of Tel Aviv Yaffo, Yaffo, ISRAEL, ³Psychology, Bar Ilan University, Ramat Gan, ISRAEL.

Objective: This study examined how Jewish and Arab women in Israel, with varying levels of religiosity, cope with metastatic breast cancer, specifically investigating the relationships between loneliness, depression, anxiety, and quality of life, and exploring the moderating roles of religiosity and spirituality. Methods: A mixed-method approach was employed, including a quantitative longitudinal component and a qualitative component consisting of in-depth interviews with a subset of the participants. The quantitative analysis involved 100 women who completed validated scales assessing loneliness (UCLA), religiosity and spirituality (SBI, FACIT-Sp), depression (PROMIS-D-SF), anxiety (PROMIS-A-SF), and quality of life (FACT-B). Results: Loneliness correlated positively with depression (r = 0.63, p < .01), anxiety (r = 0.50, p < .01), and negatively with quality of life (r = -0.55, p < .01). Cluster analysis identified four groups: (1) low loneliness-low religiosity, (2) high loneliness-low religiosity, (3) low loneliness-high religiosity, and (4) high loneliness-high religiosity, demonstrating significant differences in depression (F(3) = 18.96, p < .001), anxiety (F(3) = 10.61, p < .001), and quality of life (F(3) = 10.81, p < .001). Post-hoc analyses indicated lower depression levels in the highly lonely but highly religious group (cluster 4) compared to the highly lonely and less religious group (cluster 2). Qualitative interviews with Arab and ultra-Orthodox Jewish women highlighted belief in God as a critical resource alleviating distress and loneliness. Conclusions: High loneliness increases depression and anxiety and reduces quality of life among women with metastatic breast cancer. Religiosity and spirituality mitigate depression specifically under conditions of high loneliness. These quantitative findings, enriched by qualitative insights, underscore the importance of integrating religious and spiritual resources into psychosocial oncology care, particularly in culturally and religiously diverse populations.

H. Kolberg¹, E. Düster¹, L. Akpolat-Basci¹, H. Hoffmann², I. Swienty¹, K. Freienstein¹, C. Kolberg-Liedtke³; ¹OB/GYN, Marienhospital Bottrop, Bottrop, GERMANY, ²OB/GYN, Universitätsklinikum Essen, Essen, GERMANY, ³Applied Health Sciences, Hochschule Bochum, Bochum, GERMANY.

Introduction: Standard of care for the diagnosis of malign and benign breast tumors is a minimally invasive biopsy in cases of imaging classified BIRADS IVa and higher. This biopsy can be performed as a core cut biopsy or vacuum assisted biopsy and may be guided by sonography, mammography or MRI. The majority of biopsies are core cut biopsies guided by sonography. Whereas in cases of malign results patients in certified breast cancer centers are counseled by psychooncologists, patients with benign results are often informed in phone calls and without focus on their fears and psychological well-being. In this analysis we present data regarding the impact of breast biopsies with a benign result on patients‘ quality of life. Methods: Patients who had a core cut biopsy guided by ultrasound with a benign histological result between January 2021 and December 2023 were identified in our database. All patients received a written invitation to take part in the analysis, a questionnaire and an informed consent form. Patients who returned the questionnaire and the informed consent form were included in this analysis. The instrument we used for measuring quality of life is the short form health survey SF-36v2® (QualityMetric Inc., Johnston, USA) that contains 36 items used to measure eight domains of health-related quality of life. These parameters are compared with normative data from the QualityMetric 2009 General Population Sample. Results: 241 patients were identified who had undergone a core cut biopsy with a benign result between 2021 and 2023, 70 patients agreed to participate, submitted the questionnaire and were included in this analysis. In all eight domains of health related quality of life the results of the study population were in the category ,,same or better“ compared with the general population: physical functioning 84%, role limitations due to physical health 76%, bodily pain 73%, general health perceptions 74%, vitality 71%, social functioning 67%, role limitations due to emotional problems 67% and mental health 61%. Conclusion: We conducted a hypothesis generating analysis regarding the impact of a breast biopsy with a benign result on quality of life. We observed that all eight investigated domains of health-related quality of life were comparable or better than in the general population. Although this result may need validation in a prospective analysis it seems very improbable that the breast biopsy itself has a negative impact on quality of life. This result could help to increase the acceptance and reduce fears regarding the conduct of breast biopsy if indicated.

M. Braun¹, G. Goldzweig², O. Saar Sheffi¹, S. Klein², S. Paluch Shimon¹; ¹Oncology of Breast, Hadassah Medical Center, Nes Harim, ISRAEL, ²Behavioral Sciences, The Academic College of Tel Aviv Yaffo, Yaffo, ISRAEL.

Purpose: Young breast cancer survivors often face abrupt and premature menopause due to oncological treatments, resulting in sudden physical and psychological changes that profoundly affect their quality of life. This study aimed to examine the impact of treatment-induced menopausal symptoms on two critical domains: body image and sexual functioning, highlighting the mediating roles of menopausal symptoms and reproductive concerns, and exploring age as a potential moderator. Methods: Two complementary cross-sectional studies were conducted. In the first, 121 hormone receptor-positive breast cancer survivors and 114 healthy women completed validated measures: the Body Image Scale (BIS), Menopausal Rating Scale (MRS), and Reproductive Concerns Scale (RCS). In the second, 97 young breast cancer survivors and 75 healthy women completed the MRS and Fallowfield’s Sexual Activity Questionnaire (FSAQ). All cancer survivors also provided detailed medical history. Moderated mediation and structural equation modeling were used to examine direct and indirect pathways linking cancer survivorship, menopausal symptoms, body image, reproductive concerns, and sexual activity frequency. Results: Survivors reported significantly higher levels of negative body image, reproductive concerns, menopausal symptoms, reduced sexual pleasure, and lower frequency of sexual activity compared to controls. Menopausal symptoms and reproductive concerns mediated the relationship between survivorship and negative body image, with age moderating these pathways — indirect effects were stronger among younger women. In parallel, structural equation modeling indicated that the link between survivorship and reduced sexual frequency was explained by menopausal symptoms and diminished sexual pleasure. Somatic and urogenital menopausal symptoms emerged as key contributors to both outcomes. Conclusions: Treatment-induced early menopause plays a pivotal role in shaping young breast cancer survivors’ body image and sexual functioning. Findings underscore the importance of age-sensitive, tailored supportive care addressing both the physical side effects and the psychological and intimate dimensions of survivorship. Targeted interventions should aim to mitigate menopausal symptoms, support reproductive concerns, and enhance sexual well-being, ultimately promoting higher quality of life among this vulnerable group.

V. Bjelic-Radisic¹, K. Pogoda², D. Cameron³, G. Velikova⁴, M. Beauvois⁵, C. Coens⁵, L. Lim⁵, T. Verbiest⁵, G. Sarlet⁵, N. Nevries¹, S. Serpentini⁶, H. Abdel-Razeq⁷, J. Kaźmierska⁸, T. Kuhnt⁹, E. Fernández Lizarbe¹⁰, E. Cretella¹¹, I. Meattini¹², F. van Duijnhoven¹³, I. Rubio¹⁴, R. Popescu¹⁵, S. Hartup¹⁶, H. Roelstraete¹⁷, F. Cardoso¹⁸; ¹Senology, Helios University Hospital, Wuppertal, GERMANY, ²Department of Breast Cancer and Reconstructive Surgery, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, POLAND, ³Cancer Research Centre, University of Edinburgh, Edinburgh, UNITED KINGDOM, ⁴Institute of Medical Research, Leeds Cancer Centre, St. James’s, University of Leeds, Leeds (West Yorkshire), UNITED KINGDOM, ⁵Quality of Life Department, EORTC Headquarters, Brussels, BELGIUM, ⁶Psychoncology Unit/Breast Unit, Veneto Institute of Oncology IOV-IRCCS, Padua, ITALY, ⁷King Hussein Cancer Centre, School of Medicine, The University of Jordan, Amman, JORDAN, ⁸Electroradiology Department, Greater Poland Cancer Centre, Poznan, Poland, University of Medical Sciences, Poznan, Poznan, POLAND, ⁹Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Leipzig, Leipzig, GERMANY, ¹⁰Radiation Oncology, Hospital Universitario Ramón y Cajal, Madrid, SPAIN, ¹¹Oncology, Ospedale Generale di Bolzano, Bolzano, ITALY, ¹²Department of Experimental and Clinical Biomedical Sciences “M. Serio”, University of Florence, Firenze, ITALY, ¹³Division of Surgical Oncology, The Netherlands Cancer Institute (NKI), Amsterdam, Amsterdam, NETHERLANDS, ¹⁴Breast Surgical Oncology, Clinica Universidad de Navarra, Madrid, SPAIN, ¹⁵Medical Oncology, Tumor Zentrum Aargau and Hirslanden Klinik, Aarau, SWITZERLAND, ¹⁶St. James University Hospitals, Leeds, UK, St. James University Hospitals, Leeds, UK, Leeds, UNITED KINGDOM, ¹⁷Medical Oncology, Onze-Lieve-Vrouwziekenhuis (OLVZ), Aalst, BELGIUM, ¹⁸Advanced Breast Cancer (ABC) Global Alliance, Advanced Breast Cancer (ABC) Global Alliance, Lisbon, PORTUGAL.

Background: Breast cancer (BC) is the most common cancer among women globally. However, evidence-based follow-up strategies that address long-term risks, patient needs, and quality of life (QoL) remain limited. This study investigates the prevalence and nature of physical, psychological, and social challenges faced by women after treatment for early (EBC) or locally advanced breast cancer (LABC). Initial findings presented at SABCS 2024 showed that EBC and LABC survivors reported better overall health/QoL than the general population, but worse outcomes in insomnia, cognitive, and social functioning (as assessed by EORTC QLQ-C30)—particularly among LABC patients. This abstract focuses on results from the breast cancer-specific (EORTC QLQ-BR42) and sexual health (EORTC QLQ-SHQ-22) modules, exploring patterns by demographic and clinical variables. Methods:EORTC 1617-QLG-BCG-ROG is an international, cross-sectional, non-interventional study involving disease-free patients 1–3 years post-primary treatment (excluding endocrine therapy) for EBC or LABC. Data on institutional, demographic and clinical characteristics were collected. Patients completed the EORTC QLQ-C30, QLQ-BR42, QLQ-SHQ-22, QLQ-OUT-PATSAT-7, a follow-up strategy question, and the Distress Thermometer. A sample size of 830 was required to detect a 10-point difference between cohorts with 90% power. Stratification by age, Nottingham Prognostic Index (NPI), and treatment ensured balanced accrual. Multivariable prognostic models were constructed for each PRO scale, adjusted for propensity with a relevant relationship defined by 5% significance level. Results:From November 2020 to September 2022, 833 patients ( 82 % EBC; 17% LABC) were enrolled at 25 centres in 10 countries. A total of 805 (97%) eligible patients either fully or partially completed their questionnaires. Regarding clinical and sociodemographic characteristics, better WHO status correlates with better hand/foot symptoms/polyneuropathy, greater sexual satisfaction and perceived importance of sexual activity. Older patients reported fewer endocrine, arm, and breast symptoms, better body image and future perspective compared to younger women, as well as fewer problems with decreased libido, fatigue, treatment-related sexual issues, partnership, body image, and pain. Older patients also reported lower sexual satisfaction and worse communication with professionals, despite attaching less importance on sexual activity. Younger women, women with higher education level and those living with partner reported better sexual functioning and greater importance of sexual activity. Women with longer follow up reported more systemic, endocrine, arm, hand/foot symptoms, more weight gain and more problems with incontinence, treatment-related sexual issues, and higher sexual satisfaction. High volume institutions were associated with fewer breast symptoms but worse breast satisfaction. Private setting was linked with more endocrine and arm symptoms. Patients in follow-up in breast units reported worse skeletal symptoms compared to institutions without a breast unit. Higher nodal status correlated with poorer body image, more arm symptoms, greater fatigue, and treatment-related sexual issues. Conclusions:Despite being disease-free, women with EBC and LABC continue to experience significant QoL and sexual health challenges. Younger patients are particularly vulnerable to post-treatment symptoms. Institutional factors, such as follow-up duration and center volume, influence outcomes. Sociodemographic factors like education and partnership status positively impact sexual health. These findings are essential for developing tailored, evidence-based follow-up strategies for breast cancer survivors.

S. Nagasawa, K. Matsui, M. Furukawa, E. Kanaya, M. Araki, S. Sekine, T. Fujii; Surgery and Science,Faculty of Medicine,Academic Assembly, Toyama University, Toyama, JAPAN.

Background:Chemotherapy-induced alopecia (CIA) remains one of the most distressing side effects of breast cancer treatment, especially for younger patients. Scalp cooling systems such as the PAXMAN Orbis have shown promising results in reducing the incidence and severity of CIA, particularly in regimens involving taxanes and anthracyclines. However, most existing studies focus on single regimens, and comparative evaluations across chemotherapy backbones remain limited. This study aimed to compare the efficacy of PAXMAN in two commonly used neoadjuvant/adjuvant regimens with differing first-line agents: a dose-dense anthracycline-first regimen (ddAC→ddPTX) and a taxane-based HER2-targeted regimen (trastuzumab + pertuzumab + docetaxel: HP+DTX).  Methods:We retrospectively analyzed 62 patients with early-stage breast cancer who underwent scalp cooling using the PAXMAN system during chemotherapy at our institution between January 2021 and December 2024. Of these, 37 patients received the ddAC→ddPTX regimen, and 25 received the HP+DTX regimen. Scalp cooling was administered during each chemotherapy session. Hair loss was assessed at the end of each regimen using the CTCAE v5.0 grading system. Grade 1 or lower alopecia was defined as successful hair preservation.  Results:The overall cohort had a mean age of 49 years. In the ddAC→ddPTX group, 59.5% of patients maintained Grade 1 or lower alopecia at the end of chemotherapy. In the HP+DTX group, 64% achieved Grade 1 or lower alopecia. No serious adverse events related to scalp cooling were reported. The treatment adherence and tolerance of the PAXMAN system were high in both groups.  Discussion:Our study is one of the first to directly compare the effectiveness of scalp cooling between anthracycline-first and taxane-first chemotherapy regimens. The comparable success rates of hair preservation between the ddAC→ddPTX and HP+DTX groups suggest that PAXMAN is effective across different chemotherapy backbones, including those with known high alopecic potential. These findings provide reassurance that scalp cooling can be equally beneficial regardless of the sequencing of anthracyclines or taxanes. This is especially relevant in clinical settings where regimen choice is dictated by tumor subtype, as in HER2-positive disease. To our knowledge, this is the first comparative report from Japan on this topic. The results offer valuable evidence supporting the routine use of scalp cooling in Asian populations, who may differ in hair structure and density from Western cohorts studied previously. Further prospective, larger-scale studies are warranted to validate these findings and optimize personalized scalp cooling protocols.

Z. Xu¹, Y. Lu², Y. Wu², H. Shi¹, C. Shangguan³, K. Shen¹, Q. Qu³, N. Zhang¹; ¹Department of General Surgery, Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, CHINA, ²Department of Nursing, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, CHINA, ³Department of Oncology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, CHINA.

Background: Metastatic breast cancer (MBC) survivors require long-term treatment, resulting substantial costs and financial toxicity. Thought the financial burden was observed to be associated with cancer survivors’ clinical outcome, limited evidence focused on the toxicity on mental health. Here, we aimed to determine the association between financial toxicity and mental health and its mediators among MBC survivors.Methods: Female MBC patients diagnosed in our institution during May 2023 to October 2023 were included. Financial toxicity was assessed using Comprehensive score for financial toxicity based on the patient-reported outcome measures (COST-PROM) instrument. Mental health status was profiled through Connor-Davidson Resilience Scale (CD-RISC). To further explore the modifiable psychological symptoms, the Cancer Loneliness Scale (CLS), Cancer-related Negative Social Expectations Scale (CRNSES), M. D. Anderson Symptom Inventory (MDASI) and Perceived Social Support Scale (PSSS) were adopted to characterize loneliness, social expectations, oncology symptom awareness, and social support, respectively. The association between financial toxicity and mental health status was determined using conditional linear regression, adjusted for demographic factors, disease characteristics, treatment, and socioeconomic status. Mediation analysis with structural equation modeling (SEM) was performed to explore the mediator of the association. Further, we conducted the network analysis to profile the correlation among identified mediators, including a binary variable that encoded whether survivor was of financial toxicity. A two-tailed P < 0.05 was considered as statistically significant.Results: A total of 226 MBC survivors were included, of whom the median age were 55 (interquartile range 45 to 64 years) years, and 173 (76.5%) were with financial toxicity. Financial toxicity was significantly associated with mental health after adjusted for demographic factors, disease characteristics, treatment, and socioeconomic status (coefficient, 0.197, 95% CI, 0.024 to 0.370). CLS, CRNSES, MDASI-part 2, and PSSS were identified as the mediators (indirect effect [95% CI], CLS 0.087 [0.04 to 0.134], CRNSES 0.045 [0.009 to 0.08], MDASI-part2 0.071 [0.027 to 0.115], and PSSS 0.043 [0.008 to 0.078],all P < 0.05), which corresponding to 72.7%, 37.1%, 59.2%, and 35.9% of the relative effect, respectively. The network analysis showed that “relations (MDASI-2_4)”, “social discomfort (CRNSES_1)”, and “felt empty (CLS_6)” were the mental health nodes with the top 3 largest strength (mean [SD] of bootstrapped standardized index value, 1.79 [0.69] for “relations”, 1.71 [0.85] for “social discomfort”, and 1.57 [0.99] for “felt empty”, respectively), while the “felt empty (CLS_6)” and “perceived avoidance (CRNSES_2)” were the node with largest betweenness and closeness (mean [SD] of bootstrapped standardized index value, 2.12 [3.4] for “felt empty and 1.36 [2.40] for “perceived avoidance”), respectively.Conclusion: Financial toxicity was significantly associated with worse mental health. Targeting certain dimensions regarding loneliness, social expectations, oncology symptom awareness, and social support might could reverse the toxicity.

R. C. Cangussu¹, L. Andrade¹, L. Testa², C. Lima³, A. S. Ferreira⁴, C. M. Moniz², S. R. Chagas⁵, P. M. Hoff², M. Estevez-Diz², R. Colombo Bonadio²; ¹Oncology, Instituto D’Or de Pesquisa e Ensino, Salvador, BRAZIL, ²Oncology, Instituto D’Or de Pesquisa e Ensino, São Paulo, BRAZIL, ³Oncology, Instituto D’Or de Pesquisa e Ensino, Recife, BRAZIL, ⁴Oncology, Instituto D’Or de Pesquisa e Ensino, Brasília, BRAZIL, ⁵Oncology, Instituto D’Or de Pesquisa e Ensino, Rio de Janeiro, BRAZIL.

Knowledge and Adherence to Exercise Recommendations Among Oncologic PatientsBackground: Physical activity positively influences various aspects of cancer treatment. Among patients (pts) undergoing active therapy, it improves physical capacity, treatment tolerability, and reduces side effects. For cancer survivors, it lowers the risk of recurrence of tumors such as breast and colorectal. Despite its importance, the extent to which pts are informed about exercise recommendations remains unclear.Methods: We conducted a self-administered survey to evaluate exercise habits and knowledge among cancer pts treated between 2022 and 2024. Participants were recruited from a private oncology network (with units across Brazil) and two public cancer centers. Pts, irrespective of tumor type, disease stage, or treatment phase, completed the survey via RedCap.Results: Of the 394 pts who answered the survey, 76.4% were female. Median age was 56 years (range 23 – 92). The cohort included 52.8% self-identified white pts and 44.8% black/mixed race pts; 63.9% were treated in the private health system and 36.1% in the public. The most common primary tumors were breast (47.7%) and gastrointestinal (16.2%). While 85.9% reported receiving any exercise recommendations from physicians, only 62.5% described themselves as physically active. In addition, 30.7% stated they lacked knowledge about the type or duration of recommended exercises. Exercise guidance and adherence were lower among patients treated in public health centers, black/mixed race pts, and those with non-breast cancer (Table). Notably, 94.2% of pts without sufficient information expressed a desire to learn more about exercise.Conclusion: Although a majority of cancer pts receive general recommendations on physical activity, adherence and understanding of specific exercise guidelines remain suboptimal. Variability in exercise awareness based on health system type and race highlights disparities that must be addressed. Promoting physical activity awareness and accessibility, particularly in resource-limited settings, is crucial. Exercise should not remain a privilege for a few but rather a fundamental aspect of care accessible to all pts, regardless of their circumstances. Table

M. Alharbi¹, K. Ahuja¹, Z. Shah¹, J. Mussel¹, S. Gandhi², A. AbuSanad³, V. Gupta¹, L. S. Agrawal⁴, A. M. Roy⁵; ¹Department of Medicine- Division of Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, ²Department of Medicine- Division of Oncology, Emory Winship Cancer Institute, Atlanta, NY, ³Department of Internal Medicine- Devision of Oncology, King Abdulaziz University, Jeddah, SAUDI ARABIA, ⁴Department of Medicine- Division of Oncology, Norton Cancer Institute, Louisville, KY, ⁵Department of Medicine- Division of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH.

Background Clinical guidelines recommend addressing sexual health (SH) as part of routine oncology practice, yet only 20-29% of patients with breast cancer (BC) report receiving SH counseling. SH remains mostly excluded from formal medical training. This study explored the current knowledge, attitudes, and barriers to SH counseling among oncology trainees working in breast oncology settings globally. Methods A cross-sectional study was conducted among medical oncology residents/fellows, breast and gynecology surgical fellows, and radiation oncology residents. Anonymous self-administered surveys were distributed via social media platforms, including X, LinkedIn, WhatsApp, and email. Surveys collected demographics, self-reported SH knowledge, practices, and barriers to SH counseling. Data were analyzed using descriptive statistics. Results Among 46 oncology trainees, 52% were male, and 48% female, with the majority aged 31-35 years (48%). Most were in advanced training levels (PGY4-6), and 91% were in medical oncology. Respondents were trained in the US (70%), Middle East (17%), Europe (9%), and Asia (4%). A majority (89%) reported limited knowledge of SH dysfunction during cancer treatment. Table 1 summarizes self-reported confidence in managing SH concerns. SH was infrequently assessed; 48% reported they rarely addressed it, and only 26% indicated they usually/always did. 65% indicated that SH counseling is their responsibility. Biases were common:70% were more likely to discuss SH with younger patients (<50), and 52% with those with early-stage BC. When asked to select all appropriate times to address SH, 72% chose active/post-treatment, 43% at diagnosis, 41% during survivorship, and only 15% throughout care. 46% of trainees were moderately concerned about prescribing vaginal estrogen to patients with BC on endocrine therapy; 33% had prescribed vaginal estrogen, and 37% had prescribed erectile dysfunction medication. Overall, 94% reported insufficient SH training, with around 60% receiving no training to counsel females, males, or transgender patients with BC. 81% supported individualizing SH discussions, 68% felt patients value them, 50% feared offending patients by initiating them. Awareness of institutional SH resources was low with many unsure of availability of pelvic floor therapy 50%, sex therapy 59%, and behavioral therapy 50%. Commonly reported barriers to SH counseling included lack of training 85% and time 65%, followed by cultural sensitivity, provider discomfort, and perceived lack of effective treatment. Importantly, 83% supported more SH education, with seminars 83%, shadowing SH experts 50%, online courses 50%, and simulation-based training 26%. Conclusion Oncology trainees worldwide treating BC report inadequate training in SH, low confidence, and limited awareness of available resources. Formal education and social media engagement may help bridge the counseling gap.

C. Liu¹, M. Deban¹, J. Newman-Bremang¹, R. Warburton¹, C. Dingee¹, J. Pao¹, A. Bazzarelli¹, J. Sutherland², E. McKevitt¹; ¹Department of Surgery, University of British Columbia, Vancouver, BC, CANADA, ²Centre for Health Services and Policy Research, University of British Columbia, Vancouver, BC, CANADA.

Background: Guidelines support both breast-conserving surgery (BCS) with radiation and mastectomy for treatment of early breast cancer, but emerging evidence favoring BCS challenges the practice of universally offering both options to patients. There is currently no comparative study assessing health-related quality of life outcomes (HRQoL) across BCS, medically necessary (Mast-MN), and patient preference mastectomy (Mast-PP). This study compared the preoperative and six-month postoperative change in HRQoL in aspects of mental, physical health, and satisfaction between these surgical approaches. Methods: This prospective cohort study enrolled breast cancer surgery patients between 2021 – 2024 at our provincial referral center. Participants completed surveys measuring mental and physical health preoperatively and six-months postoperatively. The BREAST-Q questionnaire was used to assess breast cancer specific outcomes including breast satisfaction, psychosocial, sexual, and chest physical well-being. General patient-reported outcomes were categorized in depression, anxiety, pain, and perceived health. Results: A total of 494 patients meeting inclusion/exclusion criteria completed both pre- and six-month postoperative surveys. Of these, 343 underwent BCS, 104 Mast-MN, and 47 Mast-PP. On average, BCS was associated with a clinically significant increase in breast satisfaction (+4.3) and physical-chest well-being (+7.5). Mast-PP showed a decline in physical-chest well-being (−5.6), while Mast-MN showed reductions in breast satisfaction (−6.2), psychosocial (−5.4), and sexual well-being (−12.2). In multivariable regression, both Mast-PP (β = −7.91, 95% CI: −15.2 to −0.63, p = 0.033) and Mast-MN (β = −12.3, 95% CI: −17.4 to −7.13, p < 0.001) were associated with significantly lower postoperative breast satisfaction compared to BCS. There was no significant difference in depression, anxiety, pain, or perceived health scores within and across the surgical modalities. Conclusions: BCS was associated with significantly greater breast satisfaction postoperatively, and trends toward improved chest physical well-being compared to both medically necessary and patient preference mastectomy. When deciding surgical approach, patients should be counseled on these quality-of-life considerations when BCS is feasible.

H. Kadar Sfarad¹, M. Feret², C. Padilla³, A. Balari⁴, J. Janin⁵, E. Avisar¹; ¹Breast Surgical oncology, University of Miami, Miami, FL, ²Radiation Oncology, University of Miami, Miami, FL, ³School of Medicine, Universidad del Norte, Colombia, COLOMBIA, ⁴Surgery, University of Miami, Miami, FL, ⁵School of Medicine, University of Miami, Miami, FL.

Background: Patients with breast cancer undergo axillary lymph node dissection under certain indications. One of the main side effects of axillary dissection is upper limb lymphedema that occurs in 15-40% 0f cases and can be debilitating. An objective measurement of lymphedema is Bioimpedance spectroscopy, that produces an LDEX Score and can detect subclinical lymphedema. There are several risk factors for developing lymphedema after axillary dissection, among them obesity, radiation therapy, wound complication and higher age. SLYMPHA is a surgical prevention of breast cancer related lymphedema, in which the breast surgeon is performing connection of lymphatic ducts from the upper limb to venous source. This method has been proven to reduce incidence of lymphedema to 10%. Our aim is to explore the effect of different radiation techniques and fields on the development of breast cancer related lymphedema in patients after axillary dissection and and SLYMPHA. Method: We established a retrospective database of all patients who underwent axillary dissection and SLYMPHA for breast cancer from 2014-2021, and collected demographic, clinical, surgical and radiation data. For each patient we observed L-dex measurement at pre-operative setting and 6,9,12,24 months post-operative setting as well as clinical examination for LE development. Binomial logistic regression was used to identify associations between clinical data, radiation methods and field, and LE incidence. Results: Among 219 patients, 136 had LDEX assessments, with 30 patients (13.6%) developing BCRL. Factors found to be related to elevated risk of LE included older age, higher BMI, recurrent cancer, reconstructive surgery and having N2/N3 nodal disease. Radiation therapy was found to be correlated with higher levels of lymphedema, especially with radiation techniques such as Three-Dimensional Conformal Radiation Therapy and Intensity Modulated Radiation Therapy/Volumetric Modulated Arc Therapy. Radiation to chest wall field and Comprehensive radiation excluding dissected axilla fields had a higher association with increased levels of LE. Conclusions: Patients undergoing axillary dissection and SLYMPHA with higher BMI, recurrent cancer, reconstructive surgery, N2/N3 disease, or adjuvant radiation treatment, as well as those receiving Intensity Modulated Radiation Therapy/Volumetric Modulated Arc Therapy or Three-Dimensional Conformal radiation techniques, have an increased risk of developing breast cancer related LE. De-escalation of radiation and better selection of radiation techniques and fields could contribute to a better lymphedema free survivorship.

W. O’connor, L. Colbert, K. Armstrong; mental health, The Boobie Queen Company, Evans, GA.

Purpose Young breast cancer survivors experience high rates of emotional distress, identity disruption, and trauma-related symptoms. One in three cancer survivors show signs of PTSD. Among breastcancer survivors, 50% report depression and 60% report anxiety post-treatment. Yet few survivorship care models address mental health in a trauma-informed or developmentally relevant way. In our 2025 survey of 46 young survivors, 93% reported distress when reminded of cancer-related events, 84% experienced intrusive thoughts, 73% had sleep disturbances, 69%reported flashbacks, and over 80% expressed discomfort with physical changes. These findings underscore the urgent need for structured, peer-informed mental health support. In response, we developed targeted mental health tools and the Phases of Cancer Survivorship (PoCS)Framework: a three-phase model (Grief, Repair, Celebration) that conceptualizes psychological healing as a progressive, survivor-centered process. Methods The PoCS Framework was developed through an iterative, survivor-informed process. From2022 to 2025, 90 young breast cancer survivors participated in semi-structured interviews and surveys following 12 immersive peer-led retreats. Thematic analysis of participant narratives was conducted by a licensed mental health counselor and a multidisciplinary team to identify common psychosocial challenges. Key themes included emotional overwhelm, fear of recurrence, identity disruption, body image distress, professional delays, loneliness, and a desire to feel “normal” again.The framework includes three nonlinear, cyclical phases reflecting the evolving emotional experience of young survivors. The Grief Phase survivors process fear, loss, and trauma through reflection and trauma-informed dialogue. The Repair Phase survivors build emotional regulation and self-compassion through psychoeducation and skill development. The Celebration Phase survivors reclaims joy and identity through rituals, empowerment, and community connection.Retreat programming integrated the framework through group therapy, psychosocial education, art therapy, and original workbook tools. Emotional impact and utility were assessed through post-retreat surveys and open-ended feedback. Results Retreat participants reported 92% increased understanding of their mental health, 90%reported improved body image, 92% felt less alone and more connected to community, and 88% felt more confident and empowered. Qualitative feedback described the framework as “validating,” “clarifying,” and “exactly what I needed but didn’t know how to ask for.” Participants highlighted symbolic and expressive activities as emotionally transformative. Emergent themes included reduced shame, increased hope, empowerment, and clearer emotional navigation. Feedback supported the framework’s resonance, relevance, and potential for broader use in trauma-informed survivorship care. Conclusion Findings highlight the urgent need for structured, developmentally relevant psychosocial support throughout survivorship. The PoCS Framework addresses critical, unmet mental health needs among young breast cancer survivors. This model offers an integrable, emotionally resonant structure that bridges gaps in care and provides a shared language for oncology and mental health providers and patients. Its alignment with survivors’ lived experiences positions it for broader use in clinical navigation programs, community-based services, and direct patient support. The PoCS Framework has the potential to become a universal language for the survivor experience, guiding emotional recovery, and enhancing quality of care across settings. Further study is warranted to validate its impact and guide implementation at scale.

D. Rodriguez¹, P. Chalela¹, Y. Lew¹, N. Rodriguez¹, J. Ramos¹, J. Cardenas¹, C. Carmona¹, E. Munoz¹, B. Choi¹, C. Wang¹, Y. Manresa², M. Hernandez Krause², D. Perdomo², A. Natori², S. Cole³, F. Penedo², A. Ramirez¹; ¹Institute for Health Promotion Research, UT Health San Antonio, San Antonio, TX, ²Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, ³Medicine, Hematology/Oncology, University of California, Los Angeles, CA.

Background: Hispanic/Latina (H/L) women in medically underrepresented regions, such as South Texas, face substantial disparities in cancer survivorship, including reduced quality of life (QOL) and inadequate supportive care access. Despite growing recognition of the role of non-medical determinants of health (NMDoH) – including financial strain, transportation barriers, and limited social support – few studies have quantitatively assessed their combined impact on survivorship outcomes among H/L breast and cervical cancer survivors. Objective: This study examined how various NMDoH factors predict QOL in breast and cervical cancer survivors participating in Avanzando Caminos, a large NCI-funded cohort study investigating social, cultural, behavioral, and medical influences on Hispanic/Latino cancer survivorship. Methods: Baseline data were analyzed from 170 H/L women who had completed treatment for breast or cervical cancer within the last decade. NMDoH were assessed by cross-referencing Avanzando Caminos data with items from the Avanzando Salud Center NMDoH Screener—an instrument developed by the Center to investigate NMDoH in STX—measuring financial hardship, transportation needs, physical activity, healthcare access, and social support. QOL was evaluated using cancer site-specific Functional Assessment of Cancer Therapy (FACT) scales: FACT-B for breast cancer and FACT-Cx for cervical cancer survivors. Multivariable linear regressions estimated associations between NMDoH factors and QOL, controlling for sociodemographic and clinical covariates. Results: Financial hardship emerged as a significant predictor of lower QOL across both cancer types (breast: β = -3.41; cervical: β = -8.65; p < 0.05). Among cervical cancer survivors, greater comorbidity burden also predicted reduced QOL (β = -4.49; p < 0.01). In breast cancer survivors, engagement in vigorous exercise was associated with higher QOL scores (β = 4.85; p < 0.05). Although similar trends were observed among cervical cancer survivors, smaller sample size limited statistical significance. Conclusions: Findings demonstrate that unmet NMDoH needs, particularly financial strain and comorbid conditions, adversely impact QOL among H/L cancer survivors. Tailored, culturally informed interventions addressing these social and economic challenges – such as patient navigation and community health worker models – are essential for improving survivorship experiences. Incorporating systematic NMDoH screening into survivorship care planning may enhance supportive service provision and optimize long-term health outcomes in this population.

J. D. Rogers¹, S. Cohen², M. Rosas², P. Welcsh¹, K. N. Owens¹, S. J. Friedman¹, R. H. Pugh Yi³; ¹Education, Facing Our Risk of Cancer Empowered (FORCE), Tampa, FL, ²Support, Facing Our Risk of Cancer Empowered (FORCE), Tampa, FL, ³President, Akeso Consulting, Vienna, VA.

Background:People with pathogenic variants (PV) associated with hereditary cancer risk face psychosocial challenges, including anxiety about risk-management, family communication, and feelings of isolation. While clinical guidelines are well-established for many genes linked to cancer risk, emotional support remains an unmet need. FORCE is a national nonprofit organization serving people affected by hereditary cancer risk. We provide virtual support meetings tailored for the hereditary cancer community. The meetings are organized by topic (e.g. mastectomy), situation (e.g. survivor, previvor, caregiver), gene (e.g. BRCA1/2, Lynch syndrome, others), and other factors. The meetings are co-led by genetics experts and trained FORCE peer volunteers. Past studies show that women with hereditary cancer risk experience significant emotional distress, and value referrals from their doctors to social support networks³. Perceptions of low social and emotional support are predictors of increased distress and poor mental health outcomes in this population. However, structured support groups, peer connections, and family-based emotional support improve coping, anxiety levels, and patient experience^1-3.Integrating emotional support into hereditary cancer care meets a critical need and can improve patient outcomes.Methods:Between February and July 2025, 1000 people attended 40 FORCE virtual support meetings for people affected by hereditary cancer risk. Feedback was collected from 185 attendees via a post-meeting survey to assess satisfaction, emotional support, and perceived value of information gained. Participants could also provide open-ended feedback.Results:Participants expressed that the meetings provided a safe, inclusive space to connect with others facing similar challenges, helped reduce feelings of isolation, and validated participant’s emotions: •62.4% felt less anxious or worried. •87.5% felt more supported or less alone. •82.3% felt more confident in their knowledge.•65.9% felt more confident about their decisions.•94% were “very satisfied” (71.2%) or “satisfied” (22.8%). •Attendees received support on various topics including genetic counseling/testing (40%), breast reconstruction (34%) and communication with healthcare providers (33%).Qualitative Themes:•Greater sense of community: “The support group is the only outlet for me to express my hopes, frustrations and fears.”•Empowerment in medical decision-making: “I am definitely going through with my mastectomy and am so happy I met new friends to help me through my journey!”• Improved representation: Specific groups (e.g., LGBTQ+, young previvors) felt especially seen when breakout sessions included people who shared their lived experiences.Discussion:The emotional burden of navigating hereditary cancer risk can be substantial. Survey responses demonstrated that FORCE’s peer-and-expert-led virtual meetings create a needed space for people with hereditary cancer risk to process complex emotions, build resilience, and make informed decisions. Organizing meetings by topic highlights the diversity of attendees and the importance of tailored support meetings.Conclusion:Virtual support meetings represent a scalable, low-cost, and high-impact intervention to address the emotional needs of people with hereditary cancer risk. The positive reception underscores the value of integrating psychosocial support alongside clinical care.References:1.https://doi.org/10.1080/10410236.2016.1250187 2.FORCE. (2024, October 21). Results from FORCE’s 2024 Survey Highlighting the Needs of People at High Risk for Breast Cancer. FORCE Blogs. 3.https://doi.org/10.3389/fpsyt.2019.00208

Z. Wang¹, C. L. Loprinzi², S. Abdi³, T. B. Strouse⁴, T. J. Smith⁵; ¹Medicine, Johns Hopkins, Baltimore, MD, ²Oncology, Mayo Clinic, Rochester, MN, ³Department of Pain Medicine, M D Anderson Cancer Center, Houston, TX, ⁴Psychiatry, UCLA, Baltimore, MD, ⁵Oncology, Johns Hopkins Sidney Kimmel Cancer Center, Baltimore, MD.

Background: Up to 68% of patients will experience CIPN. There are no FDA or ASCO recommended therapies. The pain (P), numbness (N), and tingling (T) can persist for month, years or even lifetime. Duloxetine reduces pain scores by 0.6-1.0 on the 0-10 scale but does not help N or T. Scrambler therapy (ST) is a novel form of neuromodulation that uses EKG electrodes on the dermatomes to capture the pain c-fiber receptors, and generate an action potential of “non-pain” information to replace the pain information. It appears to reset central sensitization by altering cerebral blood flow and re-establishing the balance of neuropeptides (e.g., NGF, GDNGF) in the blood (Smith et al NEJM 2023). Yet many professionals and patients are unaware of it. Methods: We reviewed all available studies. Results: Smith et al (2010, VCU) noted a 59% P reduction (5.8 to 2.4 at the end of 10 days (P<0.0001)) in 16 subjects, and 4 had 0 pain at day 10. Pachman et al (2015, Mayo) in 37 subjects showed a 53% P reduction by day 10; a 44% reduction in T; and a 37% reduction in N. In a randomized trial of 50 patients using ST versus TENS (transcutaneous electrical nerve stimulation), Loprinzi et al (2020, Mayo), in a randomized trial, showed more than twice as many ST patients reported a 50% improvement (36-56%) vs. TENS (16-28%). At 8 weeks the reductions were important: 33%P, 28%N, 41%T. In a subsequent crossover trial (Childs 2021) of the TENS patients to ST, 6 of 12 ST patients achieved a 50% reduction in P and T. Smith et al (2021 Hopkins) did a randomized sham-controlled trial with 35 patients but observed no lasting effect; in retrospect, the electrodes and electrode placement were incorrect in this trial. Abdi et al (2024, MDACC) did a Phase II trial of ST in 10 patients and found symptoms of N, T, trouble walking, and disturbed sleep had significant improvements at 6 months. Worst pain was reduced at 6 months by 3 points. Pain medication use decreased by 70% at the end of treatment and by 42% at 6 months. Patient satisfaction was high (82%) and no adverse events with ST treatment were reported. Wang Z. et al (Hopkins, unpublished data 2025) showed a 60% reduction in pain (6.2 to 2) in twelve subjects, with one achieving complete remission. Strouse et al (2025, UCLA) will soon report similar results in over 60 patients. Wang E. et al (2023, Hopkins) reviewed 1152 patients treated with ST and found just 3 adverse events: one hematoma and two red spots under the EKG electrodes. The only other therapy that reduces all the symptoms of CIPN is spinal cord stimulation (Gupta 2024) but that is invasive, expensive, and can cause a multitude of adverse events. Conclusions: Scrambler Therapy is a safe and effective treatment for the P, N, and T of CIPN with rare and minimal side effects in a syndrome with no other effective treatment. It is hindered by reimbursement ($32/30 minutes, the same as TENS even though the technology is completely different). Scrambler Therapy should become more available in the future.

N. Tamura¹, Y. Nagaoka², Y. Sano³, Y. Kobayashi¹, K. Tanaka¹, M. Kurikawa¹, A. Shibata¹, Y. Tanabe⁴, Y. Yamaguchi⁴, Y. Oda⁵, M. Ogura⁵, R. Okamoto⁶, H. Kawabata¹; ¹Department of Breast and endocrine surgery, Toranomon Hospital, Tokyo, JAPAN, ²Cancer Chemotherapy Nursing, Toranomon Hospital, Tokyo, JAPAN, ³In-hospital beauty salon、ANKS, Toranomon Hospital, Tokyo, JAPAN, ⁴Department of Medical Oncology, Toranomon Hospital, Tokyo, JAPAN, ⁵Department of Pharmacy, Toranomon Hospital, Tokyo, JAPAN, ⁶Department of Pathology Photo Gallery, Toranomon Hospital, Tokyo, JAPAN.

Background: Chemotherapy-induced alopecia (CIA) significantly impacts patients’ quality of life (QoL). While scalp cooling therapy (SCT) offers a proven method for preventing CIA, its widespread implementation faces various challenges. Objective: This study aimed to evaluate the impact of a refined team-based approach and optimized protocols on scalp cooling therapy (SCT) efficacy in breast cancer patients. Methods: A retrospective observational study compared SCT outcomes in breast cancer patients before and after implementing a refined team-based approach (Group A vs. Group B), supplemented by a concise literature review. Results: Our institutional experience demonstrated improved efficacy in preventing alopecia with enhanced team collaboration and the active involvement of appearance care professionals, including hairdressers. Importantly, chemotherapy regimen sequencing significantly influenced outcomes. In Group A, patients receiving weekly paclitaxel followed by dose-dense doxorubicin/cyclophosphamide (wPTX f/b ddAC) had a significantly shorter average number of Grade 2 or higher alopecia cycles (mean: 1.007, median: 0.5) compared to those receiving the reverse sequence (ddAC f/b wPTX, mean: 2.870, median: 3.0) (P = 0.0006). In Group B, while wPTX f/b ddAC also showed a shorter average (mean: 0.448, median: 0.0) compared to ddAC f/b wPTX (mean: 0.800, median: 0.0), this difference did not reach statistical significance (P = 0.0543), potentially reflecting the overall improved efficacy in this group. For patients receiving wPTX f/b ddAC, the percentage of Grade 2 alopecia at the end of treatment was 44.8% in Group B, significantly lower than 69.2% in Group A. The overall proportion of time spent in Grade 2 alopecia during the entire treatment period also demonstrated a shorter duration in Group B (6.5%) compared to Group A (17.3%). Furthermore, comparing the average number of cycles with Grade 2 or higher alopecia, Group B (0.448 cycles) demonstrated a significantly shorter duration compared to Group A (1.007 cycles; P=0.0055). For ddAC f/b wPTX, Group B (0.800 cycles) also showed a significantly shorter average number of cycles with Grade 2 or higher alopecia compared to Group A (2.870 cycles; P=0.0003). For TC therapy, the average number of cycles with Grade 2 or higher alopecia did not yield a statistically significant difference (Group A: 3.000 cycles; Group B: 2.550 cycles; P=0.1176). For the PEM/Cb/wPTX→PEM/AC regimen, Group B (0.000 cycles) demonstrated a significantly shorter average compared to Group A (3.000 cycles; P=0.0002).Conclusion: Maximizing SCT efficacy requires not only technical proficiency but also a comprehensive multidisciplinary team approach and personalized, high-quality care. Specifically, optimized chemotherapy regimen sequencing, alongside the active involvement of appearance care professionals like hairdressers, significantly enhances efficacy. This study highlights their crucial role in improving future SCT dissemination and quality.

S. Wang¹, S. A. Everson-Rose², A. Prizment¹, A. H. Blaes²; ¹Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, ²Medicine, University of Minnesota, Minneapolis, MN.

Background: Menopause has been associated with increased aging biomarkers, such as epigenetic clocks and inflammatory biomarkers, including interleukin-6 (IL-6) and C-reactive protein (CRP). However, no studies have examined aging and inflammatory processes in breast cancer survivors who experienced treatment-induced menopause. This study compared aging and inflammatory biomarker levels in post-menopausal breast cancer survivors with and without treatment-induced menopause. Methods: This study included 25 women who participated in the Mindfulness-Based Stress Reduction (MBSR) study, which investigated the impact of an 8-week MBSR intervention on the aging process. All participants were diagnosed with locally advanced, estrogen receptor-positive breast cancer. They had undergone surgery and were taking an aromatase inhibitor. We divided participants into two groups: Group 1 included 8 females younger than 50 years who experienced treatment-induced menopause, and Group 2 included 17 females older than 50 years who had undergone natural menopause. Blood samples were collected at baseline and at the 8-week follow up. Using the baseline samples, we measured an aging biomarker, P16^INK4a expression in T cells, which increases with age. We also measured two inflammatory biomarkers: IL-6 (pg/mL) and high-sensitivity CRP (hsCRP, mg/L). P16^INK4a expression and hsCRP levels were log2 transformed to correct for skewness. We compared the levels of P16^INK4a, IL-6, and hsCRP across groups in an unadjusted model and a model adjusted for age, chemotherapy, and radiation. Results: Participants’ characteristics for the two groups are presented in Table 1. Participants were predominantly White and highly educated. For Group 1 (treatment-induced menopause) and Group 2 (natural menopause), respectively, the mean age was 43.7 and 61.9 years, and the mean time since diagnosis was 3.8 and 4.2 years. All women in Group 1 had chemotherapy, whereas 38.9% in Group 2 had chemotherapy (p = 0.01). The prevalence of radiation was similar across groups [Table 1]. In both unadjusted and adjusted models, mean levels of P16^INK4a (Group 1 vs. Group 2 in the model adjusted for age, chemotherapy, and radiation: 5.04 vs. 5.11, p = 0.19), IL-6 (1.03 vs. 2.30, p = 0.28), and hsCRP (1.04 vs. 0.92, p = 0.92) were similar across groups. Conclusions: Despite treatment-induced menopausal breast cancer survivors being, on average, 18 years younger than those with natural menopause, both groups showed similar levels of aging and inflammatory biomarkers. These findings suggest that treatment-induced menopause may accelerate the aging process among young female breast cancer survivors. Future studies should examine whether treatment-induced menopause accelerates aging more than natural menopause and investigate longitudinal aging trajectories in treatment-induced menopausal breast cancer survivors.

I. J. Ergas¹, C. Mindemann¹, J. Roh¹, D. Lia¹, L. Raymond², V. Shim³, S. Siegel², M. Kwan¹, L. Kushi¹, R. Zwerling Baltrushes³; ¹Division of Research, Kaiser Permanente Northern California, Pleasanton, CA, ²San Francisco Medical Center, Kaiser Permanente Northern California, San Francisco, CA, ³Oakland Medical Center, Kaiser Permanente Northern California, Oakland, CA.

Background: Breast cancer has one of the highest 5-year survival rates among cancers, with over 4 million survivors in the U.S. Studies suggest that adherence to a healthy diet can reduce morbidity and mortality risk in this population. However, dietary assessment is often overlooked in routine care due to limitations of existing tools. Traditional methods such as 24-hour recalls and food frequency questionnaires are time-consuming and burdensome, particularly for patients undergoing treatment. Diet ID™ is an online, image-based dietary assessment tool that uses Diet Quality Photo Navigation—a patented visual pattern recognition algorithm. Participants compare food photos representing different dietary patterns and select the one that best reflects their typical diet over the past month. The tool generates comprehensive nutritional profiles, and a Healthy Eating Index (HEI) score. This study aims to evaluate the feasibility of using the Diet ID™ platform to assess diet quality in breast cancer patients within a large integrated healthcare system. Methods: Eligible participants were women diagnosed with any stage of breast cancer within the past 24 months and receiving care at Kaiser Permanente San Francisco or Oakland. Recruitment is being conducted via email across three planned waves spaced three months apart, with the first wave launched in April 2025. Participants complete the Diet ID™ assessment online, with responses linked to electronic health records to capture additional demographic and clinical data. Feasibility metrics include recruitment yield, completion rates, and time to completion. Descriptive analyses summarize participant characteristics and HEI score distributions. Results: In the first wave, 1,349 potentially eligible patients were identified. After excluding 324 (24%) for reasons such as language preference, cognitive impairment, and lack of email, 1,021 were invited via email. Of those invited, 328 (32%) enrolled, with 93% completing the assessment in full. While enrollees were similar in age to invitees (mean = 58.9 vs. 60.7 years), White participants were overrepresented (62.8% enrolled vs. 47.0% invited) and Black/African American (5.8% vs. 13.7%), Asian/PI (18.6% vs. 23.4%), and Hispanic (6.4% vs. 8.0%) participants were underrepresented. Stage III/IV patients were also less likely to enroll (5.4% vs. 8.0%). Among 304 participants with complete dietary data, HEI scores ranged from 17 to 98 (mean ≈ 83, standard deviation ≈ 18) and were strongly right-skewed. Participants under age 50 were more common in the lowest HEI tertile (38%) than in the highest (27%). White participants were more likely to be in the top tertile (67% vs. 59% in the lowest), while Black/African American (5% vs. 9%) and Asian/PI (13% vs. 20%) participants were less represented. Higher HEI scores were linked to lower BMI: normal weight was more common in the top tertile (54% vs. 36%), while obesity was less prevalent (12% vs. 26%). Overall, about 15% of participants felt the tool did not accurately capture their diet, but dissatisfaction was more common in the lowest tertile (30%) compared to the highest (7%). Most participants found the tool quick (<5 minutes) and easy to use, with high acceptability (~85%). Results from the July and October waves will be included in the final analysis and presented at the conference. Conclusions: Preliminary findings suggest that Diet ID™ is a feasible and acceptable tool for assessing diet quality among breast cancer patients in clinical care. Early results show meaningful variation in diet quality and expected associations with BMI. However, the strong right skew in HEI scores highlights the need to assess the tool’s sensitivity to lower-quality diets. Ongoing data collection and follow-up will inform its broader use in dietary surveillance and survivorship care.

S. A. Roberts¹, A. L. Tin², J. Singh³, D. Lake³, E. Meditz⁴, A. Kulkarni⁵, M. Boparai⁶, B. Korc-Grodzicki⁶, A. Shahrokni⁶, K. Alexander⁶; ¹Internal Medicine, NewYork-Presbyterian Weill Cornell, NEW YORK, NY, ²Department of Statistics, Memorial Sloan Kettering Cancer Center, NEW YORK, NY, ³Department of Breast Oncology, Memorial Sloan Kettering Cancer Center, NEW YORK, NY, ⁴Department of Nutrition, Memorial Sloan Kettering Cancer Center, NEW YORK, NY, ⁵Department of Hematology and Oncology, Columbia University Irving Medical Center, NEW YORK, NY, ⁶Department of Geriatrics, Memorial Sloan Kettering Cancer Center, NEW YORK, NY.

Purpose: To assess which patient characteristics and elements of the GeriatricAssessment (GA) are associated with not proceeding to chemotherapy in older womenwith breast cancer.Methods: Between April 2022 and February 2024, 50 women aged 65 and older with breastcancer were seen in the Cancer and Aging Interdisciplinary Team clinic at our institution forGA prior to initiating systemic treatment. We present characteristics among our cohort andevaluate differences in GA domains between patients who proceeded to chemotherapyand those who did not.Results: When comparing the cohort of patients who did not undergo chemotherapy vsthose who did, factors that were significantly associated with the decision to omitchemotherapy included older age (median 84 vs 75 years old, p<0.001), non-triple negativedisease (75% vs 42%, p=0.035), frailty (94% vs 55%, p=0.007), abnormal functionalperformance test (75% vs 19%, p<0.001), high risk CARG-TT score (50% vs 13%, p=0.007),chemotherapy not recommended by geriatrician (69% vs 0%, p<0.001), iADL dependency(88% vs 44%, p=0.047), KPS<80 (75% vs 19%, p=0.003), and limited social activity (100% vs52%, p=0.015). Of the women who proceeded to chemotherapy, 42% underwent upfrontchemotherapy modifications.Conclusion: Our study identified components of the GA associated with chemotherapydecisions and modifications in older women with breast cancer. Further research isneeded to determine the causal relationships between GA components and decision-making and evaluate how such decision-making could be improved.

D. Chelysheva, J. Fanizza, E. Nasrollahi, E. Aguilar Montoya; Internal Medicine, UPMC Harrisburg, Harrisburg, PA.

Background Metastatic breast cancer (MBC) is an advanced stage of disease with a poor prognosis and heavy symptom burden. Its five-year relative survival rate is about 30%, and the median survival time is roughly 2-3 years. Palliative care can alleviate symptoms and improve quality of life in advanced cancer, and major oncology guidelines (ASCO/ESMO) now recommend providing specialized palliative care early in the course of metastatic illness. However, in real-world practice palliative care is often introduced very late. This study examines how delayed palliative care referral affects outcomes in MBC and makes the case for earlier integration. Methods We conducted a retrospective cohort study using data from the TriNetX global health research network, which includes de-identified electronic health records from multiple healthcare organizations, predominantly located in the United States. Female patients who were diagnosed with stage IV (metastatic) breast cancer between 2011 and 2024 were included. The primary focus of the analysis was to assess the time interval between metastatic diagnosis and receipt of a palliative care consultation. Additional variables collected included demographics and documented clinical symptoms. Patients were grouped based on whether or not they received a palliative care consultation, and matched cohort analysis was performed to compare symptom burden between the groups. Results A total of 1036 women with stage IV breast cancer were included. The median age was 66 years (range 30-90; SD = 13). The median time from metastatic diagnosis to first palliative care consult was 408 days, indicating that referrals generally occurred late in the disease course. Notably, median referral delays varied by race: 425 days for White patients, 347 days for Black or African American patients, 699 days for Asian patients, 294 days for Hispanic or Latino patients and 388 days for American Indian/Alaska Native patients. When we analyzed matched cohorts of patients who did and did not receive palliative care consultations, it was discovered that symptom burden was significantly higher in the palliative care group. This included symptoms such as pain, fatigue, delirium, and dyspnea. Conclusions These results highlight that palliative care is frequently introduced late for patients with metastatic breast cancer. Earlier integration, ideally soon after stage IV diagnosis, is advocated in guidelines and has the potential to improve symptom control, enhance quality of life, and align care with patient goals. In our cohort, the median time to palliative care referral was over a year from diagnosis. These findings align with prior studies and underscore that late palliative care referral may limit its impact on meaningful outcomes. The observed racial differences in timing further suggest a need to address systemic and cultural barriers to equitable, timely access. Additionally, the significantly higher symptom burden observed in the palliative care group supports the concern that referrals are often made reactively, in response to advanced clinical decline. Overall, our findings reinforce that palliative care should be embedded earlier in the treatment trajectory – not as a last resort, but as a concurrent component of comprehensive cancer

K. M. Cronin¹, J. Fasano², C. Shapiro³, G. Montgomery⁴, s. julie⁴, a. tiersten⁴, a. bhardwaj⁴, h. irie⁴, p. klein⁴, a. goel⁴, t. sheng⁴, t. shao⁴; ¹internal medicine, mt sinai west, New York, NY, ²Oncology, Mt Sinai Hospital, New York, NY, ³internal medicine, Mt sinai, New York, NY, ⁴internal medicine, mt sinai, New York, NY.

Background:Adjuvant chemotherapy for early-stage breast cancer is associated with numerous side effects, including nausea, fatigue, and neuropathy, which may lead to early discontinuation. Psychosocial variables may influence how patients experience and tolerate these side effects. Personality traits such as optimism and neuroticism at diagnosis may impact psychosocial outcomes and recurrence in long-term survivors. Optimism has been linked to better coping, reduced anxiety, and greater resilience, whereas neuroticism correlates with distress and poor coping. No prior studies have directly examined the relationship between optimism, coping, and chemotherapy side effects. This study aimed to evaluate whether psychosocial factors are associated with chemotherapy-related side effects.Methods:We conducted a prospective study of women with stage I-III breast cancer receiving standard neoadjuvant or adjuvant chemotherapy. At baseline (prior to treatment), participants completed four psychosocial questionnaires: the Revised Life Orientation Test (LOT-R), NEO-Five Factor Inventory Neuroticism Scale (NEO-N), Connor-Davidson Resilience Scale 10 (CD-RISC 10), and Brief COPE (B-COPE). Patients also completed the PRO-CTCAE v1 and PROMIS surveys at baseline, during chemotherapy, end of treatment, and one year post-therapy. The primary endpoint was to determine correlations between optimism, coping, and resilience with treatment-related toxicity (PRO-CTCAE). The secondary endpoint was to examine associations between psychosocial factors and physical, mental, and social domains of health-related quality of life (HRQOL). Spearman correlations assessed relationships between psychosocial and symptom scores. Linear mixed-effects models evaluated longitudinal associations, with time point and psychosocial variables as fixed effects and participant as a random intercept. Analyses were conducted in R (v4.4.0).Results:A total of 107 patients were enrolled (median age: 51 [range 42-58]). The cohort was diverse: 18.7% Hispanic, 37.3% White, 24.3% Black, 10.3% Asian, and 9.3% other. Symptom scores increased significantly by the end of chemotherapy compared to baseline (Estimate = 0.49, p < 0.01). Higher optimism was modestly associated with lower symptom burden (Estimate = -0.03, p = 0.05). Resilience was not significantly associated with symptom scores. Greater use of coping strategies was linked to higher symptom burden (Estimate = 0.02, p < 0.01), possibly reflecting increased efforts to manage symptoms. No specific coping strategy was significantly associated with symptom scores. Symptom burden increased during and shortly after chemotherapy but declined one year later. In the mixed-effects model, none of the psychosocial scores (optimism, coping, or resilience) remained significantly associated with symptom burden over time.Conclusions:Patients with higher optimism experienced fewer chemotherapy-related side effects, suggesting that optimism may serve as a potential psychological marker for reduced treatment burden. Greater coping effort was observed in those reporting higher symptom scores, possibly indicating a reactive coping response. These findings may inform future development of behavioral interventions aimed at reducing chemotherapy-related side effects in breast cancer patients.

C. Cao¹, T. Shao², A. Tsang¹, M. Kwa³, R. Brown⁴, L. Chen⁵, M. Schwartz⁶, D. Roblin⁷, M. H. Antoni⁸, L. Hilakivi-Clarke⁹, G. Kowk¹⁰, A. Lin⁹, K. Joseph³, J. X. Osorio⁶, J. H. Wang⁶, S. Cai¹; ¹Surgery, Mount Sinai Hospital, New York, NY, ²Hematology & Oncology, Mount Sinai Hospital, New York, NY, ³NYU Perlmutter Cancer Center, New York University Langone Health, New York, NY, ⁴Clinical Health Science, University of Wisconsin–Madison, Madison, WI, ⁵School of Public Health, Texas A&M University, College Station, TX, ⁶Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, ⁷Mid-Atlantic Permanente Research Institute, Kaiser Permanente, Rockville, MD, ⁸Psychology, University of Miami, Miami, FL, ⁹Hormel Institute, University of Minnesota, Austin, MN, ¹⁰Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ.

INTRODUCTION: Increased physical activity (PA) in breast cancer patients has been associated with multiple benefits including lower fatigue, depression and anxiety levels, better tolerance of treatment related side effects, and lower cancer recurrence rates (1). The American Cancer Society recommends that cancer survivors undergo at least 150-300 minutes of moderate intensity activity or 75-150 minutes of vigorous activity per week and encourages meeting or exceeding these upper limits (2). Given limited data on PA in Chinese American breast cancer survivors, this study aimed to evaluate and better quantify PA in this population. METHODS: As a part of a broader prospective cohort study investigating survivorship in Chinese American breast cancer patients compared to Non-Hispanic white (NHW) patients over a 12-month period, participants underwent a baseline phone survey administered by trained staff. All participants were women aged over 18, diagnosed with stage 0-III breast cancer within 10 years, and had completed primary surgical or medical treatment. The survey included the Global Physical Activity Questionnaire developed by World Health Organization (WHO), which was used to evaluate time spent on moderate and vigorous activity during work, travel and leisure and to calculate weekly metabolic equivalent (MET) minutes per week for each group. Group differences were evaluated using T-tests for significance. RESULTS: A total of 133 NHW and 110 Chinese American patients completed the baseline survey. The average age was 56 for Chinese Americans and 59 for NHWs, and the difference was not statistically significant. The average BMI of Chinese Americans (23.6) was statistically significantly lower than that of NHWs (25.7). Chinese Americans spent an average of 71 minutes per week on vigorous activity and 424 minutes per week on moderate activity compared to NHWs who spent an average of 179 minutes per week and 627 minutes per week, respectively. Combined, Chinese Americans averaged 2266 MET-minutes per week, while NHWs averaged 3952 MET-minutes per week, this difference was statistically significant (p = 0.0053). Additionally, for patients reporting use of a step counter, the average daily step count for Chinese Americans was 6592 compared to 8432 for NHWs. The reported average daily sedentary time for Chinese Americans (337 minutes) was not statistically different from that for NHWs (348 minutes). CONCLUSION: While both groups exceeded recommended PA minimums, Chinese American women with breast cancer self-reported significantly lower levels of PA than their NHW counterparts. Further studies should focus on the impact of this discrepancy on survivorship and possible interventions to bridge the gap between the two groups to mitigate health disparity after breast cancer treatment. KEYWORDS: breast cancer; survivorship; exercise; disparity SOURCES:(1) Le Y, Gao Z, Gomez SL, Pope Z, Dong R, Allen L, Chang MW, Wang JH. Acculturation and Adherence to Physical Activity Recommendations Among Chinese American and Non-Hispanic White Breast Cancer Survivors. J Immigr Minor Health. 2019 Feb;21(1):80-88. doi: 10.1007/s10903-018-0721-x. PMID: 29569102; PMCID: PMC6151158. (2) Rock CL, Thomson C, Gansler T, Gapstur SM, McCullough ML, Patel AV, Andrews KS, Bandera EV, Spees CK, Robien K, Hartman S, Sullivan K, Grant BL, Hamilton KK, Kushi LH, Caan BJ, Kibbe D, Black JD, Wiedt TL, McMahon C, Sloan K, Doyle C. American Cancer Society guideline for diet and physical activity for cancer prevention. CA Cancer J Clin. 2020 Jul;70(4):245-271. doi: 10.3322/caac.21591. Epub 2020 Jun 9. PMID: 32515498.

S. Casla¹, M. Castellanos-Montealegre², L. Cantero³, M. Ayuso-Chico⁴, J. Haro⁵, Ejercicio y Cáncer; ¹Escuela Enfermería y Fisioterapia, Universidad Pontificia Comillas, Ciempozuelos, SPAIN, ²Ciencias de la Actividad Física y el Deporte, Universidad de Castilla-La Mancha, Toledo, SPAIN, ³Centro Retiro, Centro Ejercicio y Cáncer, Madrid, SPAIN, ⁴Centro Cádiz, Centro Ejercicio y Cáncer, Madrid, SPAIN, ⁵Retiro, Centro Ejercicio y Cáncer, Madrid, SPAIN.

Multimodal Exercise in Breast Cancer: Health Impact and Efficacy of Online Modalities. RCTIntroductionExercise is widely recognized for its significant benefits in cancer survivors, helping improve cardiorespiratory fitness (CRF), reduce fatigue, and positively impact body composition. These advantages are crucial as cancer treatments often lead to reduced physical function and increased fatigue, negatively affecting quality of life (1,2). While traditional supervised exercise programs are effective, access remains a challenge due to logistical barriers. Therefore, exploring remote exercise options is essential for broader accessibility (3,4). This study evaluated the effectiveness and feasibility of a 16-week multimodal exercise intervention comparing online and onsite formats for breast cancer survivors at stages IA to IIIB.MethodologyThe study was conducted as a randomized controlled trial with 83 participants divided into intervention and control groups. The intervention group was further split into online and onsite subgroups, participating in aerobic, strength, and flexibility exercises. The primary outcomes measured were CRF (using the Bruce test) and body composition (via bioelectrical impedance). Secondary outcomes included functional capacity (sit-to-stand and 6-minute walk tests) and quality of life.Results demonstrated a 22.4% improvement in CRF in the intervention group versus a 4.96% decrease in the control group. Functional capacity also improved significantly in both the online and onsite groups, showing the potential of remote programs to match in-person results (5,6). Body composition changes included a 5.24% increase in lean mass and a 10% decrease in fat mass, supporting evidence that exercise contributes to improved metabolic profiles and lower inflammation, reducing long-term cancer risks (7,8).ConclusionsThe discussion highlighted a high adherence rate of 95.3% across both modalities, underscoring the effectiveness of flexible delivery for maintaining engagement. The perfect adherence in the online group (100%) emphasized the potential for virtual programs to fit into patients’ lives, especially for those balancing responsibilities or facing geographic limitations (9). Limitations included the use of the Borg scale for intensity monitoring instead of more objective measures, suggesting future studies should include precise tools and examine active treatment phases (10).In conclusion, both online and in-person multimodal exercise interventions were effective in enhancing CRF, body composition, and functional capacity in breast cancer survivors. The innovative aspect of demonstrating equivalent results between modalities highlights the potential of flexible, personalized programs to improve access and adherence, ultimately influencing long-term survival and quality of life.

P. Amaral¹, G. Tosello², P. Silva Filho¹, E. Nahas¹, D. Buttros¹; ¹Pós-graduação em Tocoginecologia, FMB/UNESP, Botucatu/SP, BRAZIL, ²Mastologia, Intituto do Câncer Oeste Paulista, Presidente Prudente/SP, BRAZIL.

Introduction: The rising incidence of breast cancer, alongside decreased mortality rates and therapeutic advances, has led to an increasing population of breast cancer survivors. These individuals are susceptible to acute and chronic psychological distress. Mindfulness-based interventions have been proposed as integrative strategies to support mental health and well-being in this population. This study aimed to evaluate the effectiveness of mindfulness practices compared to standard care in improving the quality of life among women surviving breast cancer. Methods: A systematic review was conducted including randomized controlled trials (RCTs) involving women aged ≥18 years who had undergone treatment for breast cancer (surgery, radiotherapy, chemotherapy, or a combination), at any clinical stage, without psychiatric disorders, no prior mindfulness practice, and that assessed quality of life as a primary or secondary outcome. Studies not meeting these criteria were excluded. A comprehensive literature search was performed without language or date restrictions across PubMed, Embase, Scopus, Web of Science, CINAHL, SciELO, LILACS, Cochrane Library, WHO, and grey literature sources (Google Scholar, OpenGrey, ProQuest, and direct contact with field experts). Risk of bias was assessed using the RoB 2 tool. Standardized mean differences (SMD) were calculated for pooled effect estimates using R software. The certainty of evidence was evaluated using the GRADE framework. Results: Thirteen RCTs met inclusion criteria, comprising a total of 1,942 breast cancer survivors, of whom 1,016 received mindfulness interventions and 926 received standard care. Risk of bias was considered low across the included studies. Meta-analysis revealed that mindfulness practices resulted in a small but statistically significant improvement in quality of life (SMD = 0.33; 95%CI: 0.16 to 0.49). However, the certainty of evidence was rated as low due to moderate heterogeneity (I² = 65.9%), high risk of publication bias (funnel plot asymmetry and Egger’s test), and serious imprecision (confidence interval spanning trivial to small effect sizes). Discussion: Key limitations of this review include study heterogeneity, the predominance of Mindfulness-Based Stress Reduction (MBSR) as the primary intervention, limited representation of patients with metastatic disease, and possibly attenuated effects in those with early-stage tumors due to less intensive treatment regimens. Despite these limitations, mindfulness practices demonstrated potential benefits in enhancing quality of life and, due to their socioeconomic accessibility, may warrant clinical recommendation as part of survivorship care in breast cancer patients. Funding and Registration: This study did not receive external funding. The review protocol was registered with PROSPERO (CRD42024502665) on January 26, 2024.

V. Prado¹, D. Buttros¹, P. Amaral¹, G. Tosello², S. Rizzi¹, E. Nahas¹; ¹Pós-Graduação em Tocoginecologia, FMB/UNESP, Botucatu/SP, BRAZIL, ²Mastologia, Intituto do Câncer Oeste Paulista, Presidente Prudente/SP, BRAZIL.

Introduction: Women diagnosed with breast cancer exhibit an elevated risk of weight gain and metabolic dysfunctions, which are associated with a decline in overall and specific survival rates. Interdisciplinary assessment at the time of diagnosis can positively influence prognosis and survival. This study aimed to evaluate the impact of breast cancer diagnosis and treatment on the metabolic health and survival of women undergoing treatment for breast cancer. Methods: This was a single-center, prospective cohort study that included women with a recent diagnosis of breast cancer, aged ≥ 40 years, without metastatic disease or established cardiovascular disease, who were followed for the first two years after breast cancer diagnosis. The criteria used for the assessment of metabolic health/dysfunction were the presence of obesity (body mass index, BMI ≥ 30kg/m²), hypertension (blood pressure, BP ≥ 130/85mmHg), hypertriglyceridemia (triglycerides, TG ≥ 150mg/dL), low high-density lipoprotein cholesterol (HDL 100mg/dL), and the presence of metabolic syndrome (MetS, NCEP-ATPIII criteria). Clinical and anthropometric data (BP, BMI, and waist circumference/WC) were collected through interviews and physical examinations. Information on oncological treatments and tumor characteristics was extracted from medical records. Biochemical analyses included total cholesterol, HDL, LDL, TG, and glucose levels. Patients underwent interdisciplinary assessment (nutritional and psychological) at the time of diagnosis and continued with follow-up appointments with a breast specialist according to the service routine for 2 years. Assessments were conducted at five time points: initial consultation, and at six, 12, 18, and 24 months. Statistical analyses included non-parametric tests, logistic regression, and Kaplan-Meier survival analysis. Results: A total of 165 women were eligible for the study, of whom 39 dropped out during follow-up. The analysis included 126 women with a mean age of 59.0 ± 12.0 years and a mean BMI of 29.7 ± 5.8 kg/m²; 91% of tumors were in stages I and II, 71% had negative axillary lymph nodes, and 79% were luminal subtypes. Over the 2-year follow-up period, among the indicators of metabolic dysfunction, a significant reduction was observed in the occurrence of women with dysglycemia (p=0.04), elevated systolic blood pressure (p0.05). During follow-up, 15 patients died, and these patients had a higher prevalence of MS at initial assessment (73% versus 41% of survivors, p=0.020) and higher glucose levels (p=0.021) compared to survivors. The presence of MS was associated with lower survival (p=0.021), with a Hazard Ratio of 9.09 (95% CI: 1.73-47.9). Conclusions: In women with breast cancer, interdisciplinary follow-up and healthy lifestyle recommendations had a positive impact on metabolic health, specifically on glycemia, HDL levels, and blood pressure, without altering the occurrence of obesity and MetS. MetS presented a high prevalence and was associated with lower survival.

F. Turenne¹, J. Merci², C. Mannley², G. Benoit², M. Guerrier², W. Guerrier², K. Dubique³, S. Estanis³, E. Durkin⁴, T. Fadelu⁵; ¹Surgery, University Hospital Mirebalais/ Zanmi Lasante, Mirebalais, HAITI, ²Oncology, University Hospital Mirebalais/ Zanmi Lasante, Mirebalais, HAITI, ³Research, University Hospital Mirebalais/ Zanmi Lasante, Mirebalais, HAITI, ⁴Oncology, Partners In Health, Boston, MA, ⁵Medical Oncology, Dana-Farber Cancer Institute, Boston, MA.

Background: Breast cancer remains the leading cause of female cancer mortality in low- human development index countries, including in Haiti. Treatment of breast cancer can impact patient’s quality of life (QOL). At the University Hospital of Mirebalais (HUM) in Haiti, due to the national absence of radiation therapy, patients treated with curative intent receive modified radical mastectomy (MRM) and systemic therapy with chemotherapy and hormonal therapy, as clinically indicated. This project aimed to measure QOL in women after breast cancer surgery. Methods: We conducted a cross-sectional study in adult women with pathologically-confirmed breast cancer and who underwent MRM at HUM between January 2018 to December 2022. Clinical and treatment data were collected from the electronic medical records and paper charts, while a comprehensive survey was administered assessing QOL and potentially associated factors. Functional Assessment of Cancer Therapy- Breast (FACT-B) 37-item questionnaire was used to assess the following domains: physical, emotional, social, and functional well-being, as well as breast cancer specific concerns; total score range is from 0-148, with higher scores representing better QOL. Hospital anxiety and depression scale (HADS) was also administered. These questionnaires were chosen due to broad use and prior validation in multiple settings; they underwent linguistic translation into Haitian Creole. Data were securely collected using Research Electronic Data Capture (REDCap) and Epi-Info version 7.2.5.0 was utilized for data analysis. QOL data were summarized descriptively in aggregate and by domain, groups were compared using non-parametric comparisons tests (Mann-Whitney and Kruskal-Wallis tests) and logistic regressions to explore potential predictors of anxiety and depression (cut-offs: HADS-A ≥8 for mild anxiety, HADS-D ≥15 for severe depression). Results: The study recruited 87 participants. The median age of the participants was 50 (interquartile range (IQR): 43-58). Educational attainment was modest, with 27 (31%) patients having only primary school level education and 41 (47%) patients reaching secondary school level. Most of the patients resided in the West department (60, 69%), most were post-menopausal (71, 82%), and 35 (40%) were married. Most patients (58, 67%) had locally advanced tumors, and majority (60, 69%) had an ECOG performance status of 1. Within this cohort, 86 (99%) received chemotherapy, and 78 (91%) received hormonal therapy. The total FACT-B score among all patients had a median of 111.5 (IQR: 97.2-122.7), reflecting generally good perceived quality of life. In summary, most demographic and clinical variables were not statistically significantly associated with QOL, except emotional well-being was notably lower among younger women (<50 years), and receipt of both neo- and adjuvant chemotherapy appeared to be negatively associated with well-being in aggregate and across multiple domains (physical, emotional and breast specific well-being). The total median HADS anxiety score was 8 (IQR: 6-11) and a depression score was 13 (IQR: 12-15), indicating at least mild anxiety and moderate to severe depression in most of the cohort. Again younger age (<50) was associated with higher rates of anxiety, while there was no clear association trend with depression among the factors that were explored. Conclusions: This study provides a summary of QOL and the prevalence of anxiety and depression among Haitian patients who underwent MRM. Younger patients had worse emotional well-being and more anxiety. The high prevalence of at least moderate depression in over 50% of patients indicates unmet psychosocial needs in this underserved population. The study highlights the need for improved mental health services for patients with breast cancer, especially for younger patients.

N. Jahan¹, E. Stringer-Reasor¹, T. Padalkar¹, K. Khoury¹, M. Escobar¹, C. P. Williams², I. Starks¹, H. Sarfraz¹, A. Falcao¹, N. Henderson¹, S. Olisakwe¹, K. Keene³, A. Azuero⁴, M. E. Melisko⁵, E. H. Shinn⁶, G. B. Rocque¹; ¹Division of Hematology and Oncology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, ²Department of Medicine, University of Alabama at Birmingham, Birmingham, AL, ³Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, ⁴UAB School of Nursing, University of Alabama at Birmingham, Birmingham, AL, ⁵Division of Hematology and Oncology, University of California San Francisco, San Francisco, CA, ⁶Division of Cancer Prevention and Population Sciences, The University of Texas MD Anderson Cancer Center, Houston, TX.

Background: Metastatic breast cancer (MBC) and its therapies can cause a myriad of sexual problems, which often go unaddressed. There is limited information on how women with MBC would like to communicate the sexual problems that may arise from their ongoing cancer therapy. Methods: This qualitative study explored the perspectives on sexual health communication preferences of women with MBC. A medical anthropologist conducted semi-structured interviews with women diagnosed with MBC at the University of Alabama at Birmingham from September 2024 to May 2025 via Zoom, phone, or in-person meetings. Interviews were transcribed verbatim and inductively coded using Dedoose software to identify recurring themes and exemplary quotes. Results: Of 20 interviewed women aged 30-77, 11 (55%) were White and 9 (45%) were African American; 95% were heterosexual and 1 (5%) was bisexual; 10 (50%) were married or partnered and 10 (50%) were widowed, single, or divorced; and 90% were in menopause (natural or treatment-related). Six key themes emerged from interviews (Table). First, women with MBC emphasized normalizing the conversation about sexual problems in the clinical setting and permitting women to bring sexual problems to providers. “Being comfortable with the conversation and making it not seem like it’s something that’s taboo, that then can help patients feel more comfortable talking about something that they may feel is taboo to talk about with.” Second, they recommended self-review materials, such as flyers, pamphlets, or web pages, that include expected sexual consequences of their cancer treatments to improve their knowledge and set realistic expectations. “Yeah and would be much more comfortable just reading about it rather than asking about it. And then once they read about it and knew that yes, there was a lot of people had this problem, I think that they could then they could be more open to talking about it to the doctor.” They preferred receiving information close to diagnosis and intermittent check-ups afterward. “If the doctor brought it up early on, and then the doctor could ask maybe on the second or third visit.” Women differed in their preferences for patient-initiated versus provider-initiated conversations, suggesting the use of a brief survey to gauge comfort levels and tailor the approach accordingly. “I think do a little survey or something to see if they are interested.” There was no consensus on the preferred provider to discuss sexual problems. Notably, most women preferred not to include their spouses in the initial conversation. “I also think that it should be brought up maybe the first time when the partner is not present.” Conclusions: Women with MBC recommended normalizing the conversation about sexual problems with the availability of evidence-based self-review materials to be delivered close to diagnosis and intermittently afterward. Further work is needed to apply these recommendations in clinical settings.

M. C. Carvalho, I. d. Oliveira, B. C. Figueroa, T. C. Lima, R. P. Souza, S. M. Sanches, V. C. Lima, M. G. Cesca; Clinical Oncology, AC CAMARGO CANCER CENTER, São Paulo, BRAZIL.

Background: Endocrine therapy (ET) is the cornerstone of hormone-receptor positive (HR+) breast cancer treatment. However, it is potentially associated with several adverse events, which can impact patients’ quality of life (QoL). Depicting different spheres of QoL affected by ET is essential to improve supportive care strategies. This study aimed to evaluate QoL among breast cancer patients on mid/long-term ET, exploring its diverse domains. Methods: Single-center, observational cohort study. Female patients with HR+ breast cancer undergoing systemic ET for at least 6 months were included. Participants fulfilled a unique online questionnaire, including the validated European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) + Breast Cancer-specific Module (BR23). QoL was assessed across several functioning and symptom domains. Each score domain was transformed into a score ranging 0 to 100, according to EORTC guidelines. Higher scores indicated a better quality of life for functioning domains/general health status, and a greater symptom burden. Descriptive statistics were used to characterize the domains (mean scores) and the population characteristics. Correlations between the patient’s characteristics and the scores were evaluated with Student’s T test. Results: 200 patients, with a median age of 44 years-old (range: 27-92), were included. The majority had at least higher education (87%), were self-declared as white (69%; brown/black: 24.5%), heterosexual (95.5%), were premenopausal (74.5%), overweight (68%) and had children (69.5%). 14% were under ET for metastatic disease (86% adjuvant ET), 94.5% had primary breast cancer surgery (50.5% conservative) and 49% breast reconstructive surgery. Chemotherapy was used in 62.5% and the ongoing ETs were: SERMs (22.5%), aromatase inhibitors (70.5%) and SERDs (7%); 58.5% associated with ovarian function suppression. Global health status (71.4) and physical and role functioning (76.9 and 71.8) were relatively well preserved in this cohort. Financial difficulties (25.7), and symptoms related to surgery, such as breast (23.3) and arm (31.9) pain were also not impactful. However, patients had significant impairment in sexual functioning (27.4), future perspective (27.5), body image (56.6) and in emotional (51.3) and cognitive (52.9) functioning. Insomnia (52.0) and fatigue (40.1) were the most impactful symptoms. Premenopausal status was correlated to worse body image (52.9 vs 67.1; p=0.014) and emotional functioning (49.4 vs 56.9; p=0.006). There was a trend for worse body image in patients who underwent breast reconstructive surgery (46.9 vs 66.5; p=0.055), worse sexual functioning for aromatase inhibitors versus SERMs (25.9 vs 32.6; p=0.059) and worse global health status in premenopausal women (70.1 vs 75.2; p=0.058). Conclusion: This study highlights the impact of ET and breast cancer diagnosis in the sexual, cognitive and emotional functioning, as well in the future perspective and body image of HR+ breast cancer patients. Premenopausal women appear to be the most affected. These insights underscore the importance of routine QoL assessment in clinical practice, and the urgent need for improvement in survivorship care for breast cancer patients.

J. Hundal¹, A. Loomba², M. Mody³, N. Lopetegui-Lia⁴; ¹Hematology and Oncology, Cleveland Clinic, Cleveland, OH, ²Hematology and Oncology, Maharaja Agrasen Medical College, Agroha, INDIA, ³Medicine, M. P. Shah Government Medical College, Bharuch, INDIA, ⁴Department of Internal Medicine, Division of Medical Oncology, Ohio State University, Columbus, OH.

Background: Patients with breast cancer (BC) often experience a range of treatment-related symptoms that significantly impact quality of life. Social media platforms such as Instagram have become popular sources of health information, including guidance on symptom management. However, unregulated nature of these platforms enables the rapid dissemination of health-related misinformation, which can influence patient behavior and decision-making. Despite this growing concern, limited data exist on the scope and nature of symptom-related misinformation in the context of BC. This study aimed to evaluate the prevalence, characteristics, and engagement patterns of misinformation related to BC symptom management on Instagram.Methods:We conducted a cross-sectional content analysis of publicly available Instagram posts to evaluate the prevalence and nature of misinformation related to symptom management in BC. Searches using breast cancer-related and symptom-specific hashtags (e.g., #cancerfatigue) were conducted between June 17-28, 2025. To reduce algorithmic bias, searches were done in incognito mode. Posts were eligible if in English, publicly accessible, referenced symptom management in the context of BC, and made a therapeutic claim. Posts unrelated to cancer or lacking health-related content were excluded. For each symptom, the first 30-50 eligible posts were included.For each post, data were extracted on symptom category, misinformation classification (accurate, misleading, false, or unproven), perceived risk level (none to high), creator type, emotional tone, follower count, engagement (likes/comments), and presence of promotional links. Two independent coders reviewed each post. Descriptive statistics summarized misinformation prevalence and engagement patterns. Thematic analysis of captions identified narratives conveying misinformation.Results:A total of 328 Instagram posts referencing BC symptom management were included, categorized by symptom: fatigue (n = 46), brain fog (n = 45), hair loss (n = 46), nausea (n = 48), neuropathy (n = 51), cancer pain (n = 44), and insomnia (n = 48). Misleading content was the most prevalent, comprising 55.2% posts (n=181), while accurate information was infrequent, with only 22.8% posts (n=75). Thematic analysis revealed that approximately 30% of posts referenced evidence-based interventions, while 50% promoted non-evidence-based therapies, such as “magic juices,” Ayurvedic cures, and commercial programs claiming to eliminate treatment side effects. Additionally, 20% of posts offered oversimplified advice, such as using ginger for nausea or turmeric for recurrence prevention.The predominant emotional tones were neutral (42%, n = 138) and hopeful (40%, n = 132). Commercial intent was noted in more than half of the posts (53%,n= 174).Despite 64% (n=210) accounts having >1,000 followers, overall engagement was low, with 82% (n=269) of posts receiving <100 likes and <30 comments. Additionally, 48.4% of the creators were influencers, compared to healthcare professionals, who comprised only 15%. Conclusion: Among Instagram posts addressing BC symptom management, misinformation was highly prevalent, with over half the content categorized as misleading and fewer than one-quarter considered accurate. Commercial intent was common, and non-medical influencers, rather than healthcare professionals, created a significant proportion of posts. Despite many accounts having large followings, overall user engagement remained low. These findings highlight the risk of widespread exposure to low-quality health information and underscore the need for greater engagement by oncology professionals and institutions to promote accurate, evidence-based content on social media platforms.

D. B. Lipps¹, K. Russell-Bertucci¹, S. M. Cain², P. L. Myers³, A. O. Momoh³, D. L. Hertz⁴; ¹School of Kineisology, University of Michigan, Ann Arbor, MI, ²Chemical and Biomedical Engineering, West Virginia University, Morgantown, WV, ³Plastic Surgery, University of Michigan, Ann Arbor, MI, ⁴College of Pharmacy, University of Michigan, Ann Arbor, MI.

Background: Upper extremity range of motion (UEROM) deficits are common after mastectomy and breast reconstruction, limiting patient recovery and quality of life. Many breast cancer patients report shoulder pain and reduced arm motion months to years post-surgery, including significant declines in abduction and flexion. However, access to frequent UEROM assessment in clinics is limited by time, equipment, and specialized expertise. A smartphone app could offer an accessible solution for at-home UEROM evaluation. We hypothesized that a smartphone application could detect reductions in shoulder abduction and flexion following breast reconstruction, yielding results comparable to those from wearable inertial measurement units (IMUs).Methods: Thirteen female breast cancer patients (mean age 45.5 years, range 35-54) completed at-home UEROM assessments both before and 6-12 weeks after mastectomy with immediate breast reconstruction. Participants performed the assessments simultaneously using an IMU sensor system (placed on sternum, right/left upper arms, right forearm, left forearm) and an iPhone application (MotionDetect module, CareEvolution, Ann Arbor, MI). The app provided standardized audio and video instructions, ensuring consistent arm positioning and movement. UEROM was defined as the maximum angle of abduction and flexion from the torso, measured both by the IMU and iPhone’s onboard sensors. Pairwise changes in pre- and post-surgery mobility were compared within and across both measuring methods using paired t-tests. Agreement between IMU and iPhone app measures was determined using Pearson correlations.Results: Both IMU and iPhone app measures detected significant declines in the maximum shoulder abduction and flexion following breast reconstruction. 30% of enrolled mastectomy patients exhibited clinically meaningful UEROM limitations exceeding 20 degrees post-surgery, consistent with prior studies. Specifically, the IMU detected significant decreases in abduction (p = 0.007) and flexion (p = 0.007), while the iPhone app detected significant reductions in flexion (p = 0.004) and a trend toward decreased abduction (p = 0.08). The pre-post difference in UEROM between the elevation angles derived by the IMU sensors and the iPhone app were statistically similar (both p > 0.15), with strong correlations between the IMUs and iPhone app measures in abduction (r = 0.92) and flexion ranges of motion (r = 0.96). Discussion: This study demonstrates that a smartphone app is able to detect and quantify upper extremity range of motion deficits following breast reconstruction surgery with comparable results to a wearable IMU sensor system. The app consistently identified significant post-operative decreases in shoulder mobility, suggesting it can serve as a convenient, accessible means for remote UEROM monitoring. These app-based assessments are far more scalable for use in clinical trials and practice than sensor-based assessments. The smartphone app’s ease of use may facilitate telehealth-based monitoring, enabling clinicians to intervene earlier and address mobility restrictions, which could potentially improve patient outcomes and quality of life.

N. M. Fleege¹, E. E. Chasco², L. Soweid², S. Houghton², A. T. Seaman³; ¹Department of Internal Medicine, Division of Hematology/Oncology, University of Iowa Health Care, Iowa City, IA, ²Institute for Clinical and Translational Science, University of Iowa, Iowa City, IA, ³Department of Internal Medicine, Division of General Internal Medicine, University of Iowa Health Care, Iowa City, IA.

Background: The prognosis for patients with metastatic breast cancer (MBC) has substantially improved due to advancement in therapies. With prolonged survival, patients’ caregivers often experience an extended duration of caregiving. However, little is known about the impact of a MBC diagnosis and treatment on caregivers, or on the caregiver-patient relationship over time. Using a dyadic approach, this study explored how patients with MBC and their caregivers perceive a MBC diagnosis and subsequent caregiving needs over time on an individual and dyadic level. Methods: Patient-caregiver dyads participated in semi-structured qualitative interviews from July 2024-March 2025. Informal caregiver was defined as an unpaid individual who provides at least 50% of a patient’s care needs. Patients and caregivers were interviewed separately. The interview guide included questions about patient and caregiver perspectives on and experiences with MBC diagnosis and treatment, unmet needs, and facilitators and barriers associated with caregiving. Interviews were audio-recorded and transcribed; transcripts were imported into the qualitative data management program MAXQDA and analyzed using an adapted framework method. Results: Eleven patient-caregiver dyads [consisting of opposite sex-spouse pairs (n = 7), same-sex spouse pair (n = 1), opposite-sex engaged pair (n =1), and daughter-mother pairs (n=2)] were interviewed. In relating participants’ experiences, four themes were developed: 1) contrast of a prior cancer diagnosis to current MBC experience, 2) concerns related to individual health after MBC diagnosis and its role in caregiving needs, 3) MBC as a shared diagnosis and experience, and 4) impact of MBC diagnosis on the dyadic relationship. Participants contrasted MBC with patients’ previous cancer diagnoses, which typically included a shorter, intense period of treatment followed by a return to normalcy. Conversely, for MBC, participants highlighted the uncertainty of the survival period, prolonged symptoms, and the realization that there would be no return to normalcy. Both patients and caregivers shared concerns about the impact of MBC on their individual health and its impact on the dyad. While patients focused on feelings of uncertainty regarding their own functioning, mortality and potential increase in caregiving needs over time, caregivers shared concerns about their health, age, and ability to provide a prolonged duration of caregiving. Caregivers often viewed MBC diagnosis/treatment as a shared experience, frequently using “we” or “our” in responses. An important topic was the impact of a MBC diagnosis and treatment on their shared activities as a dyad (i.e. socializing, traveling, and exercising together). Patients emphasized that caregivers needed time for hobbies and self-care, but caregivers were frequently concerned about leaving patients alone or traveling far. In terms of the dyadic relationship, both patients and caregivers described monitoring and managing the others’ emotions. Most participants agreed that the MBC diagnosis either hadn’t affected their relationship or had brought them closer. Conclusions: Caregiving changes clinical interpersonal dynamics by bringing an additional person into the clinical relationship. Given this, dyadic approaches are particularly useful as they provide insight into the unique perspectives and experiences of each dyad member and their influence on interpersonal processes. Understanding patient and caregiver perspectives and experiences of MBC diagnosis, treatment, and caregiving needs from both an individual and a dyadic perspective is essential to improving clinical care and quality of life for patients with MBC and their caregivers.

A. Haiderali¹, J. R. Earla², J. Nathani³, P. Singh⁴, S. Sharma⁴; ¹Value & Implementation, Merck, North Wales, PA, ²Value & Implementation, Merck, Rahway, NJ, ³HEOR, Parexel International, Bengaluru, INDIA, ⁴HEOR, Parexel International, Chandigarh, INDIA.

Objectives: This study focused on summarizing the quality of life (QoL), health state utility values, and patient-reported outcomes (PRO) associated with hormone receptor-positive (HR+) /human epidermal growth factor receptor 2-negative (HER2-) locally recurrent inoperable or metastatic breast cancer (BC). Methods: A PRISMA-compliant systematic literature review (SLR) was conducted to identify English language studies published from database inception till July 2024. Embase and MEDLINE databases were searched, along with recent conference proceedings (2021-2024) and bibliographies of relevant SLRs, to comprehensively identify the evidence. Results: Thirteen studies (sample sizes: 15-2,352; mean/median ages: 46.1-66 years; data collection period: 2010-2023) assessed QoL in HR+/HER2- metastatic BC patients across the Netherlands (1), Canada (2), Germany (1) and the USA (3) and multiple countries (6). These studies (9 cross-sectional, 4 longitudinal) primarily reported evidence for chemotherapy, hormonal, and targeted therapies. Patients with progressive disease (PD) health state had worse QoL compared to those in progression-free (PF) health state across most QoL/PRO scales. Lambert-Obry et al (2018) reported that in first-line (1L) and second and/or subsequent line (≥2L) settings, EQ-VAS (66.2 vs 76.8; 66.1 vs 71.7), EORTC QLQ-C30 Global Health Status (GHS) (52.9 vs 68.2; 54.0 vs 66.0), and EQ-5D utility scores (0.64 vs 0.73; 0.65 vs 0.74) were lower and BPI scores (3.1 vs 2.0; 2.6 vs 2.0) were higher for PD vs. PF patients. Lower scores on functional scales and EQ-VAS, and higher scores on symptom scales and BPI indicating worse QoL. QoL generally declined as patients progressed through treatment lines (Table 1). Functional scales (EORTC QLQ-C30 and QLQ-BR23) worsened, while symptom scales in both instruments increased, with fatigue significantly impacting PD vs. PF disease in 1L (43.1 vs 36.5) and 2L settings (45.2 vs 37.1) (Lambert-Obry 2018). FACT-G scores significantly declined in patients with visceral + bone metastases at 3- and 6-months vs baseline (-6.6 and -3.6, respectively, p<0.05) (De Laurentiis 2018). Lower scores were seen in patients with visceral + bone metastases (FACT-G: 57.7; FACT-B: 79.7) compared to those with bone-only (63.7; 88.7) or visceral-only metastases (60.9; 84.8) (Wood 2016). This impacted Physical Well-Being (FACT-G: 17.1 vs 19.1 vs 18.7), Emotional Well-Being (FACT-G: 12.0 vs 13.7 vs 13.1), and Breast Cancer Subscale domains (FACT-G: 22.2 vs 25.0 vs 23.7), in visceral + bone vs. bone only and visceral only groups (Wood 2016). The EQUALS survey reported fatigue (74-78%), joint pain (64%), and vaginal atrophy (56%) as the most impacted symptoms. 12-20% of patients reported poor or very poor QoL (Sammons 2023 and Sammons 2024). Conclusion: The present SLR on HR+/HER2- locally recurrent inoperable or metastatic BC revealed significant humanistic burden with declining QoL and increasing symptom burden through progressive treatment lines. These findings highlight the need for new treatments balancing efficacy and QoL, particularly for patients with limited treatment options.

M. C. Carvalho, M. G. Cesca, I. d. Oliveira, B. C. Figueroa, T. C. Lima, S. M. Sanches, V. C. Lima, R. P. Souza; Clinical Oncology, AC CAMARGO CANCER CENTER, São Paulo, BRAZIL.

Background: Breast cancer and its treatment significantly impact patients’ interpersonal relationships, with lasting effects. Adverse events of anticancer therapies, including sexual dysfunction and body image changes, frequently negatively affect patients’ quality of life and relationships. This study aimed to evaluate the incidence of relationship breakups (RBr) during endocrine therapy (ET) for breast cancer and its associated factors. Methods: This is a single-center, retrospective, observational cohort study. Participants were female ≥18 years-old, with hormone-receptor positive (HR+) breast cancer (metastatic or non-metastatic, including in situ neoplasia) undergoing ET for at least 6 months. Data were collected through an online questionnaire, which included demographic, relationship and quality of life aspects, and electronic medical records. The patients who reported being in a relationship at ET initiation were included in the primary outcome analysis. The primary endpoint was the incidence of RBr among those in a relationship at ET initiation. Secondary endpoints included factors associated with RBr and motivations for maintaining relationships. Descriptive statistics were used for describing the population characteristics and the endpoints. Chi-square or Fisher’s exact tests were used for determining categorical variables association. Results: Of 201 patients who completed the questionnaire, 162 were in a relationship at ET initiation, and were included in the primary analysis. The median age at diagnosis was 44 years-old (range: 26-71), and the majority worked outside home (74.1%), had at least higher education (86.4%), had children (72.8%), were premenopausal (75.9%) and overweight (67.9%). 13.6% had HER2+ tumors, 14.8% metastatic disease, and 6.8% in situ carcinomas. The ETs in use were: SERMs (23.5%), aromatase inhibitors (70.4%), and SERDs (6.2%). 58% received ovarian function suppression and 24.7% a target-therapy (24.1% iCDK4/6). 95.1% were heterosexual, 3.1% homosexual and 1.9% bisexual. 72.2% were married. Sixty-two (38.3%) reported a RBr after at least 6 months of ET. Among those, 35.4% (n=22) attributed the RBr to cancer treatment in general, and 27.4% (n=17) to ET. The RBr decision was made by the patient in 48.1% (n=13), by the partner in 37% (n=10), and by both in 14.8% (n=4). Some contributing factors to RBr were low libido (27.0%), sexual dissatisfaction (19.0%), prejudiced body image (22.2%), and difficulties in communication (20.6%). Only axillary node dissection was associated with RBr in univariate analysis (52.3% vs 33.3% for sentinel lymph node dissection; p=0.04). There was a trend of association between nulliparity and RBr (50% vs 33.9%; p=0.07). Despite 55.6% of responders referring to a conflictual RBr, 74.1% of patients who ended their relationships expected a lasting relationship in the future. Considering the 100 women who maintained their relationships, only 14% were dissatisfied with them. The main contributing factor for maintaining the relationship was affection (73%), with children (8%), financial aspects (2%), religion (2%), fear of loneliness (2%) and others (3%) being less relevant. Conclusion: Our findings reveal a considerable incidence of RBr among breast cancer patients undergoing ET, with more than one third of patients directly attributing the ending of the relationship to treatment. Factors such as libido, sexual satisfaction, body image, and communication were reported as crucial in this context of relationship vulnerability. This study underscores the urgent need to integrate psychosocial assessments and to offer targeted support to manage the impacts of ET/treatment on patients’ relational lives, aiming to preserve well-being and quality of life during and after breast cancer treatment.

V. Andion Camargo, F. Akkoc Mustafayev, M. Jaramillo, Z. Sarfraz, K. A. Qidwai, L. S. Spiegelman, M. S. Ahluwalia, R. L. Mahtani; Medical Oncology, Miami Cancer Institute, Baptist Health South Florida, Miami, FL.

Background: Breast cancer (BC) patients face a lifelong disease burden that includes significant psychological stress. While clinical trials often focus on treatment efficacy and physical toxicities, psychiatric side effects remain underrecognized despite their potential to impact quality of life, adherence, and outcomes. This study evaluated the extent to which psychiatric symptoms were monitored and reported in Phase III clinical trials of FDA-approved BC treatments over the past decade. Methods: We reviewed the FDA archives to identify BC treatments approved over the past decade and found 21 such treatments. We conducted a search on clinicaltrials.gov to identify Phase III trials evaluating these FDA-approved interventions initiated after January 1, 2015, with posted results. The search yielded 38 clinical trials, comprising a total of 26,298 participants. We then examined each trial cohort for the presence of reported psychiatric symptoms. Trial protocols were reviewed in detail to identify the specific assessment tools and criteria for monitoring psychiatric symptoms, including documentation during treatment and post-treatment follow-up. All symptoms were recorded as adverse events for each trial per the NCI CTCAE guidelines. Most trials reported symptoms only during the treatment period. Descriptive statistics were used for data analysis. Results: Among the 38 phase III trials, 37 (97%) reported at least one psychiatric symptom. The most frequently reported symptom was insomnia, affecting 2563 participants (9.7%), while nervousness was the least reported, documented in only 1 participant. Other reported symptoms included anxiety, stress, depression, suicide attempts or completions, and confusional states. The most used assessment tool was EORTC-QLQ C30, followed by EQ-5D-5L, NCI-PRO-CTCAE, and FACT-B. Additional psychiatric symptoms, such as disorientation, apathy, panic attacks, stress, mania, psychiatric decompensation, mental disorders and sleep disorders, were identified but inconsistently assessed across trials. Most trials recorded psychiatric symptoms only during the treatment period, with limited documentation in long-term follow-up. Conclusion: While most trials reported at least one psychiatric symptom, monitoring was largely limited to short-term effects, highlighting the narrow scope of assessment. Inconsistent use of tools and limited follow-up suggest psychiatric symptoms remain underrecognized. This study is limited by reliance on publicly available data and potential reporting bias. A more holistic and longitudinal approach to psychiatric symptom monitoring can significantly improve patient safety to ensure treatment adherence without compromising their well-being.

L. Yang¹, T. Tayyab², R. Kokts-Porietis², Q. Wang², J. McNeil³, M. Matthews⁴, L. Dickau², J. Vallance⁵, M. McNeely⁶, N. Culos-Reed⁷, K. Kopciuk², K. Courneya⁸, C. Friedenreich¹; ¹Oncology, University of Calgary, Calgary, AB, CANADA, ²Cancer epidemiology and prevention research, Alberta Health Services, Calgary, AB, CANADA, ³Kinesiology, University of North Carolina at Greensboro, Greensboro, NC, ⁴Metabolic Epidemiology Branch, National Cancer Institute, Rockville, MD, ⁵Faculty of Health Disciplines, Athabasca University, Athabasca, AB, CANADA, ⁶Physical therapy, University of Alberta, Edmonton, AB, CANADA, ⁷Kinesiology, University of Calgary, Calgary, AB, CANADA, ⁸Faculty of Kinesiology, Sport, and Recreation, University of Alberta, Edmonton, AB, CANADA.

Background: Sleep problems are common among breast cancer survivors and are associated with poor quality of life. Yet, few studies have accounted for depression. This study examines whether depressive symptoms attenuate the association between sleep and quality of life in newly diagnosed breast cancer survivors. Methods: Women with newly diagnosed early-stage breast cancer were recruited between 2012-2019 in Alberta, Canada, and completed the Pittsburgh Sleep Quality Index (PSQI) to assess global sleep quality. Quality of life was measured using the Short Form Survey (SF-36 version-2) to assess physical and mental well-being. Depressive symptoms were measured using the Patient Health Questionnaire (PHQ-9). Multivariable linear regressions were used to estimate the association of sleep measures with physical and mental well-being. Depressive symptoms were evaluated as a potential confounder and effect modifier. Results: Among 1454 breast cancer survivors with available data, 43% reported poor global sleep quality and 10.5% reported clinically meaningful depressive symptoms. Poor sleep quality was associated with lower physical (β=-3.0, 95%CI: -3.8 to -2.3) and mental well-being (β=-5.7, 95%CI: -6.7 to -4.7). These associations were attenuated to (β=-2.3, 95%CI: -3.1 to 1.5) and (β=-1.2, 95%CI: -2.1 to -0.3) after further adjusting for depression symptoms. Stratified analyses showed a slightly stronger association in women with non-minimal symptoms, though this association was not clinically meaningful. Conclusion: The association between sleep and quality of life was substantially attenuated after accounting for depressive symptoms. Longitudinal data are needed to clarify the temporal relationship and determine whether sleep can serve as an early indicator of emerging depression. Next steps: Based on these findings, we are currently investigating depressive symptoms as a mediator for the association between sleep health and quality of life, using longitudinal data collected from time of diagnosis to five-years follow-up. We will be able to complete the analyses and report findings from the mediation analyses at the time of conference.

F. P. Pons-Faudoa¹, F. Mesa-Chavez¹, A. Platas², B. F. Vaca-Cartagena¹, A. S. Ferrigno³, A. Fonseca⁴, M. Miaja⁴, M. Cruz-Ramos⁴, J. E. Bargallo-Rocha⁵, P. Cabrera-Galeana⁶, A. Mohar⁷, C. Villarreal-Garza¹; ¹Breast Cancer Center, Hospital Zambrano Hellion TecSalud, Tecnologico de Monterrey, San Pedro Garza Garcia, MEXICO, ²Escuela de Medicina y Ciencias de la Salud, Tecnologico de Monterrey, Mexico City, MEXICO, ³Department of Medicine, Yale University School of Medicine, New Haven, CT, ⁴Joven & Fuerte, Programa para la Atencion e Investigacion para Pacientes Jovenes con Cancer de Mama, MILC, Mexico City, MEXICO, ⁵Joven & Fuerte, Programa para la Atencion e Investigacion para Pacientes Jovenes con Cancer de Mama, MILC, San Pedro Garza Garcia, MEXICO, ⁶Breast Medical Oncology Unit, Instituto Nacional de Cancerologia, Mexico City, MEXICO, ⁷Epidemiology Unit, Instituto Nacional de Cancerologia, Mexico City, MEXICO.

Background: Breast cancer (BC) diagnosis and treatment can significantly disrupt employment, reproductive, and health behaviors, particularly in young women, with lasting implications for quality of life. However, longitudinal data in Latin American populations remain scarce. This study aimed to characterize five-year sociodemographic and lifestyle trajectories among Mexican young women with BC (YWBC). Methods: Females aged ≤40 years diagnosed with stage I–III BC between 2015 and 2020 were enrolled in the Joven & Fuerte prospective multicenter cohort. Sociodemographic and lifestyle variables including occupational status, income, relationship status, fertility preferences and outcomes, and behaviors such as exercise, alcohol use, smoking, and spirituality were assessed using generalized estimating equations and multinomial logistic regression. Risk ratios (RR), relative risk ratios (RRR), and 95% confidence intervals (CI) were calculated relative to baseline. Data were collected at diagnosis, 6 months, 1 year, 2–3 years, and 4–5 years post-diagnosis. Due to the longitudinal design, missing data varied by variable and timepoint. Each analysis was calculated based on the number of respondents with available. Results: Among 526 participants (median age: 36 years; IQR: 32–38), 52.9% had education up to high school. At diagnosis, ~40% were employed full- or part-time. Employment dropped at 6 months (RR = 0.46; 95% CI: 0.41–0.51) and 1 year (RR = 0.54; 95% CI: 0.49–0.60), both p < 0.001. Occupational changes, reported by 70% at diagnosis, increased at 2–3 years (RR = 1.15; 95% CI: 1.05-1.26; p = 0.003) and 4–5 years (RR = 1.23; 95% CI: 1.12-1.34; p < 0.001). Income reductions affected 67% at diagnosis and persisted, though likelihood declined at 4–5 years (RR = 0.74; 95% CI: 0.62–0.89; p = 0.001), suggesting partial financial recovery. Relationship status was stable: 78% had a partner at diagnosis; 75% stayed with the same partner at 6 months, and 68% at 4–5 years. Compared to this group, being with a different partner at 1 year (RRR = 0.24; 95% CI: 0.10–0.56; p < 0.001) or starting a new relationship at 2–3 years after being single (RRR = 0.31; 95% CI: 0.14–0.72; p = 0.006) was less likely. Fertility preferences declined: 39% desired biological children at diagnosis vs. 20% at 4–5 years (RR = 0.40; 95% CI: 0.17-0.95; p = 0.038). Fewer than 10 live births occurred, and most patients (95-99%) reported no attempts to conceive, with no significant change over time. Lifestyle behaviors improved during the study period. Physical inactivity dropped from 57% at diagnosis to 44% at 4–5 years. At follow-up participants were more likely to engage in <150 min/week (RRR = 1.80; 95% CI: 1.14-2.84; p = 0.01) or ≥150 min/week (RRR = 1.64; 95% CI: 1.07-2.51; p = 0.02). Alcohol intake declined: 2% consumed >20 drinks/week at diagnosis; nearly none by 4–5 years (p < 0.001). Less than 20 drinks/week intake also dropped at 6 months and 1 year (p < 0.001). Smoking (4-7%) and spirituality (87-93%) showed no significant changes over time. Conclusion: Employment and income disruptions were most pronounced during early post-diagnosis, with only partial recovery observed over time. These findings highlight the need for survivorship plans that incorporate financial support and job reintegration opportunities to help YWBC regain occupational stability. Fertility preferences and attempts to conceive declined during follow-up, while relationship status remained largely stable. Encouragingly, physical activity improved during survivorship. Collectively, these results emphasize the importance of longitudinal support strategies that address the socioeconomic, social, and reproductive health needs of YWBC.

V. B. Sheppard¹, D. Chiranjeev², M. C. Edmonds¹, A. M. Kumar¹, L. L. Adams-Campbell²; ¹Department of Social and Behavioral Sciences, Virginia Commonwealth University, Richmond, VA, ²Office of Minority Health & Health Disparities Research, Georgetown University, Washington DC, DC.

Background: Weight changes during treatment and survivorship impact health outcomes in breast cancer survivors. These treatment-related changes include both substantial weight gain and loss. Many patients gain 5-15 lbs during treatment due to reduced physical activity, chemotherapy, hormonal therapy, and corticosteroids. Conversely, some experience weight loss related to treatment side effects or cancer cachexia.Our prior work suggests that women undergoing chemotherapy may shift their weight to a higher weight category during active treatment. Up to 70% of Black breast cancer patients have reported weight gain during survivorship. Weight gain increases cardiovascular risk, which is concerning given the elevated cardiac risk Black BCS face from therapies like doxorubicin and radiation. Heart disease is a leading cause of death among BCS and is most common in Black women. Emerging data also suggest that post-diagnosis weight gain may increase recurrence and lower survival, particularly in hormone receptor-positive cancers—types in which Black women experience the highest recurrence rates. Up to 50-70% of Black breast cancer survivors (BCS) experience weight changes during treatment and survivorship.Weight fluctuations may worsen insulin resistance and increase diabetes risk, which could affect cancer outcomes. Aromatase inhibitors can intensify these metabolic effects. Previous studies on weight change during treatment often lacked sufficient power to focus on Black women specifically, excluded cancer-related endpoints, or had limited data on lifestyle factors. This study aims to fill these gaps using detailed pre-diagnosis data and long-term follow-up of weight, lifestyle, and psychosocial factors in Black BCS. Methods: We examined 1,665 incident breast cancer cases (1995-2015) from the Black Women’s Health Study (BWHS), a nationwide prospective cohort of 59,000 Black women. Mortality and cancer details were obtained through medical record review. Post-treatment weight change was defined as the percentage difference between weight reported near diagnosis and at the 2-year follow-up. A change exceeding 10% from diagnosis weight was considered clinically significant. Survival analysis (Kaplan-Meier, Cox proportional hazards) was used to evaluate the relationship between weight change and all-cause mortality, controlling for age at diagnosis, education, stage, ER status, comorbidities, menopausal status, physical activity, and BMI. Women with metastatic disease at diagnosis were excluded.Results: Among 1,248 eligible women, 82% had no significant weight change (±10%) by 2 years post-diagnosis. Ten percent had significant weight gain (≥10%) and 8% experienced significant loss. There were 248 deaths during follow-up. Risk of death was higher among women with >10% weight change. Significant weight loss was associated with higher mortality (adjusted hazard ratio [HR]: 1.65; p=0.02), but weight gain was not (HR: 1.24; p=0.26). However, among women receiving both chemotherapy and hormone therapy, weight gain was linked to higher mortality (HR: 3.44; p=0.02).Conclusion:Nearly half of Black breast cancer survivors experience weight changes that start during treatment and continue afterward. Monitoring weight fluctuations is crucial in survivorship care to improve health and cancer outcomes. Weight loss may indicate more advanced disease, while weight gain could increase cardiometabolic risks. Including dietary data in future research might help better understand modifiable factors behind these patterns. The link between higher weight gain and increased mortality among women undergoing both chemotherapy and hormonal therapy highlights the need for comprehensive interventions for this group.

A. Allibhai, A. Allibhai; Student, Holy Trinity School, Richmond Hill, ON, CANADA.

Background: Breast cancer is a leading cause of cancer-related morbidity and mortality among women and is frequently associated with significant psychological distress, particularly around diagnosis, treatment, and survivorship transitions. Although up to 50% of patients experience clinically significant symptoms of anxiety or depression, mental health and emotional support services remain underutilized. This study aimed to evaluate the utilization of institutional psychosocial support services and identify factors associated with their use among breast cancer patients reporting moderate to severe psychological symptoms. Methods: We conducted a cross-sectional analysis using data from an electronic medical record-linked patient-reported outcomes registry at a single institution. Adult breast cancer patients who received care within the past year and reported moderate to severe psychological symptoms—defined as a score ≥4 on the Edmonton Symptom Assessment Scale (ESAS) for depression or anxiety—were included. Emotional support utilization was defined as having a documented referral to psychiatry, social work, or support groups. Patient demographic, clinical, and geographic factors were compared between users and non-users of psychosocial services using chi-square or two-proportion z-tests. Results: Among 340 eligible patients, only 118 (35.1%) utilized institutional emotional support services. Utilization was significantly higher among patients with greater symptom burden (ESAS 7-10: 63.3% vs. ESAS 4-6: 23.1%; p60 minutes (12.5%) (p<0.001). Trends toward higher utilization were observed among younger patients (<50 years: 41.3%) and those identifying as white (40.8%), although these differences did not reach statistical significance. No significant associations were found for gender or cancer stage. Conclusion: Despite strong evidence supporting the benefits of psychosocial interventions in breast cancer care, institutional support services remain underutilized, especially among patients with lower symptom burden or longer travel times. Accessibility and perceived need appear to be key drivers of engagement. Addressing geographic and systemic barriers, increasing provider referrals, and assessing pre-existing support systems may improve equitable access to mental health care for breast cancer patients.

N. Ganatra, A. Jamal, J. Doshi, P. Jain, S. Patel; Internal Medicine, Baptist Hospitals of Southeast Texas, Beaumont, TX.

Background:Delays in breast cancer treatment initiation are associated with worse outcomes, particularly among underserved populations. While socioeconomic disparities are well documented, there is no standardized tool to identify patients at high risk for treatment delays. We aimed to (1) develop a predictive model to stratify delay risk and (2) design a scalable quality improvement (QI) intervention targeting high-risk patients in a community oncology setting. Methods:We analyzed data from 609 breast cancer patients treated between 2018 and 2023 across a multi-hospital network in Southeast Texas. Treatment delays were defined using established modality-specific thresholds. Logistic regression identified predictors of delay, and a point-based risk score—the TIDE Score (Treatment Initiation Delay Estimator)—was developed using significant socioeconomic and clinical variables. Based on this score, we proposed a QI model incorporating early navigator engagement, social work referral, and expedited care pathways. Results:The final predictive model demonstrated good performance (AUC = 0.81). The TIDE Score ranged from 0 to 6 and included Medicaid insurance (2 points), unmarried status (1 point), age under 50 years (1 point), AJCC stage ≥ II (1 point), and absence of Medicare coverage (1 point). Patients scoring ≥4 had 3.6-fold increased odds of treatment delay (p < 0.001). Using this risk stratification, we designed a navigator-led QI intervention including EMR-based alerts at diagnosis, navigator contact within 5 days, and support service linkage within 2 weeks. This dual approach bridges risk prediction with timely intervention. Conclusion:The TIDE Score is a simple, SES-informed tool to identify breast cancer patients at risk of treatment delay. Coupled with a navigator-driven workflow, it offers a low-cost, scalable solution applicable across Texas and other underserved oncology settings.

R. C. Chidebe¹, S. Ipiankama¹, M. C. Onyedibe², I. I. Okoye³, S. Aruah⁴, O. Asogwa⁵, O. Ahmadu⁶, A. Adewumi⁷, L. Eriba⁸, D. Esiaka⁹, B. Olusegun¹⁰, M. Nandul¹¹, I. Zubairu¹², N. Mampak¹³, K. Omenukor¹⁴, D. Obi¹⁵, E. Ugwu¹, H. Dogo¹⁶, C. Okwuonu¹⁷, J. Chukwuorji¹⁸; ¹Patients Care and Research, Project PINK BLUE – Health & Psychological Trust Centre, Abuja, NIGERIA, ²Department of Psychology, University of Nigeria Nsukka, Enugu, NIGERIA, ³UNN Centre for Clinical Trials, University of Nigeria Teaching Hospital, Enugu, NIGERIA, ⁴Department of Radiotherapy and Oncology, National Hospital Abuja, FCT, NIGERIA, ⁵Medical Physics Department, Marcelle Ruth Cancer Centre, Lagos State, NIGERIA, ⁶Oncology Department, Federal Medical Centre, Abuja, NIGERIA, ⁷Oncology Department, NSIA-LUTH, Lagos, NIGERIA, ⁸Oncology and Radiotherapy Department, University of Benin Teaching Hospital, Edo State, NIGERIA, ⁹Center for Health Equity Transformation, University of Kentucky College of Medicine, Kentucky, KY, ¹⁰Oncology Department, University of Port-Harcourt Teaching Hospital, Rivers State, NIGERIA, ¹¹Oncology Department, Jos University Teaching Hospital, Plateau State, NIGERIA, ¹²Oncology Department, Ahmadu Bello University Teaching Hospital, Kaduna State, NIGERIA, ¹³Oncology Nursing, National Hospital Abuja School of Post-Basic Oncology Nursing, FCT, NIGERIA, ¹⁴Patients Care and Research, David Omenukor Foundation, Dallas, Texas, TX, ¹⁵Department of Community Medicine and Primary Healthcare, Nnamdi Azikiwe University Teaching Hospital, Anambra State, NIGERIA, ¹⁶Urological Surgery, University of Maiduguri Teaching Hospital, Maiduguri, NIGERIA, ¹⁷Family Care, Federal Medical Centre, Abia State, NIGERIA, ¹⁸Department of Psychology, University of Nigeria Nsukka, Enugu State, NIGERIA.

Background: Advanced breast cancer (ABC) affects patients’ psychological well-being and quality of life, with a higher prevalence of psychiatric disorders such as anxiety, depression, sleep disorders, and post-traumatic stress disorder. Despite evidence underscoring the importance of psychological support and psychotherapy in improving patients’ well-being, access to these services remains unknown in this population. This study examined access to psychological support and psychotherapy for patients with ABC in Nigeria. Methods: Of the (N=1,389) cancer patients recruited in the national study, (n=208) patients with ABC (203 females and five males; mean age = 50.53 years, SD = 11.36) were included in this study. Participants completed a questionnaire evaluating their access to psychological support. The data were analyzed using descriptive statistics in SPSS. Results: The findings showed that 75.5% of participants received their cancer diagnosis in a comforting and humane manner, while 53.8% were offered psychological counseling immediately after diagnosis. However, only 13.5% received counseling from a qualified clinical psychologist on the day of diagnosis. Cancer diagnosis had a significant psychological impact on 83.7% of participants, yet only 44.2% received psychological support during treatment, leaving 55.8% without access. Notably, 65.9% expressed a need for psychological support and psychotherapy during their treatment, and 78.8% indicated a willingness to utilize such services if available. Conclusions: The study reveals critical gaps in the availability and accessibility of psychological support and psychotherapy for patients with ABC. Establishing psycho-oncology clinics and recruiting clinical psychologists to provide psychotherapy for patients could help bridge this gap and enhance mental well-being.

G. Kirklin, A. Anderson, A. J. Kaler, M. Butaud, A. Singareeka, J. Harris, T. Jacobsen, B. Lim; Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Significance and Background: The diagnosis of advanced breast cancer (ABC) requires greater support and resource utilization compared to early-stage breast cancer. MD Anderson Cancer Center’s ABC Clinic is staffed with Advanced Practice Registered Nurses (APRNs) who provide personalized care through complex medical system, provide education about diagnosis/ treatment, assist with clinical trial process, explain genetic/genomic testing, discuss goals of care, and offer emotional support. In 2025, the ABC Clinic evaluated a new screening process for ABC patients seen in breast center to determine the fit for an ABC Clinic video visit, with the aim of increasing the number served. Purpose: To evaluate the impact of the screening process on access to the ABC Clinic by comparing the number and characteristics of patients served in 2025 versus 2024. Methods: Data were collected during visits between late March and June in 2024 and 2025. In 2024, patients were referred by a provider or self-referral. In 2025, ABC Clinic APRNs screened patients scheduled in breast oncology clinics. APRNs identified ABC patients who were Texas residents (due to licensing regulations), in active treatment, haven’t had a visit in the ABC Clinic in >365 days, and excluded patients who were going to hospice care. The oncology team would approve which patients to contact for an ABC Clinic video visit. Descriptive statistics were used for analysis. Findings: The new screening process increased provider referrals by 986% and patients with completed visits by 138% compared to 2024. In 2025, 188 unique patients were seen in 235 visits. Over half (54%) were new to the ABC Clinic, female (n= 186) with a diagnosis of ABC, and self-identified as White (68%) and non-Hispanic (79%). Most patients (86%) were diagnosed one to five years ago, married (62%), retired (32%), and had an ECOG status of 0 or 1 (89%). There were 56 total outgoing referrals to 15 different clinics or services with 30% of patients having at least one internal referral. Concerns identified by ABC patients: education (81%), coordination of care (46%), emotional concerns (42%), and physical concerns (40%). In 98% of visits, 40-60 minutes focused on care-related challenges. Patients seen in 2025 were more often be a new patient to the ABC Clinic (54% vs 22%), Hispanic (18% vs 12%), aged ≥ 70 years (20% vs 13%), have a ECOG score of 0 (34 vs 44%), and have a new ABC diagnosis (8% vs 6%). Patients seen in 2025 were more likely to present with knowledge deficit (81% vs 74%) and physical symptoms (40% vs 10%) compared to patients seen in 2024. Patients were more likely to discuss treatment related goals of care (38% vs 26%), have an internal referral (24% vs 20%), and the departments/services referred to more than doubled (15 vs 7) compared to referrals in 2024. Discussion and Implications: ABC patients presented with knowledge deficit and physical and emotional symptoms necessitating additional time at visits to assess and address concerns. An APRN-led visit allows for time to address education, physical symptoms, and goals of care. The screening process significantly increased referrals and new patients to the ABC Clinic and changed outgoing referral patterns and increased number of new patients. Future efforts will focus on outcomes for first time patients and long-term impact of the screening implementation.

R. Thomas¹, C. Richardson², C. Smith³, J. R. Benson²; ¹School of Clinical Medicine, University of Cambridge, Cambridge, UNITED KINGDOM, ²Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge, UNITED KINGDOM, ³Patient Experience Team, Addenbrooke’s Hospital, Cambridge, UNITED KINGDOM.

Background: The Holistic Health Follow Up Breast Cancer Clinic provides a consultation service for early stage breast cancer patients that is available towards the end of their treatment pathway when all modalities of therapy have been completed. These clinics are run by specialist breast care nurses and assess a patient’s knowledge and understanding of treatments to-date. A plan for subsequent follow up and support is proposed and coordinated that aligns with current research suggesting the importance of a broad and multifaceted approach that encompasses various health domains including physical, emotional and social needs after treatment. Methods: A service evaluation audit was conducted to gauge the effectiveness of the holistic clinic in supporting patient knowledge and confidence in three key areas: self-examination, planning of follow up imaging and knowledge of treatments received and potential adverse effects that might impact on quality-of-life. Patients were further probed in terms of understanding different types of treatment and why these were recommended. A questionnaire was designed to assess the aforementioned areas using a combination of ordinal rating scales and free-text responses. Patients were allowed two weeks for completion and return of the questionnaire without any reminders being issued. Results were analyzed with graphic representation of numerical data and assessment of patient confidence in each designated area. Additional themes were extracted from the free-text responses to identify strengths and limitations of the holistic clinic assessment, thereby offering insight into further development of the service and improving patient care. Results: The questionnaire was issued to 206 patients with a response rate of 30% (61/206). More than 80% of patients reported improved understanding of follow up imaging whilst over 90% of patients considered their understanding of treatment and side-effects to be improved following a holistic consultation. By contrast, only 57% of responders either fully or partly declared any improved confidence in performing self-examination. Amongst the various treatment modalities, the proportion of patients who fully understood reasons for receiving surgery, radiotherapy and chemotherapy were 98%, 79% and 64% respectively. Moreover, only half (50%) understood the rationale for extended hormonal therapy and fewer than half (41%) fully appreciated the adverse impact of ovarian suppression. Free-text responses revealed some uncertainty about the exact purpose of the holistic clinic with requests for more emphasis on practical support in areas such as mental health and lymphedema and tailoring of support literature based on personal need. Conclusion: The holistic clinic achieves its overall aims with more than three-quarters of patients reporting improved understanding of treatments received, treatment-related side-effects and follow up imaging strategies. Areas that were less well addressed included hormonal therapies and breast self-examination where more thorough explanation, adjustments of information provision and better signposting of support services may be indicated.

K. E. Dibble¹, J. Stal¹, S. M. Rosenberg², C. Snow¹, A. H. Partridge¹; ¹Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, ²Population Health Sciences, Weill Cornell Medicine, New York, NY.

Background. Young women living with metastatic breast cancer (MBC) experience many physical and psychosocial difficulties heightened by a disrupted life trajectory and the burden of ongoing treatment. We conducted a focused evaluation of how survivors with MBC alleviate their symptoms/treatment-related side effects and survivorship concerns. Methods. Women diagnosed with MBC (18-39 years) participating in an ongoing prospective intervention study (Young, Empowered and Strong; NCT04379414) at Dana-Farber Cancer Institute were invited to participate in a semi-structured virtual interview. Descriptive statistics were used to describe the sample and quantify frequency of side effects, concerns, alleviation techniques, and perceived efficacy. We conducted a thematic analysis to further explore these topics. Results. The convenience sample comprised 20 women with a median age of 40 years at enrollment (SD=3.84, range: 30-46) and 34 years at MBC diagnosis (SD=3.03, range: 28-38). At time of interview, median time from initial breast cancer to MBC diagnosis was 2.14 years (SD=2.56, range: 0-9.51). Most were non-Hispanic (85%), white (80%); half had a graduate degree (50%). Symptoms/side effects: Overall, all women reported experiencing disease symptoms/treatment-related side effects. Fatigue (50%), gastrointestinal issues (35%), menopausal symptoms (25%), and nausea (25%) were most frequently reported. Of the 19 women who reported efforts to alleviate symptoms/side effects of MBC and its treatment, 18 (94.7%) tried more than two methods, and 7 (38.8%) tried more than four methods, including prescription medication, exercise, diet/hydration, over-the-counter medication, sleep, acupuncture/massage, and medical marijuana. Of these, participants reported utilizing several methods to alleviate symptoms/side effects in tandem with other methods. Concerns: All but one participant reported survivorship concerns including fear of disease progression (68.4%), mental health (52.6%), financial toxicity (36.8%), future of family/children (36.8%), feeling trapped (15.8%), fertility/childbearing (15.8%), and sexual health (15.8%). The most common methods to alleviate concerns were social support networks (53.3%), talk therapy (46.7%), staying busy (33.3%), and exercise (26.7%). Of the 15 women who tried more than one method to alleviate their concerns, all tried more than two methods and 10 more than four methods. Of these, most reported utilizing multiple methods because previous methods had not worked for them or updated treatments introduced new side effects. Conclusion. Young women with MBC have a high burden of symptoms/side effects and concerns and utilize numerous strategies to alleviate them. Multiple approaches were often employed, both because symptoms/side effects and concerns changed with new treatments and because methods were ineffective. Supporting women to streamline these efforts may address symptoms/side effects and concerns and may help to manage disease expectations and optimize overall well-being during MBC survivorship.

D. Remen, International Health Strategies; Strategic Initiatives, Ellie Fund, Needham, MA.

BackgroundÏEllie Fund provides essential support services for breast cancer patients to ease the stresses of everyday life, allowing the focus to be on family, recovery, and healing.ÏIn 2019, Ellie Fund launched an Outcomes Measurement Program to empirically measure the impact of its non-medical services on patients’ physical, emotional, and financial health and show improved quality of life (QOL) during treatment.ÏThis research is an essential continuation of the study conducted in 2024 and presented at SABCS, incorporating a broader dataset and deeper analysis of demographics (e.g., race, income), and examining how these factors correlate with stress reduction after receiving Ellie Fund services.ÏLonger term, this research aims to link support services to improved breast cancer outcomes. MethodsÏEach patient participant selected two services, such as grocery gift cards, delivered meals, transportation to medical appointments, childcare reimbursement, housekeeping and integrative therapies. Services were provided monthly for 3 months for non-metastatic patients (Stages 0-3) and 6 months for metastatic patients (Stage 4).ÏData were collected via voluntary surveys administered before and after service delivery, using the Perceived Stress Scale (PSS-14) which includes 14 standard questions scored numerically. Twelve additional questions assessed QOL changes using a 4-point Likert scale.ÏThis analysis focused on surveys from patients who started services 2019-2025 and completed both surveys. The McNemar test was used to measure the association between pre- and post-service stress improvements (primary outcome) and evaluate disease type in relation to perceived stress (secondary outcome). A Cochran-Mantel-Haenszel test was used to measure the association between stress and race, controlling for income (secondary outcome).ResultsA total of 1,047 patients enrolled in the program and completed at least one survey. As participation in survey items was not mandatory, sample sizes varied by question. Analyses were conducted only on cases with both pre- and post-survey responses.Primary outcomes highlighted the relationship between service use and patient-reported outcomes:ÏA statistically significant reduction in the proportion of participants reporting high perceived stress following receipt of Ellie Fund services (p < 0.05).ÏStatistically significant decreases were seen in emotional, physical, financial, and daily life stress levels (p < 0.05).ÏStatistically significant QOL improvements were reported in 6 key domains, namely (1) maintaining order in the home, (2) managing treatment side effects, (3) physical self-care, (4) food access, (5) focus on family, and (6) medication access.For secondary outcomes, among non-White patients, higher income is associated with 3.4x higher odds of stress reduction compared to lower income (statistically significant). For White patients, the association is weak (not statistically significant). Both patients with and without metastatic disease experienced significant improvements in their perceived stress pre- and post-services (p<0.05). In the non-metastatic group, stress was reduced about 67%, slightly higher compared with the metastatic group (60%). ConclusionEllie Fund’s services are associated with meaningful reductions in stress and improvements in various aspects of QOL among breast cancer patients, especially for higher-income non-White patients. Data suggest that below a certain income, more robust interventions may be needed. These findings underscore the value of supportive care to complement medical cancer treatment and also suggest a vital role for non-medical services in preventative breast care, and to shorten the time between diagnosis and initiating treatment. Further research is warranted to better understand the forces driving QOL improvements.

H. S. Rugo¹, M. Chase², M. Rutt³, M. Smith⁴, S. Weldon⁵, E. Pain⁶, G. Vadnerkar⁷, T. Sen⁸, S. Padhi⁸, N. Nadimpalli⁸, L. Santarsiero⁷, C. Auld⁹, N. Harbeck¹⁰, A. B. Chagpar¹¹; ¹Duarte Cancer Center, City of Hope Medical Centre, Duarte, CA, ²n/a, Life on the Cancer Train, Atlanta, GA, ³n/a, Living Beyond Breast Cancer, Philadelphia, PA, ⁴n/a, Research Advocacy Network, Plano, TX, ⁵n/a, Unite for HER, Malvern, PA, ⁶Online Patient Community, Carenity, Paris, FRANCE, ⁷n/a, Novartis Pharmaceuticals Corporation, East Hanover, NJ, ⁸n/a, Novartis Healthcare Ltd, Hyderabad, INDIA, ⁹US Medical Affairs, Novartis Pharmaceuticals Corporation, East Hanover, NJ, ¹⁰Department of Obstetrics and Gynecology, LMU University Hospital, Breast Center, Munich, GERMANY, ¹¹Department of Surgery, Yale University School of Medicine, New Haven, CT.

Background: While most new HR+/HER2− BC cases are diagnosed (dx) as early BC (EBC), recurrences are an urgent concern as approximately 50% of recurrences occur in ≤5 years despite standard-of-care endocrine therapy and this risk can persist for decades after dx. Little has been published on the awareness and understanding of BC ROR from the pt and caregiver perspective and how this may influence shared decision-making and quality of life (QoL). Here, we present the results of an online survey of pts and subsequent social media analysis (SMA) of pts and caregivers including important insights on ROR. Methods: Female pts from France, Germany, Italy, the UK, and the US were invited to participate in a survey developed with input from medical experts and pt advocates on the Carenity platform, an online pt community, between Dec 1, 2021 and Jan 24, 2022; results from the US are presented. Additionally, deidentified data from publicly available posts by US pts and caregivers on social media sites, forums, and blogs between Apr 1, 2023 and Mar 31, 2025 were analyzed using the Sprinklr social media aggregator. Results: Of 220 US pts who responded to the Carenity survey, 57 (26%) reported being dx with HR+/HER2− BC, 39% with HER2+, and 22% with triple negative BC (TNBC). Among pts with HR+/HER2− BC, 38 pts (67%) were initially dx with EBC (stage I-III); of those, 11 pts (29%) recurred as metastatic BC (MBC). In the SMA, a screen of 3440 posts found 1622 relevant to EBC and ROR; 82% of conversations were driven by pts. In the Carenity survey, many pts initially dx with HR+/HER2− EBC wished they had received more relevant information on chances/duration of survival (32%) or emotional support options (26%) from their healthcare provider (HCP) at the time of dx, some of whom indicated they received no information at dx (chances/duration of survival: 22%; emotional support options: 67%). Many pts who reflected back on initial dx and wanted but had not received information on chances/duration of survival (75%) or emotional support options (40%) experienced a metastatic recurrence. This was reinforced by the SMA which identified recurrence rate and peer support as topics pts were seeking more information on. Posts related to ROR highlight pt and caregiver concerns about late recurrences, limited long-term monitoring, and persistent worries about unexpected recurrences. Pts also expressed feelings of being overwhelmed by the fear of BC recurrence. Within the Carenity survey, limiting risk of cancer metastasis and living as long as possible ranked high among treatment (tx) expectations. Similar themes emerged from the SMA, in which ROR was identified as one of the top aspects leading to positive perceptions of available tx. Surveyed pts with HR+/HER2− BC felt they had less access to services and support programs compared to pts with HER2+ or TNBC. In the SMA, pts discussed challenges and stressors associated with the lack of ROR knowledge within their support systems. Conclusions: Pts prioritize reducing ROR when ranking their tx options yet lack sufficient information and understanding about ROR. This is especially important for those with HR+/HER2− EBC whose risk includes early and late recurrence, a majority of which are metastatic recurrences. Conversations between HCPs and pts can be complex, further complicated by the number of HCPs communicating ROR to a single pt, varying degrees of pt health literacy, and impact to pt QoL. These analyses shed light on the need for greater knowledge and education about ROR, while also ensuring pts are offered support services to help address the impact of ROR on QoL for both pts and loved ones, from initial dx, throughout tx, and beyond.

S. Hirani¹, R. A. Vierkant², N. L. Larson³, S. D. D’Andre⁴, F. J. Couch⁵, J. E. Olson³, K. J. Ruddy⁴; ¹Department of Hematology Oncology, Mayo Clinic Health System, Eau Claire, WI, ²Division of Clinical Trials and Biostatistics, Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, ³Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, ⁴Department of Medical Oncology, Mayo Clinic, Rochester, MN, ⁵Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.

Background: Smoking, a known risk factor for numerous cancers, negatively impacts long-term survival in breast cancer (BC) survivors (Parada H Jr et al., 2017; Pierce et al., 2019). This study aims to characterize baseline smoking behaviors among breast cancer patients who self-reported smoking during an initial survey. Objectives: To assess attributes of patients self-reporting as current smokers near BC diagnosis, examining demographics, habits, quality of life, cancer treatments, comorbidities, and finances. Methods: Patients with newly diagnosed BC seen at Mayo Clinic Rochester between 2014-2024 were invited to enroll in the Mayo Clinic Breast Disease Registry. Consenting participants who completed self-reported questionnaires at baseline were included in this study. Smoking status and related variables at the time of survey completion were assessed via a baseline questionnaire, classifying participants as current, former, or never smokers. Of 3,959 participants completing baseline surveys, 3,729 were analyzed after excluding 103 with missing smoking data and 127 with their baseline survey returned >1-year post-diagnosis. Categorical variables were summarized with frequencies and percents, continuous variables with distributional statistics. Univariable associations with current smoking were assessed via two-sample t-tests (continuous) and chi-square or Fisher exact tests (categorical). Significant variables (p<0.05) were included in a multivariable logistic regression model. Results: Among 3,729 BC patients (mean age 58.3 years, SD 12.9), 99.1% were female, 97.1% White, and 98.7% non-Hispanic. Only 2.7% reported financial difficulty, 56.4% had a bachelor’s degree or higher, 81.7% were married or equivalent, and 21.7% consumed ≥5 alcoholic drinks/week. Tumor stage distribution was as follows: Stage 0 (13.9%), Stage 1 (43.9%), Stage 2 (28.9%), Stage 3 (8.9%), and Stage 4 (4.5%); 33.8% received chemotherapy, 56.5% radiotherapy, 63.6% endocrine therapy, and 42.2% underwent mastectomy. Current smokers (2.6%, n=95) had a median diagnosis age of 59.1 (IQR 31.8-87.1),with 32.6% consuming ≥5 drinks/week (vs. 21.5% in non-smokers, univariable p=0.012), 69.5% with less than a Bachelor’s degree (vs. 42.9%, p<0.001), 9.6% facing financial difficulty (vs. 2.5%, p<0.001), and 10.5% diagnosed within 270-365 days after survey return (vs. 4.2%, p=0.022). Tumor stage showed 47% with Stage 1 (vs. 43.7%, p=0.245); 33.7% received chemotherapy, 60.0% radiotherapy, and 58.9% endocrine therapy. Current smokers had a mean smoking initiation age of 19.9 (SD 6.2), smoked 12.5 cigarettes/day (SD 7.9) for 32.8 years (SD 14.1), with mean 22.3 pack-years (SD 17.2).Univariable associations of demographic and clinical characteristics with current smoking showed Compared to never or former smokers, current smokers at the time of survey took a longer time to return their baseline survey (p=0.022), were more likely to consume five or more alcoholic drinks per week (p=0.012), were more likely to have difficulty paying their bills (p<0.001) and were less likely to obtain a Bachelor’s degree or higher (p<0.001). These associations remained significant after multivariable adjustment. Conclusion: Current smoking (2.6%) soon after a BC diagnosis was independently associated with delayed survey return, higher alcohol use, financial difficulty, and lower education. Assessing smoking status and referring patients to smoking cessation programs are critical for addressing these risk factors and improving health outcomes. These findings highlight distinct socioeconomic and behavioral profiles among current smokers, suggesting potential targets for tailored interventions.

N. Camejo¹, C. Castillo¹, R. Servetto¹, G. Muñoz¹, J. Manzanares¹, D. Amarillo¹, M. Guerrina¹, G. Herrera², C. Dörner³, G. Krygier¹; ¹Clinical Oncology, Hospital de Clinicas, Montevideo, URUGUAY, ²Department of Preventive and Social Medicine, School of Medicine, Montevideo, URUGUAY, ³Clinical Oncology, Hospital Departamental de Soriano “Zoilo A. Chelle”, Soriano, URUGUAY.

Introduction: Sexual dysfunction is a prevalent issue among breast cancer survivors and may have a particular impact on younger women, for whom long-term quality of life is crucial.Objectives: To explore the prevalence and predictors of sexual dysfunction in breast cancer survivors under 50 years old in Uruguay, and to assess the influence of different treatment modalities on their Female Sexual Function Index (FSFI) scores.Methods: This subgroup analysis included patients younger than 50 years from a multicenter observational ambispective study. Eligible women had completed treatment for stage I to III breast cancer (surgery, chemotherapy, and radiotherapy) at least 12 months prior. Sexual dysfunction was defined as FSFI less than or equal to 26.55. Logistic regression models were used to identify associations between treatment modalities and dysfunction.Results: Of the total cohort, 41 patients were under 50. In this group, 65.9 percent had FSFI scores indicating dysfunction. Mastectomy was associated with lower FSFI scores across all domains compared to breast-conserving surgery. The use of gonadotropin-releasing hormone agonists was significantly associated with higher odds of dysfunction (odds ratio 5.7, 95 percent confidence interval: 1.5 to 25.6). Chemotherapy showed no significant detrimental effect in this subgroup.Conclusions: Sexual dysfunction is highly prevalent among young breast cancer survivors in Uruguay and appears to be influenced by specific treatments. These findings support integrating sexual health counseling and fertility-preserving strategies into early survivorship care for this population.

S. Weldon¹, V. Worthy², R. Fairley², E. Powers², G. Kelly¹, J. Meakim¹, E. Fortune³; ¹Non Profit Organization, Unite for HER, Malvern, PA, ²Non Profit Organization, TOUCH, The Black Breast Cancer Alliance, Annapolis, MD, ³Research, Cancer Support Community, Washington, DC.

Background: Care for HER is a campaign that serves Black breast cancer patients nationwide with free access to: 1) integrative care therapies and services, and 2) 24/7 culturally tailored patient navigation by Black nurses and social workers who are also breast cancer survivors. This study aims to evaluate program outcomes and satisfaction, as reported by program participants. Method: After participating in the Care for HER program, participants provided feedback online for multiple program evaluation metrics using a combination of scaled response questions: satisfaction and resource use (5-point scales), perceived benefits (4-point agreement scale and yes/no items), pre- and post-program distress (0-10 scale), and likelihood of recommending to others (0-10 scale). Descriptive and bivariate results are presented.Results: Between April and May 2025, 57 Black women completed the survey, with an average age of 52 (SD=9.1; range 33-71) and average time since diagnosis of 14 months (SD=11.6; range 6-71 months). Results show 98% report being satisfied or very satisfied with the wellness passport program of integrative care therapies and services, with the average likelihood of recommending to others a 9.4 out of 10; 93% of program participants report using resources provided (47% often or very often and 46% sometimes), and 7% rarely or never. As a result of the program, participants reported being better able to find support to reduce treatment side effects (75%) and reducing at least one aspect of financial strain (83%). Nearly all participants reported improvements in their health behaviors, with 95% saying they felt more motivated to make healthier food choices and 93% indicating a better understanding of the benefits of physical activity. Many also experienced gains in navigating the healthcare system and advocating for themselves: 89% reported a better understanding of the resources and services available to them, 88% felt better equipped to follow their treatment plan, and 84% felt more confident advocating for themselves in healthcare settings. Additionally, 69% of participants agreed or strongly agreed that they were better able to understand their diagnosis and treatment options. Average distress score dropped from 6.6 before the program to 2.7 after, reflecting a 3.9-point decrease. Overall, 85% of participants reported reduced distress, 11% saw no change, and 4% reported an increase. High distress (scores of 8-10) declined from 39% to 0%, while those reporting no distress (score of 0) rose from 5% to 21%. Frequency of resource use was significantly associated with reduction in distress (F=4.252, p<.02), such that those who reported using available resources often or very often had the largest reduction in distress after program participation (M=-3.8), compared to those who only use resources sometimes (M=-3.0). Additionally, more frequent use was significantly correlated with satisfaction (r=.43, p<.001).Conclusions: Participation in the Care for HER program was associated with improvements in health behaviors, managing side effects, healthcare navigation, and understanding of diagnosis and treatment, as well as a notable reduction in distress, suggesting the program effectively supports practical and emotional well-being for women with breast cancer. Further, program satisfaction and perceived benefits were significantly correlated with frequency of resource use, indicating that greater engagement enhances program outcomes. Programs like Care for HER provide essential supportive services and empower patients to take a more active role in their cancer care. Expanding access is crucial, as patients—especially those from historically underserved communities—cannot obtain these services through traditional healthcare systems.

J. Fukui¹, L. Imai¹, C. Shen¹, K. Baron¹, M. Toyama¹, I. Pagano¹, A. Oamil¹, H. Kumagai², J. Wan², P. Cohen², P. Yamada³, C. Teranishi-Hashimoto⁴; ¹Cancer Biology, University of Hawaii Cancer Center, Honolulu, HI, ²Leonard Davis School of Gerontology, University of Southern California, Los Angeles, CA, ³Kinesiology and Rehabilitation Science, University of Hawaii at Manoa, Honolulu, HI, ⁴Women’s Health and Cancer Rehabilitation, Rehabilitation Hospital of the Pacific, Honolulu, HI.

Abstract: Correlations Between MOTS-c, Body Fat, and Muscle Strength in a Diverse Ethnic Cohort of Breast Cancer Survivors in Hawai’i Background:Mitochondria Open Reading Frame within the Twelve S rRNA c (MOTS-c) is known to respond to exercise, influencing metabolic, cardiovascular, and muscular systems. However, the connection between MOTS-c and markers of health and fitness in Asian cancer survivors is underexplored. Our study aimed to examine the impact of a 12-week concurrent exercise program on MOTS-c levels in Asian breast cancer survivors and determine if anthropometric and fitness-related factors correlate with pre- and post-exercise MOTS-c levels.Methods:Twenty-five breast cancer survivors participated in a 12-week concurrent exercise program. Metrics were assessed before and after the exercise program, including visceral/subcutaneous fat mass, volume, bone mass density (BMD), bone mineral content (BMC), body fat percentage, 1-repetition maximum (1-RM) strength, isokinetic peak torque and maximum work, as well as cardiorespiratory (VO2 peak) and muscular endurance. Plasma MOTS-c was measured using an in-house enzyme-linked immunosorbent assay. Statistical analyses, including t-tests and correlation analyses, were conducted.Results:There was a significant 8.3±13.0% increase in MOTS-c levels following exercise (pre: 254.6±39.9 pg/ml, post: 272.5±36.0 pg/ml, p=0.015). Based on varying responses, the participants were divided into two groups: low responders (n=11) and high responders (n=14). Eight low responders showed a decrease in MOTS-c after exercise, while high responders showed an 18% increase. Pre-exercise MOTS-c levels were positively correlated with baseline body mass, body fat percentage, muscular strength, isokinetic maximum work/torque, and changes in BMD and BMC (p0.05). When analyzed separately for low and high responders, these significant correlations were only present in the high responder group. Additionally, MOTS-c showed a weak negative correlation with muscular endurance as measured by the chair squat test, but for the high responders, a significant negative relationship was found between MOTS-c and core endurance, assessed by plank hold performance (p=0.0145).Summary:Our study showed significant improvement in MOTS-c levels following our exercise program, with high responders showing significant correlations between MOTS-c and body fat, skeletal muscular strength, and BMD and BMC. This exemplified that MOTS-c is associated with bone and metabolic health. Since MOTS-c is correlated with strength but not endurance, strength training should be emphasized in exercise programs aimed at improving cancer survivorship outcomes.

Z. Wasim, N. Goyal, A. Konstantis, S. Patel; Oncology, Princess Alexandra Hospital, Harlow, UNITED KINGDOM.

Background: Lifestyle interventions are known to impact physical activity, mental wellbeing, and cancer recovery outcomes. This project evaluated the effectiveness of a lifestyle medicine coaching program over 12 weeks for overweight and obese breast cancer survivors on follow up across three domains: physical activity (Exercise Vital Sign – EVS), mental wellbeing (Warwick-Edinburgh Mental Wellbeing Scale – WEMWBS), and cancer wellbeing (FACT-G7 scores). Methods: Fifteen participants were assessed pre- and post lifestyle medicine program of education and patient led goal-based coaching for healthy behaviour change led by a lifestyle medicine physician, nutritionist, cancer exercise specialist and yoga teacher. Exercise minutes per week, mental wellbeing scores, and cancer wellbeing scores were collected and analysed using paired t-tests and Wilcoxon Signed-Rank Tests. Results: Significant improvements were observed across all three outcome areas. Weekly exercise minutes increased from a mean of 75.2 to 201.0 (t (14) = -5.81, p < .001, Cohen’s d = 1.5). Mental wellbeing scores improved from a mean of 45.0 to 53.0 (p < .05), with 86% of participants showing a meaningful positive change. Cancer-related wellbeing scores improved from 14.3 to 20.5 (t (14) = -3.266, p = .006). The proportion of participants with low mental wellbeing reduced from 43% to 11% post-intervention, while those reporting high wellbeing increased from 7% to 16%. Conclusion: The lifestyle coaching program produced statistically significant and clinically meaningful improvements in physical activity, mental wellbeing, and cancer-related health outcomes. These findings support the integration of holistic, behaviour-based coaching interventions into health promotion and cancer survivorship care pathways.

M. S. Montemor¹, S. S. Santos², B. M. Figueroa², K. G. Sousa², F. B. Makdissi², S. M. Sanches²; ¹Departamento de Obstetrícia e Ginecologia, Hospital das Clínicas da Faculdade de Medicina da USP, São Paulo, BRAZIL, ²Centro de Referência de Tumores de Mama, AC Camargo Cancer Center, São Paulo, BRAZIL.

Introduction: Breast cancer (BC) is a major burden, affecting many working age women. In Brazil, it is estimated an adjusted incidence rate of 41.9 new cases in 100 000 women per year, of these, around 40.0% are diagnosed in advanced stages (stages III and IV). An important fraction of recently diagnosed BC patients will undergo neoadjuvant or adjuvant chemotherapy (CT). The treatment impact in work and household routine is an important factor to be discussed by healthcare team and patients in each therapeutical plan. Objective: Evaluate working status of recently diagnosed BC patients and CT implications on social and economic stability. Methods: We conducted a prospective observational study among insurance-assured patients diagnosed with BC in a Brazilian Cancer Center with indication of neoadjuvant or adjuvant CT. Patients were evaluated with a self-related questionnaire at diagnosis and after CT finished. Results: 44 female patients diagnosed with BC from March to November of 2024 responded to the questionnaire. Median age of diagnosis was 50 years old, 61.4% of patients self-recognized as white, 72.7% were married, 27.3% had no children. About 11.4% patients were in use of antidepressants and 25.0% at psychological care prior to diagnosis. Clinical stages II (54.5%) and III (25.0%) were most prevalent, and all patients were non metastatic. Luminal subtype totalized 77.3% and triple negative 6.8%. Around 52.3% patients underwent neoadjuvant CT.Nearly 29.5% and 57.0% of patients had total or partial participation in family income, respectively. Additionally, 31.8% patients had no financial dependents. Patients worked 36.5 hours per week in average , and 70.5% were socially secured. The median satisfaction rate with work was 8.0/10.0. Almost 41.0% intended to maintain full time job, 31.8% planned to keep it partially and 27.3% desired to halt it during treatment. Approximately 43.2% of women didn’t follow the original labor plan during treatment: of these, 14/19 worked less than expected and 5/19 increased workload. The majority of patients (65.9%) kept fully or partial working, and all of them described adjustments to do so. Most common adaptations were home-office regimens and reduced working hours. Most of bosses were women (79.5%) and 60.0% were described as empathic to patient’s situation. Degree of work satisfaction was maintained after CT. The majority of the group (65.9%) didn’t experience income decrease during treatment.Finally, 59.0% of patients felt depressed or psychological altered during treatment and 47.7%received psychological support. Discussion: The group analyzed comprises mostly socially secured and economically active women, with decent social-family support. Most of the group managed to keep working and didn’t have income decrease during treatment. It is essential to notice that all of them needed to adjust to keep working. Therefore, flexibility and leadership empathy are key to secure working status for breast cancer patients. Conclusion: It is of utmost importance to approach working status and expectations with recently diagnosed breast cancer patients, as this population consists mostly of economically active people. Maintaining and returning to work enable women to be socially integrated. Moreover, returning to work has been shown to be associated with higher survival rates.

A. Antai¹, K. Crew², P. Kakani³; ¹Epidemiology, Columbia University, Midland, MI, ²Oncology/ Epidemiology, NewYork-Presbyterian/Columbia University Medical Center, New York, NY, ³Internal Medicine, NewYork-Presbyterian/Columbia University Medical Center, New York, NY.

Authors: Angelica Antai, Preeti Kakani, Katherine D. CrewCharacter count including title (no spaces): 2479Character limit including title (no spaces): 3400 Factors Associated with Adherence to Surveillance Mammography Among a Racially and Ethnically Diverse Cohort of Breast Cancer SurvivorsBackground: Annual mammography is a recommended component of post-treatment surveillance for breast cancer survivors and is associated with earlier detection of local recurrence and contralateral breast cancer. However, adherence to surveillance remains variable. Psychological distress, including depression and anxiety, has been proposed as a potential barrier. We investigated demographic, clinical, and mental health factors associated with adherence to surveillance mammography in a diverse cohort of breast cancer survivors.Methods: We conducted a retrospective cohort study of women diagnosed with stage 0-III breast cancer between 2018 and 2023 at Columbia University Irving Medical Center in New York, NY. We excluded women with stage IV disease, bilateral mastectomies, or less than 15 months of follow-up after breast cancer diagnosis. The primary outcome was receipt of at least one mammogram within 15 months of diagnosis. Psychological distress was defined using ICD-10 codes for depression and/or anxiety. Sociodemographic and clinical variables were extracted from the electronic medical record and tumor registry, including age at diagnosis, race and ethnicity, marital status, primary health insurance type, cancer stage, local and systemic treatments. Multivariable logistic regression was used to identify factors associated with adherence to surveillance mammography.Results: Among 1,970 eligible patients, the mean age was 59.2 years (SD, 11.9). The cohort included 33% Hispanic, 32% non-Hispanic White, 12% Black, and 5% Asian women. Overall, 94.6% (n=1,863) were adherent to surveillance mammography guidelines. On multivariable analysis, psychological distress was not significantly associated with adherence to surveillance mammography (odds ratio [OR]=0.89; 95% confidence interval [CI]=0.57-1.39). Compared to non-Hispanic White women, Hispanic ethnicity was associated with increased adherence (OR=1.95; 95% CI=1.15-3.28). Meanwhile, being married (OR=0.63; 95% CI=0.41-0.95) was associated with decreased adherence compared to being unmarried.Conclusions: In this large, racially and ethnically diverse urban breast cancer cohort, adherence to mammography surveillance was high. Psychological distress was not independently associated with non-adherence, suggesting that institutional supports may reduce its potential impact. Interestingly, Hispanic women had nearly 2-fold higher mammography adherence compared to their White counterparts, which may represent cultural differences or disparities in breast cancer worry or fear of recurrence. These findings highlight the importance of tailored survivorship care strategies to promote equitable adherence among breast cancer survivors.

R. Tran¹, Y. Liu², C. Huang³, K. Chang³, F. Hsiao², T. Fung⁴, C. Lo³, W. Kuo³, G. Sander¹, R. J. Wong¹, K. N. Hitesman¹, M. Thomas¹, J. Chen¹, S. Jeong¹, M. Tan¹, J. H. Wang¹; ¹Cancer Control and Prevention Program, Lombardi Comprehensive Cancer Center, Washington, DC, ²School of Nursing, National Taiwan University, Taipei City, TAIWAN, ³Department of Surgery, National Taiwan University Hospital, Taipei City, TAIWAN, ⁴Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston, MA.

Background and Objective: Breast cancer (BC) patients undergoing curative treatment commonly experience appetite loss and subsequent poor dietary quality. The role of nutrition in symptom burden and functioning during treatment remains inadequately studied among BC patients. This study examined these associations among breast cancer patients and whether the associations varied across different cultural dietary practices. Methods and Analysis: Cross-sectional data from 81 American (non-Hispanic White, Black, Hispanic) and 81 Taiwanese female BC patients receiving primary treatment (e.g., surgery, chemotherapy, and/or radiation) were collected. Participants were diagnosed between 2021 and 2024 with stage 0-III primary BC and enrolled within six months of diagnosis. Dietary intake was assessed using an automated 24-hour recall tool (ASA24) on three randomly selected days. Diet quality was assessed by the Healthy Eating Index (HEI-2020) through four categories: ‘good’ (80-100), ‘needs improvement’ (70-79), ‘poor’ (60-69), or ‘very poor’ (0-59). A good quality diet refers to an adequate intake of healthy foods (e.g., fruits, vegetables, whole grains, dairy, protein foods, and fatty acids), and a limited intake of undesirable dietary components (e.g., refined grains, sodium, added sugars, and saturated fat). Poor-quality diets suggest an insufficient intake of healthy foods and an excess intake of undesirable components. Patient-reported symptoms (e.g., insomnia, fatigue, appetite loss, and diarrhea) and functional outcomes (e.g., physical, emotional, social, and role functioning) were measured via EORTC QLQ-BR30. Linear regression examined the associations of HEI and subcomponent scores with each study outcome, adjusting for nationality, age, cancer stage, treatment type, body mass index, calorie intake, physical activity, and financial difficulties. Appetite loss was included in all regression models as a confounder, except when it was a symptom outcome. Results: Only 11% of the sample (Americans: 7%, Taiwanese: 4%) had good diet quality. Over 68% had poor diet quality. A higher percentage of Americans (25%) than Taiwanese (13%) had very poor diets. Americans had higher intakes of added sugar and saturated fat, while Taiwanese had higher intakes of sodium (p < 0.001). However, nationality was not a predictor of the outcomes. The overall HEI scores were not associated with any study outcomes. Patients with more severe appetite loss reported higher total fruit intake (β = 3.21, 95% CI: 0.32, 6.09). Total vegetable intake was inversely associated with insomnia (β = -5.12, 95% CI: -10.1, -0.13). Higher seafood and plant protein intake was associated with a higher prevalence of diarrhea (β = 3.44, 95% CI: 0.37, 6.51), and higher saturated fat intake was associated with poorer physical functioning (β = -1.11, 95% CI: -2.16, -0.07). Conclusion: Most patients undergoing BC treatment had poor diet quality. These cross-sectional findings do not establish causation; however, we noted certain dietary characteristics with specific symptoms. Longitudinal investigations in a larger sample will be needed to further evaluate these observed associations to inform dietary recommendations for BC patients during treatment.

J. Hundal¹, S. Peshin², F. Bashir³, H. Bazroodi⁴, E. Takrori⁵, M. Kurian⁶; ¹Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, ²Internal Medicine, Norton Community Hospital, Norton, VA, ³Medical Sciences, Shiraz University of Medical Sciences, Shiraz, IRAN, ISLAMIC REPUBLIC OF, ⁴School of Medicine,, Shiraz University of Medical Sciences, Shiraz, IRAN, ISLAMIC REPUBLIC OF, ⁵College of Medicine,, Alfaisal University,, Riyadh, SAUDI ARABIA, ⁶Cancer Institute, St Elizabeth Healthcare, Edgewood, KY.

BACKGROUNDBreast cancer is the most diagnosed cancer in women and a leading cause of cancer-related morbidity. Active treatments, such as chemotherapy, radiation, and targeted therapies, are frequently associated with fatigue, reduced physical activity, and decreased quality of life. Wearable activity trackers, including fitness bands and smartwatches, are increasingly being integrated into oncology care to track physical activity, monitor symptoms, and enhance patient engagement. Their use during active treatment provides new opportunities for behavioral support and real-time, remote monitoring. This study systematically examines the use of wearable activity trackers during active breast cancer treatment to monitor activity, track symptoms, support adherence, and enhance patient engagement.METHODSA comprehensive search using relevant keywords and MeSH terms related to ‘breast cancer’, ‘breast cancer treatment’, and ‘activity trackers’ was conducted until March 2025 across PubMed/Medline, Scopus and Web of Science. Studies that used wearable activity trackers in adult breast cancer patients receiving active treatment as part of clinical care or research were included. Data were systematically extracted on how activity trackers were used during active treatment and their intended purposes. The findings were synthesized narratively.RESULTSThe final analysis comprised 40 studies involving over 8,000 participants. The included studies comprised of observational studies (prospective, longitudinal, and cohort) (n=25), randomized controlled trials (n=9), cross-sectional studies (n=4), and non-randomized interventional studies (n=3). Most studies (n = 18) were conducted in the United States. The most common wearable tracker was FitBit. Wearables were primarily used to track physical activity, assess symptoms such as fatigue and sleep issues, and enhance patient engagement and treatment adherence. 23 studies (57.5%) assessed physical activity, 18 (45%) studies assessed sleep, 10 (25%) studies evaluated fatigue, and 9 studies (22.5%) examined quality of life. 21 studies described adherence outcomes, with adherence rates ranging from roughly 16.9% to 96%, while 23 studies (57.5%) reported feasibility outcomes. The duration of time using wearables varied across studies. CONCLUSIONThis study demonstrated that wearable activity trackers are practical and can be effectively utilized during active breast cancer treatment to monitor physical activity, sleep, and fatigue, while also supporting patient engagement and adherence. Most studies demonstrated high feasibility and acceptable adherence rates, underscoring the potential of these devices to enhance supportive care. With technological advancements, wearable trackers offer the potential for real-time detection of treatment-related toxicities and delivery of personalized interventions. Future research is needed to validate wearable-derived metrics and support their integration into clinical decision-making pathways, thereby optimizing outcomes in breast cancer care. Other future directions include leveraging wearables for tracking lymphedema, monitoring long-term cardiac health following anthracycline exposure, and evaluating toxicity profiles associated with the rise of HER2-targeted antibody-drug conjugates. However, key challenges remain, including data overload, limited integration with electronic medical records, and persistent issues of equity and access. Collaborating with companies to incorporate wearable data collection in clinical trials may help address these barriers, while efforts to ensure rigorous validation and standardization of wearable technologies will be critical to their successful adoption in routine oncology care.

P. Chalela¹, V. Cortez¹, S. Sivak¹, A. Flores¹, Z. Garcia¹, M. Duran¹, S. Sierra¹, M. Sung-Cuadrado¹, A. Trejo¹, S. Basoor¹, B. Choi², E. Munoz¹, C. Despres¹, A. Gonzalez¹, V. Kaklamani³, K. Lathrop³, M. Mazo Canola³, D. Inupakutika⁴, D. Akopian⁴, A. G. Ramirez¹; ¹Institute for Health Promotion Research, UT Health San Antonio, San Antonio, TX, ²Population Health Sciences, UT Health San Antonio, San Antonio, TX, ³Mays Cancer Center, UT Health San Antonio, San Antonio, TX, ⁴Software Communication and Navigation Systems Laboratory, University of Texas at San Antonio, San Antonio, TX.

Background: Hormone therapy (HT) significantly lowers the risk of recurrence and mortality for patients with hormone receptor-positive breast cancer, which accounts for roughly 80% of all breast cancer cases. Long-term adherence to HT can cut recurrence rates by nearly 50%. Yet, about one-third of women prescribed HT are non-adherent, taking less than 80% of the recommended daily dose. Latina patients are disproportionately affected by Non-Medical Drivers of Health (NMDoH), such as socioeconomic and access-related barriers, that hinder adherence and contribute to poorer outcomes. Objective: This three-arm randomized controlled trial evaluates the comparative effectiveness of a bilingual, culturally tailored mobile app (HT Helper) combined with Patient Navigation (PN), PN alone, and standard care on improving HT adherence. The study also examines how these interventions influence self-efficacy in recognizing and managing side effects and enhancing communication with healthcare providers. This work builds on earlier pilot findings that confirmed the HT Helper app’s feasibility and acceptability. We present key findings from the formative phase, including usability testing, focus group feedback, and final app modifications. Methods: Twelve Latina breast cancer patients receiving HT at the Mays Cancer Center and experiencing NMDoH-related barriers participated in the formative research activities. Participants used the HT Helper app for one week and then joined focus groups (conducted in their preferred language, English or Spanish) to provide in-depth feedback. Participants reviewed and commented on all app components, including navigation, educational videos, symptom-tracking tools, motivational messaging, the Chat with a Doctor feature, and the User Guide. Based on their recommendations, we updated the app and conducted a second round of testing. Findings: Most participants responded favorably to the HT Helper app, describing it as helpful, informative, and easy to use. Suggestions for improvement included expanding descriptions of specific HT-related symptoms, enhancing the app’s interactive features (e.g., Chat with a Doctor), updating patient testimonial videos, and refining the visual design of the home screen for better appeal and usability. Conclusion: A patient-driven, iterative refinement process was critical to ensuring the HT Helper app is user-friendly, relevant, and responsive to the needs of Latina patients. The resulting multi-component intervention has strong potential to improve breast cancer outcomes by enhancing medication adherence, promoting better self-management, and ultimately supporting longer-term survival. The intervention is designed to be scalable, evidence-based, and suitable for broader use among patients prescribed oral anticancer therapies.

N. Ganatra, A. Jamal, P. Jain, J. Doshi, S. Patel; Internal Medicine, Baptist Hospitals of Southeast Texas, Beaumont, TX.

Background:Sequential, timely delivery of multimodal treatment is essential to optimal outcomes in breast cancer. The majority of previous studies determine delays in treatment in isolation, without including disruptions across the entire treatment cascade (surgery → chemotherapy → radiation → hormone/immunotherapy). This study examines socioeconomic predictors of sequential and cumulative delays in the treatment of breast cancer. Methods:We conducted a retrospective cohort study on registry data from 609 breast cancer patients treated between 2018 and 2023 at a Southeast Texas multi-hospital system. Delay was classified as determined by modality-specific time thresholds as defined. Patients were classified as having 0, 1, 2, 3, or ≥4 modality delays. Logistic regression examined associations with demographic, insurance, and tumor characteristics. Results:53% of patients experienced one or more modality delays; 19% had ≥2 modality delays.Medicaid insurance (OR: 2.89, 95% CI: 1.70-4.92), age <50 (OR: 2.15, CI: 1.30-3.54), and unmarried status (OR: 1.76, CI: 1.22-2.54) were independent predictors of cumulative delay.Triple-negative patients (subset analysis, n = 98) with ≥2 delays had higher stage progression rates than on-time-treated counterparts (p = 0.03).Cascade analysis showed the greatest drop-off rate was after surgery (not initiating adjuvant chemotherapy or radiation). Conclusion:Delays in breast cancer care are not isolated events. Medicaid status, younger age, and social isolation are predictors of cumulative care disruption. Interventions must address continuity of all treatment cascade steps, especially among socioeconomically disadvantaged groups.

A. Blasco¹, P. Zamora-Auñón², R. Pastor³, M. Martín⁴, C. Reboredo⁵, A. Lahuerta-Martinez⁶, I. Álvarez⁶, S. Sonia⁷, M. Marin⁸, E. Martínez de Dueñas⁹, J. López-Vega¹⁰, A. Barnadas¹¹, Á. Rodríguez-Lescure¹², S. Salvador-Bofill¹³, C. Jose Ignacio¹⁴, V. Lope¹⁵; ¹Statics, GEICAM Spanish Breast Cancer Group; PhD Program in Medicine and Surgery. Doctoral School, Universidad Autónoma de Madrid, San Sebastián de los Reyes, SPAIN, ²Medical Oncology, Hospital Universitario La Paz; PhD Program in Medicine and Surgery. Doctoral School, Universidad Autónoma de Madrid; GEICAM Spanish Breast Cancer Group, Madrid, SPAIN, ³Epidemiology and cancer area, National Centre for Epidemiology, Instituto de Salud Carlos III; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP), Madrid, SPAIN, ⁴Medical Oncology, Hospital General Universitario Gregorio Marañón: Instituto de Investigación Sanitaria Gregorio Marañón, Centro de Investigación Biomédica en Red de Oncología, CIBERONC-ISCIII, GEICAM Spanish Breast Cancer Group, Madrid, SPAIN, ⁵Medical Onco, Complejo Hospitalario Universitario A Coruña (CHUAC); GEICAM Spanish Breast Cancer Group, A Coruña, SPAIN, ⁶Medical Oncology, Unidad de Gestión del Cáncer de Guipúzcoa (Osakidetza-OSI Donostialdea_Onkologikoa)-BioDonostia; GEICAM Spanish Breast Cancer Group, San Sebastián, SPAIN, ⁷Medical Oncology, Hospital del Mar; GEICAM Spanish Breast Cancer Group, Barcelona, SPAIN, ⁸Medical Oncology, Consorci Sanitari de Terrassa; GEICAM Spanish Breast Cancer Group, Terrasa, SPAIN, ⁹Medical Oncology, Consorcio Hospitalario Provincial de Castellón; GEICAM Spanish Breast Cancer Group, Castellón, SPAIN, ¹⁰Medical Oncology, Hospital Universitario Marques de Valdecilla; GEICAM Spanish Breast Cancer Group, Santander, SPAIN, ¹¹Medical Oncology, Hospital de la Santa Creu i Sant Pau, IR Sant Pau, CIBERONC-ISCIII; GEICAM Spanish Breast Cancer Group, Barcelona, SPAIN, ¹²Medical Oncology, Hospital General Universitario de Elche; GEICAM Spanish Breast Cancer Group, Elche, SPAIN, ¹³Medical Oncology, Hospital Universitario Virgen del Rocio; GEICAM Spanish Breast Cancer Group, Sevilla, SPAIN, ¹⁴Medical Oncology, Hospital Universitario de Toledo; GEICAM Spanish Breast Cancer Group, Toledo, SPAIN, ¹⁵Cancer epidemiology and cancer area, National Centre for Epidemiology, Instituto de Salud Carlos III; Consortium for Biomedical Research in Epidemiology and Public Health (CIBERESP); GEICAM Spanish Breast Cancer Group, Madrid, SPAIN.

Background: The multicenter, open-label, randomized phase III GEICAM/2003-02 study compared two regimens as adjuvant therapy for node-negative breast cancer (BC) patients: FAC (5-fluorouracil, doxorubicin, and cyclophosphamide) alone versus FAC plus weekly paclitaxel (FAC-wP). It demonstrated paclitaxel chemotherapy (CT) improved disease-free survival [1]. This study aims to compare health-related quality of life (HRQoL) in these arms of treatment. Methods: Early-BC patients from the GEICAM/2003-02 study were selected (157 FAC arm and 141 FAC-wP arm). HRQoL was assessed using the EORTC QLQ-C30 version 3.0 questionnaire. Random intercept lineal model with two nested levels (hospital and subject) for repeated measures adjusted by patient and tumor characteristics at diagnosis (body mass, age, histopathological grade, surgery type, stage, tumor subtype and menopausal status) were used to assess changes in the global, functional and symptom QLQ-C30 summary scores from baseline to end of treatment and 6 months later. Stratified analyses were also performed by menopausal status and endocrine-therapy (ET) post-CT according to tumor subtype. Results: QLQ-C30 summary score significantly decreased from baseline to end of treatment (FAC: [-2.08, 95% CI= -7.11, 2.94] and FAC-wP: [-2.82, 95% CI: -7.76, 2.13]) but slightly exceeded baseline scores 6 months post-treatment, with no significant differences between the two arms. Greater deterioration in post-treatment functional summary score was observed in the FAC-wP arm [-4.15, 95%CI: -10.40, 2.11], compared to FAC [-1.46, 95% CI= -7.78, 4.86]. In postmenopausal patients, post-treatment QLQ-C30 summary score deterioration was greater in the FAC-wP arm [-4.05, 95% CI= -9.96, 1.86]. Hormone receptor positive, human epidermal growth factor receptor 2 negative (HR+ HER2-) with ET post-CT patients showed more pronounced reductions in the QLQ-C30 summary score post-treatment (FAC: [-3.58, 95% CI= -8.42, 1.27] and FAC-wP: [-5.03, 95% CI: -9.77, -0.28]) than triple-negative patients (FAC: [-2.53, 95%CI= -7.43, 2.37] and FAC-wP: [1.05, 95% CI= -4.05, 6.16]). Further details are shown in Table 1. Conclusions: Taxane-based regimens do not have a great impact on HRQoL recovery after 6 months of treatment: While temporary deterioration in functional and symptom scales was observed during treatment, patients in both arms recovered their baseline HRQoL scores 6 months later. These results also emphasize the importance of considering patient characteristics variables when evaluating HRQoL outcomes in BC survivors. References: 1. M. Martín et al., “Fluorouracil, Doxorubicin, and Cyclophosphamide (FAC) Versus FAC Followed by Weekly Paclitaxel AsAdjuvant Therapy for High-Risk, Node-Negative Breast Cancer: Results From the GEICAM/2003-02 Study,” JCO, vol. 31, no.20, Jul. 2013.

S. A. Roberts¹, A. M. Kagerer¹, N. J. Sareen¹, T. Haque², P. Razavi³; ¹Internal Medicine, NewYork-Presbyterian Weill Cornell Medical Center, NEW YORK, NY, ²Department of Medicine, Leukemia Service, Memorial Sloan Kettering Cancer Center, NEW YORK, NY, ³Department of Breast Oncology, Memorial Sloan Kettering Cancer Center, NEW YORK, NY.

Introduction: Chemotherapy continues to be a pillar of treatment for breast cancer (BC), and while it improves survival and reduces recurrence, there are significant side effects to acknowledge. One of the most serious long-term complications is the development of myeloid neoplasms post cytotoxic therapy (MN-pCT) (previously referred to as therapy-related myelodysplastic syndromes or acute myeloid leukemia). Individuals that developMN-pCTs have significant morbidity and reduction of overall life expectancy, despite improved breast cancer outcomes. The risk of developing t-AML/MDS in breast cancer patients who undergo chemotherapy compared to those who have not had chemotherapy has not been previously reported. Methods: To address this gap, we conducted a systematic review and meta-analysis to quantify the risk of MN-pCT among breast cancer patients treated with chemotherapy compared to those who did not receive chemotherapy. PubMed, Embase, and Cochrane databases were searched in March 2025. The search strategy included three search strings: breast cancer, leukemia or myelodysplastic syndrome or hematologic malignancy, and chemotherapy. Included articles were experimental or observational studies. Full texts were independently reviewed by two reviewers, with discrepancies resolved via consensus. The primary outcome was the pooled odds ratio (OR) for the development ofMN-pCT following chemotherapy exposure in BC patients compared to those who did not receive chemotherapy. Random-effects meta-analysis was used to calculate pooled ORs and 95% confidence intervals (CIs). Publication bias was assessed using visual inspection of the funnel plot and Egger’s test for small-study effects. Heterogeneity was assessed with the I² statistic, and meta-regression explored the impact of study-level factors such as anthracycline use, radiation, follow-up duration, publication year, age, and sample size. Results: Nineteen studies from 1985 to 2023 met inclusion criteria and included a total of 1,215,260BC patients (527,761 chemotherapy; 687,499 no chemotherapy). The studies consisted of2 randomized controlled trials, 1 case control study, and 16 retrospective cohort studies.The median follow-up time was 5.8 years. The pooled incidence of MN-pCT was 0.31%(chemotherapy) and 0.23% (no-chemotherapy). Chemotherapy was associated with an early two-fold increase in risk of AML/MDS (pooled OR 1.91 (95% CI: 1.41-2.58), p <0.001), with substantial heterogeneity (I² = 82.9%). The estimated between-study variance(τ²) was 0.1810 (SE = 0.1167). Meta-regression showed that the proportion of patients receiving anthracyclines explained over half of the between-study heterogeneity (R² =56.3%) but was not a statistically significant predictor of risk (p = 0.21). Notably, non-anthracycline regimens were also associated with a significant increase in MN-pCT risk.No significant associations were found for publication year, sample size, follow-up duration, age, or radiation exposure. Conclusion: We present the first meta-analysis that directly compares the risk of MN-pCT in patients with breast cancer who received cytotoxic chemotherapy versus those who did not receive chemotherapy. This risk was not confined to a specific regimen and is likely multifactorial in nature. Our results highlight the importance of risk-benefit discussions when pursuing chemotherapy, especially taking into consideration co-morbidities, life expectancy, and breast cancer risk profile. Additionally, future studies are needed to optimize surveillance strategies and develop and validate biomarkers to identify patients at risk of MN-pCTs after chemotherapy exposure.

S. Tapiavala¹, I. Grigsby¹, N. Bagegni¹, F. Fa’ak¹, F. Ademuyiwa¹, K. Clifton¹, E. L. Podany¹, C. Cheng², A. J. Medford³, C. Gianni⁴, L. Gerratana⁵, M. Lipsyc-Sharf², A. Bardia², M. Cristofanilli⁴, C. X. Ma¹, A. A. Davis¹; ¹Division of Oncology, Washington University in St. Louis, St. Louis, MO, ²Division of Hematology/Oncology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA, ³Division of Oncology, Massachusetts General Hospital, Boston, MA, ⁴Department of Oncology and Hematology-Oncology, Weill Cornell Medicine, New York, NY, ⁵Department of Medical Oncology, IRCCS CRO Aviano National Cancer Institute, Aviano, ITALY.

Background: There are no standard guidelines regarding radiographic or laboratory monitoring for patients with early-stage breast cancer (EBC) in the adjuvant setting. Detecting minimal residual disease (MRD) through circulating tumor DNA (ctDNA) is associated with significantly higher probability of later distant recurrence, although clinical utility data are lacking. To date, patient understanding and emotional burden of serial MRD testing are understudied. Here we evaluate the impact of MRD surveillance on quality of life among patients with EBC through investigating anxiety, depression, fear of recurrence, and patient comprehension. Methods: This IRB-approved prospective study enrolled patients with EBC undergoing ctDNA surveillance testing at Washington University in St. Louis. All patients underwent blood collection for Signatera MRD testing (Natera Inc.) and plasma-biobanking at up to 8 serial timepoints over 4 years. Baseline testing was prior to neoadjuvant treatment (n=12) or after surgery prior to adjuvant therapy (n=29). Testing results were shared with the patient and the treating oncologist. Surveys were conducted to assess patient understanding of the rationale for ctDNA testing, Fear of Recurrence (FCR4), Hospital Anxiety and Depression Scale (HADS), and level of comfort with ctDNA testing, at baseline blood collection and again 12 months after the initial MRD testing. Qualitative data were obtained through free-response survey items. Descriptive statistics were used to summarize the data. Results: 41 patients with triple-negative (n=17) or HR+ HER2- (n=24) EBC completed the baseline surveys with 26 patients completing both the baseline and 12-month assessments as of July 1^st, 2025. The cohort included 31 (75.6%) White, 8 (19.5%) Black, and 2 (4.9%) Asian patients with a median age of 50 years. Qualitative analysis demonstrated patients had a strong understanding of the use of ctDNA surveillance with 30 of 35 (85.7%) patients who responded to the free text question accurately describing it as a tool for early detection of cancer in the blood. At 12 months, 88.5% of patients (n=23 of 26) answered that they would consider starting treatment based on results of ctDNA testing if recommended by their oncologist; however, 42.3% of patients (n=11 of 26) expressed financial concern with ctDNA testing if not covered by insurance. Among patients with longitudinal survey data (n=26), 10 patients had at least one positive MRD test and one patient had serially positive MRD testing prior to 12-month surveys. For patients with negative MRD testing at all timepoints (n=16), the mean FCR4 score did not significantly change from baseline to 12 months. Similarly, for those with positive MRD testing (n=10), FCR4 score did not significantly change at 12 months. The average HADS-anxiety score decreased from 5.15 at baseline (n=40) to 4.54 at 12 months (n=26), while the average HADS-depression score increased from 1.89 to 2.52; however, this change was not significant, including in the subset of patients with positive MRD testing. On a 0-5 scale of evaluating future attitudes toward use of ctDNA testing, the average rating was 4.1, indicating a favorable opinion of undergoing MRD testing. Conclusion: This prospective study demonstrated that the rationale for MRD testing was well understood and viewed favorably by patients. Regardless of MRD testing results, fear of recurrence and levels of anxiety or depression remained relatively stable from baseline to 1 year, indicating that testing was not associated with significant psychological stress in our study. Nearly half of patients expressed concerns about costs associated with testing if not covered by insurance. Larger, confirmatory studies are needed to further evaluate the impact of MRD surveillance on quality of life of patients with EBC.

K. Lampson¹, X. Li¹, A. Yang², S. N. Garland³, J. C. Root², T. A. Ahles², J. J. Mao¹; ¹Integrative Medicine, Memorial Sloan Kettering Cancer Center, New York City, NY, ²Department of Psychiatry and Behavioral Sciences, Memorial Sloan Kettering Cancer Center, New York City, NY, ³Department of Psychology and Oncology, Memorial University of Newfoundland, St. John’s, NL, CANADA.

Background: Cancer-related cognitive difficulties (CRCD) is prevalent and distressing for breast cancer survivors and commonly co-occurs with insomnia. Although sleep tracking has become increasingly common in oncology settings, little is known about how sleep patterns influence cognition in cancer survivors. Therefore, we aim to characterize the associations between subjective and objective sleep continuity and cognition in breast cancer survivors with insomnia and CRCD. Methods: This analysis includes baseline data from a trial conducted among 260 breast cancer survivors with insomnia (Insomnia Severity Index score 8) and self-reported CRCD. This analysis is limited to trial participants who completed sleep tracking measures, including the Consensus Sleep Diary (CSD) and Actiwatch or FitBit smart watch (WA). Sleep continuity measures included wake after sleep onset (WASO), number of awakenings (NWAK), time spent in bed (TIB), total sleep time (TST), and sleep efficiency (SE). Subjective cognition was assessed by Functional Assessment of Cancer Therapy-Cognition Perceived Cognitive Impairment domain (FACT-Cog PCI), while objective cognition was assessed by Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall normed T-score. Multivariate linear regression modeling was used to explore associations between sleep continuity and cognition. All models included adjustments from covariates: chemotherapy use, cancer stage, race, and education. Results: Among 158 participants, the average age [range] was 57 [28-83] and 21.5% were nonwhite. None of the sleep metrics collected from either the CSD or WA were significantly associated with subjective cognition (all p > .05). In data collected by CSD, greater WASO was significantly associated with worse objective cognition (Coef. = -.243, p = .003, 95% CI [-0.135, -0.028]) and higher SE was significantly associated with better objective cognition (Coef. = .209, p = .011, 95% CI [0.054, 0.422]). In data collected by WA, greater NWAK was significantly associated with worse objective cognition (Coef. = -.298, p = .010, 95% CI [-0.294, -0.042]). Conclusion: Measured and reported sleep continuity was not significantly associated with subjective cognition, but sleep fragmentation, measured by both sleep diary and smart watch, was significantly associated with worse objective cognition in breast cancer survivors with comorbid insomnia and CRCD. Interventions targeting sleep could be used to promote cognitive health during breast cancer survivorship.

J. Avila¹, X. Xue², A. Gyamfi³, J. D. Anampa³; ¹Department of Hematology and Medical Oncology, Montefiore Medical Center, Bronx, NY, ²Department of Epidemiology, Albert Einstein College of Medicine, Bronx, NY, ³Department of Oncology, Montefiore Einstein Cancer Center, Bronx, NY.

Background:While patients with early-stage invasive lobular carcinoma (ILC) of the breast often present better survival rates initially, the risk of recurrence and mortality increases later in the disease course. The Clinical Treatment Score Post-5 years (CTS5) is a validated tool used to estimate risk of late distant recurrence in patients with Hormone Receptor positive breast cancer after 5 years of adjuvant treatment; however, its application in patients with ILC has not been fully analyzed. OncotypeDx provides prognostic information in breast cancer, but there is limited data about OncotypeDx to predict long-term survival outcomes in ILC. We aimed to assess whether CTS can predict long-term OS for patients with ILC, and to evaluate its prognostic effect beyond OncotypeDx recurrence score. Methods:We conducted a retrospective analysis using the National Cancer Database (NCDB) from 2006-2020. Inclusion criteria were female gender, age ≥18 years, diagnosis of ILC, breast cancer stage I-III, removal of breast tumor and axillary lymph nodes, and alive status at least 5 years after diagnosis. Patients were classified into CTS5 low, intermediate and high-risk categories. Our primary endpoint, long-term overall survival (OS) included survival analysis after 5 years from diagnosis. We used the Pearson X² test to evaluate the relationship between categorical variables and the t test for continuous variables. Cox proportional models were conducted to identify factors associated with long-term OS. Results:67,927 patients were analyzed for our long-term survival analysis. Median age for our group was 63 years. Most of our patients were Non-Hispanic White (82%), with breast cancer stage I (50%), HR positive (ER+ [100%], PR+ [87%])/HER2 negative (73%) tumors. Patients were divided into 3 groups based on their CTS5 risk: low (n = 32,625 [48%]), intermediate (n = 21,007 [31%]) and high (n = 14,295 [21%]). 10-year OS rates differed significantly among these groups with OS rates of 91%, 84% and 64% respectively (p < 0.001 each). In multivariate Cox regression models adjusted for patient, tumor, and treatment characteristics, CTS5 remained an independent predictor of long-term OS. Patients with high CTS5 score had worse long-term OS when compared to those with low CTS5 (HR 3.63, 95% CI 3.42-3.86; p <0.001). We also analyzed 17,882 patients from the long-term cohort with available OncotypeDx results. Among patients with high OncotypeDx recurrence score, the percentage of patients with low, intermediate, and high CTS5 risk-group were 47.3%, 41.3%, 11.4% respectively, whereas the percentages were 50.9%, 38.6%, and 10.5% for those with low OncotypeDx recurrence score. We found that CTS5 provided significant prognostic information for long-term OS across all Oncotype Dx risks group. Patients with high CTS5 risk-group had worse long-term OS when compared to those with low CTS5 risk-group in patients with low (HR 4.6, 95% CI 2.90-7.30; p <0.001), intermediate (HR 4.33, 95% CI 3.43-5.46; p <0.001), and high (HR 3.99, 95% CI 2.19-7.28; p <0.001) OncotypeDx recurrence score. A multivariable model with CTS5 in addition to OncotypeDx recurrence score showed significant association with long-term OS (Likelihood ratio test, p <0.001). Conclusion:CTS5 is an independent predictor of long-term OS in patients with ILC and it can identify patients with substantially higher risk of late death beyond 5 years. CTS5 adds independent prognostic information that persists even after adjusting for genomic factors such as OncotypeDx recurrence score. Combining CTS5 score and OncotypeDx recurrence score into clinical practice may provide better information for treatment decisions such as extending endocrine therapy or intensifying surveillance in this population.

K. M. Woolpert; Department of Clinical Epidemiology, Aarhus University and Aarhus University Hospital, Aarhus N, DENMARK.

Background: Opioids are frequently prescribed to manage pain after a breast cancer diagnosis, but prolonged use can lead to serious harm, including dependence and overdose. Socioeconomic position (SEP), often defined by income, education, and employment, may influence access to care, prescribing patterns, and the likelihood of long-term opioid use. Although Denmark provides universal healthcare, it is unclear whether SEP-related differences in opioid use persist after diagnosis. Methods: We identified all patients assigned female at birth who were diagnosed with non-metastatic breast cancer at age 18 or older between 1997 and 2020 using the Danish Cancer Registry. Patients with opioid use or a hospital history of opioid use disorder in the year before diagnosis were excluded. To be eligible, patients had to survive and reside in Denmark for at least one year after diagnosis. SEP was measured at diagnosis using household income, education level, and employment status. We defined three outcomes from the time of diagnosis: any opioid use (≥1 prescription within 6 months), prolonged use (≥1 prescription in the first 6 months and ≥2 in months 6-12), and opioid-related disorder or overdose within 5 years. Associations between SEP and each outcome were estimated using logistic regression, reporting crude odds ratios (OR) and 95% confidence intervals (CI). Results: Among 77,261 one-year breast cancer survivors, 52,321 (68%) redeemed an opioid prescription within six months of diagnosis, 992 (1.3%) became prolonged users, and 204 (0.3%) experienced an opioid-related disorder or a fatal/non-fatal overdose. Patients with low income were more likely to receive any opioid in the first six months after diagnosis compared with those with high income (OR: 1.40, 95% CI: 1.34, 1.46), with similar patterns observed across other measures of SEP. Among those who received opioids, there were no SEP differences in the type or strength prescribed. Unemployed patients were more likely to become prolonged users compared with those employed at diagnosis (OR: 1.68, 95% CI: 1.47, 1.93), and patients with a high-school education had higher odds of opioid-related disorder or overdose compared with those with a tertiary-level education (OR: 1.74, 95% CI: 1.21, 2.50). Discussion: In this nationwide study of breast cancer survivors, socioeconomic differences in opioid use and harms emerged despite universal healthcare. Although initial prescribing practices appeared equitable among users, patients with lower SEP were more likely to receive opioids, become prolonged users, and experience opioid-related harm. These findings highlight the need for equity-focused pain management and survivorship care in breast cancer. Because this was a descriptive study, we reported crude estimates to reflect overall patterns. Future work could build on these findings by exploring potential mechanisms or points for intervention.

J. Song¹, R. Liu², S. K. Zhong³, P. Mishra³, S. Zhu³, E. Feliciano³; ¹Internal Medicine, Kaiser Permanente Northern California, Santa Clara, CA, ²Hematology/Oncology, Kaiser Permanente Northern California, San Francisco, CA, ³Division of Research, Kaiser Permanente Northern California, Pleasanton, CA.

Background Obesity and diabetes are common comorbid conditions found in patients with breast cancer and these conditions have been linked to risk of recurrence and early mortality. GLP-1 receptor agonists have changed the paradigm for weight loss and diabetes management, but the prevalence, timing of initiation and duration of use among women with a breast cancer history is not well described. Further, efficacy for weight loss may vary by diabetes status and treatment factors such as the use of endocrine therapy. Methods To address these knowledge gaps, our retrospective analysis utilized tumor registry and electronic health record data to identify all patients with a breast cancer history who initiated semaglutide (and/or tirzepatide) therapy from 2020-2025 at Kaiser Permanente Northern California, a large integrated community oncology network in the US. Results 1,753 patients with breast cancer history initiated semaglutide in the years 2020-2025. The majority of patients were diagnosed with stage 0 or I/II breast cancer (344 [19.6%] and 1,146 [65.4%], respectively) and 1,456 (83.1%) of patients had estrogen receptor (ER) positive breast cancer. 1,245 (71.0%) had diabetes at initiation. The average age at initiation was 63.5 years, with a median (IQR) time from breast cancer diagnosis to semaglutide initiation of 7 (3-13) years. 1,296 (73.9%) had ever used endocrine therapy, with 685 (39.1%) on active endocrine therapy at semaglutide initiation. Most patients had >1 semaglutide dispense (1,718 [98.1%]), but more than one third continued use beyond 1 year. Mean (SD) BMI at semaglutide initiation was similar among the non-diabetic (37.4 [7.2] kg-m2) vs. the diabetic (36.4 [7.5] kg/m2) group, with a mean maximum achieved weight loss of 11.2% and 8.6%, respectively. When stratified by history of endocrine therapy, rates of continuation at one year and achieved weight loss were similar between groups. Conclusion In patients with breast cancer, semaglutide therapy was most commonly initiated for diabetes and was associated with weight loss, even among those receiving endocrine therapy. However, the maximum observed weight loss was less than that observed in clinical trials in non-cancer populations. Long-term adherence was limited, with only one-third continuing use beyond one year. Our study highlights the role of real-world data in understanding the effects of GLP1- receptor agonist drugs in patients with breast cancer. Future studies should investigate whether the use of these agents reduces risk of recurrence and mortality.

S. Bluethmann¹, E. Dressler², M. Caru³, H. Klepin⁴, A. Willis², C. Truica⁵, C. Peters¹, N. Olsen⁵; ¹Div. Public Health Sciences, Dept of Social Sciences and Health Policy, Wake Forest University School of Medicine, Winston-Salem, NC, ²Div. Public Health Sciences, Dept of Biostatistics and Data Science, Wake Forest University School of Medicine, Winston-Salem, NC, ³Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, ⁴Division of Hematology and Oncology, Wake Forest University School of Medicine, Winston-Salem, NC, ⁵Department of Internal Medicine, Penn State College of Medicine, Hershey, PA.

Background: Aromatase inhibitors (AIs) reduce recurrence and mortality risk in estrogen receptor-positive female breast cancer survivors (BCS), the majority of whom are aged ≥60. However, up to 70% of users discontinue AIs before the recommended duration of therapy, often due to arthralgia, which affects more than 50% of AI users. Despite its prevalence, AI-associated joint pain remains poorly understood, particularly in older survivors. Physical activity (PA) and education may mitigate symptoms and support adherence, yet tailored interventions for this population are lacking. Methods: We tested REJOIN (Relieving Joint Pain and Improving AI Adherence in Older Breast Cancer Survivors), a remotely delivered, supervised exercise and education intervention. We recruited through two sites (Penn State Cancer Institute and Atrium Health Wake Forest Baptist Comprehensive Cancer Center). The pilot randomized controlled trial (RCT) assessed feasibility and early evidence of benefit. Participants (n=24 BCS) received a 16-week, program including resistance and aerobic training, education on AI-related side effects, and self-management strategies. Joint pain was measured via the Brief Pain Inventory (BPI), and AI adherence via the Morisky-Levine Medication Adherence Scale at baseline, 4, 6 and 12 months. Additional measures included physical activity (collected via Actigraph triaxial research-grade accelerometer), modified geriatric assessment battery and a fasting blood draw. Descriptive statistics were calculated for each outcome at baseline, 4 months and the change in-between the two time points to assess effects from the intervention. Between group differences in change were assessed using the Wilcoxon rank-sum test and within-group changes using the Wilcoxon signed-rank test (α=0.05). Effect sizes were calculated using Cohen’s d with corresponding 95% confidence intervals to estimate magnitude of changes within and between groups; values of d≥0.5 indicate moderate or greater practical significance. Results: Participants’ mean age was 72 years (range 60-88), included >33% from rural areas, and we had 80% retention over the 12 month pilot study. Our study revealed a moderate reduction in joint pain interference (d = -0.465, p=0.43) and a practically significant increase in AI adherence (d = 0.632, p=0.22) from baseline to 4-months post-intervention compared to standard care. From this pilot, we also determined that the exercise-based intervention was safe (no severe adverse event), feasible (we were able to recruit older BCS and complete the intervention) and acceptable (mean 9.7/10 likelihood of recommending to a friend). In accelerometry data, we observed increased physical activity from baseline to post-intervention at four months, and evidence that activity was more effectively maintained by the exercise group compared to standard care over four research assessments. Future Directions A future randomized efficacy trial will test REJOIN among BCS aged ≥60 within one year of initiating AI therapy. The primary outcome will be joint pain interference during daily activity and the secondary outcome will include AI adherence. As part of this future study, we aim to investigate the biological mechanisms driving AI-related joint pain in older breast cancer survivors, focusing on inflammatory biomarkers such as IL-6, TNFα, and CRP. This will provide evidence to clarify origins of AI-related joint pain and inform future therapeutic strategies. Conclusions: REJOIN offers a scalable approach to reduce AI-associated joint pain and support medication adherence in older BCS. This intervention addresses a critical survivorship gap in older adults and may improve quality of life and treatment outcomes, especially in rural and understudied populations.

A. Broderick¹, S. Hatcher¹, R. B. D’Agostino, Jr.², N. O’Connell², R. Bansal¹, C. Anders¹, S. Telloni¹, K. Westbrook¹, A. Natarajan¹, N. J. Pagidipati³, D. Wendell⁴, E. Douglas⁵, K. Ansley⁵, C. J. Park⁶, K. M. Richardson⁶, S. R. Sirkisoon⁷, M. Hackney⁸, H. Vachhani⁸, M. Ross⁸, L. N. Vélez-Torres⁹, J. H. Jordan¹⁰, A. Thomas¹; ¹Duke Cancer Institute, Department of Medicine, Duke University, Durham, NC, ²Department of Biostatistics and Data Science, Wake Forest University Health Sciences, Winston-Salem, NC, ³Division of Cardiology, Department of Medicine, Duke University, Durham, NC, ⁴Division of Cardiology, Cardiovascular Magnetic Resonance Center, Duke University, Durham, NC, ⁵Department of Cancer Medicine, Wake Forest School of Medicine, Winston-Salem, NC, ⁶Department of Cardiovascular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, ⁷Clinical Trials Office, Atrium Health Wake Forest Baptist Comprehensive Cancer Center, Winston-Salem, NC, ⁸Division of Hematology, Oncology and Palliative Care, Massey Comprehensive Cancer Center, Virginia Commonwealth University, Richmond, VA, ⁹Division of Hematology, Oncology and Palliative Care, Massey Comprehensive Cancer Center, Virginia Commonwealth University and University of Puerto Rico Comprehensive Cancer Center, Richmond, VA, ¹⁰Pauley Heart Center, Department of Medicine and Department of Biomedical Engineering, Virginia Commonwealth University Health Sciences, Richmond, VA.

Background:  Near complete estrogen deprivation (NCED) with ovarian function suppression and aromatase inhibition improves survival outcomes in premenopausal women with HR+ breast cancer (BC). Despite the association of premature menopause with cardiovascular (CV) morbidity in non-cancer populations, the CV health in premenopausal women undergoing BC treatment remains underexplored. As advanced CV imaging is uncommon and guidelines discourage routine cross-sectional imaging in early-stage BC, cardiac and extracardiac imaging findings in these young women are largely uncharacterized.  Methods: The Cardiac Outcomes with Near-complete Estrogen Deprivation (CROWN) study is an NIH-funded 3-site study utilizing serial stress cardiac magnetic resonance (CMR) and coronary computed tomography angiography (CCTA) to characterize the natural history of CV health in premenopausal women with stage I-III BC receiving NCED for HR-positive disease and for a comparator cohort with HR-negative disease. Here we describe unexpected cardiac and extracardiac findings on baseline CMR and CCTA imaging of CROWN participants and assess whether these findings led to changes in clinical management. Findings noted were categorized as “unexpected” if they were not included in the study’s primary or secondary endpoints which are myocardial perfusion reserve and other surrogates of large and small vessel disease such as coronary calcium. We excluded clinically insignificant findings such as atelectasis, small hiatal hernias, trace valvular regurgitation, and trace effusions.  Results: 72 patients were included (median age of 44 years). 61 patients had HR+ disease (3 HER2+) and 11 had HR- disease (3 HER2+). A total of 37.5% of patients had one or more unexpected finding (37 findings in 27 patients), of which 30 were extracardiac and 7 were cardiac [TABLE]. Of the cardiac findings, 3 were congenital heart disease, 3 were mild structural heart disease, and 1 was a cardiac (vascular) finding. Of all patients, 4.2% were referred to cardiology for management of congenital or vascular (cardiac) findings, and 1.4% were referred for cardiovascular procedures. Further, 9.7% of patients had serial imaging for monitoring of extracardiac findings. 2.8% had a biopsy resulting in diagnosis of BC recurrence. Conclusion:  In this first prospective cohort of premenopausal women with BC undergoing serial advanced CV imaging, unexpected baseline cardiac and extracardiac findings leading to clinical action occurred with some frequency, with a handful of findings being of immediate clinical consequence. These results highlight the need to further understand CV health in premenopausal women with BC as we seek to evaluate the impact of both anti-neoplastic therapy and of cancer itself on women with decades of life to protect. [Full cohort data of 90 participants to be presented at the meeting.]

J. Weathington, I. Lynch, B. Sukhu, T. Glatz, E. Lee; Health Sciences, University of Central Florida, Orlando, FL.

Background: Breast cancer (BC) recurrence risk is highest within the first 5-years following initial diagnosis, making survivorship care a critical window for intervention. As survivorship rates increase, identifying modifiable lifestyle factors that may reduce recurrence risk becomes increasingly important. While the protective factors of recreational physical activity (rPA) before BC diagnosis are well-documented, the role of post-diagnosis rPA, particularly its impact on recurrence remains less explored. Objectives: This study aimed to determine 1) if high levels of post-diagnosis rPA reduce BC recurrence risk in female survivors compared to minimal rPA and 2) if adhering to the Physical Activity Guidelines for Americans (i.e., 150 minutes of moderate-intensity physical activity weekly) reduces recurrence risk. Methods: We included observational cohort studies evaluating the association between post-diagnosis rPA and recurrence risk among adult female BC survivors published up to January 2025, in any language or geographic location. Excluded studies were interventional studies, hospital/clinical studies, male BC survivors, and those under 18 years. Databases (Medline, CINAHL, Web of Science) were searched in February 2025. Two reviewers independently screened studies at all stages. Data synthesis and analysis used pooled risk estimates (RR/HRs) and 95% confidence intervals. A meta-analysis was conducted on Stata using a random-effects model to examine the effects of post-diagnosis of rPA on BC recurrence, separately for minimal vs high rPA and meeting vs not meeting recommended guidelines. Subgroup analyses explored BC subtypes, study characteristics, menopausal status, and follow-up period as potential sources of heterogeneity. Heterogeneity was assessed using Cochran’s Q test and I2 statistics. Results: Out of 2,635 studies screened, 22 passed the initial screening for full-text review, and 9 were included in the meta-analysis (9 high versus low; 5 meeting vs not meeting guidelines). The analysis included 37,787 BC survivors and 4,524 recurrences were reported. Meta-analysis showed that female BC survivors who engaged in high levels of rPA after diagnosis had a 13% lower risk of BC recurrence compared to those with minimal activity (RR=0.87, CI=0.77-0.96, I2=0.00%, n=9). However, meeting the minimum recommendations of rPA alone was not associated with a reduced risk of recurrence (RR=0.93, 95% CI=0.85-1.02, I2=0.00%, n=5). Subgroup analysis showed stronger associations in studies conducted in the Netherlands and Germany, as well as in those with rPA assessment periods greater than 5 years after diagnosis. Using the Newcastle Ottawa Scale, study quality was classified as good (n=7) or fair (n=2). Conclusion: These findings suggest that high levels of rPA postdiagnosis reduces recurrence risk by 13%. Because the current minimum recommendations may not be sufficient to reduce recurrence risk, further research is needed to determine optimal rPA recommendations and guidelines for BC survivors. Additionally, these findings emphasize the value of healthcare professionals promoting higher levels of rPA within survivorship care plans for BC survivors.

P. Niravath¹, M. Rimawi², A. Puri¹, K. Sun¹, H. Mai¹, S. Mathur¹, S. Hilsenbeck², D. Antosh³, R. High³, S. Hoopes³, L. Langsjoen³, A. Brock¹, J. Nangia², J. Chang¹, C. Osborne²; ¹Internal Medicine, Houston Methodist Hospital, Houston, TX, ²Internal Medicine, Baylor College of Medicine, Houston, TX, ³Gynecology, Houston Methodist Hospital, Houston, TX.

Background: Among post-menopausal breast cancer survivors, more than 60% experience atrophic vaginitis, often resulting in impaired quality of life and sexual dysfunction. Nonetheless, vaginal dryness is commonly an unmet need among breast cancer survivors. While vaginal estrogen is a proven, effective treatment for atrophic vaginitis, it has not been adequately studied in Estrogen Receptor-positive (ER+) breast cancer survivors. Methods: In this randomized, controlled, unblinded clinical trial, we enrolled ER+ breast cancer survivors on adjuvant aromatase inhibitor (AI) therapy who were suffering from atrophic vaginitis. Women were assigned to receive either Replens® (a non-hormonal vaginal moisturizer) or vaginal estrogen. Based on patient preference, patients randomized to the estrogen arm chose between 6 months of Vagifem® vaginal tablets (10 mcg daily for the first 2 weeks, then twice a week thereafter) or Estring® vaginal ring (2 mg, placed every 3 months). We tested serum estradiol levels by tandem mass spectrometry (TMS) at several time points in the estrogen arm, and only at baseline & end of study in the Replens arm. Study duration was 24 weeks. The primary endpoint was vaginal dryness, as measured by a validated questionnaire. Secondary endpoints include sexual functioning, vaginal pH, and serum estradiol values Results: Twenty-three patients were enrolled on the study, with 12 patients assigned to the Replens arm. Of the 11 patients assigned to the vaginal estrogen arm, 8 chose Estring and 3 chose Vagifem. The Vaginal Dryness scores (assessed on a scale from 0 to 4) in the estrogen arm improved by an average of 1.6 points, compared to 0.9 points in the Replens arm, which was a statistically significant improvement (p = 0.044). Similarly, there was a more significant reduction in vaginal pH in the vaginal estrogen arm as compared to the non-hormonal treatment, indicating return to healthier vaginal environment in the estrogen arm (p = 0.0286). We observed an improvement in patient-assessed dyspareunia, which was assessed on a scale from 0 to 10. Women on the estrogen arm saw an improvement of 4.8 points, whereas the women receiving nonhormonal treatment improved by an average of 1.7 points (p = 0.048). However, other sexual functioning parameters (libido, ability to achieve orgasm, sexual satisfaction, and relationship with partner) were not significantly different between the 2 groups. Serum estradiol levels remined low through the first 12 weeks in the estrogen arm and exceeded safety threshold (27 pg/mL at 2 weeks, or 12 pg/mL for the remainder of the study) for two of the 11 patients in the estrogen arm at 24 week. One of these patients was taking Vagifem, and her estradiol level rose to 21.8 pg/mL at 6 months. The other patient was using Estring, and her estradiol level increased to 16 pg/mL. Conclusions: Vaginal estrogen is a more effective treatment for vaginal dryness and dyspareunia compared to nonhormonal vaginal moisturizer. Serum estradiol levels remained low for 12 weeks, suggesting this duration of treatment may be considered in select patients. Some patients had an increase in estradiol level at 24 weeks, though its cause and clinical significance are uncertain. Further study is warranted as to why the serum estradiol rise occurred with a longer period of vaginal estrogen treatment.

M. Morita¹, A. Watanabe¹, K. Sakaguchi¹, I. Takashi², Y. Hasegawa³, A. Sato⁴, S. Takao⁵, K. Tane⁶, M. Takahashi⁷, K. Watanabe⁸, M. Kato⁹, Y. Ouchi¹⁰, N. Kono¹¹, T. Kubota¹², M. Suzuki¹³, J. Horiguchi¹⁴, K. Narui¹⁵, D. Miura¹⁶, K. Terata¹⁷, K. Imai¹⁸, R. Takekawa¹⁹, I. Yokota²⁰, A. Naito²¹, S. Sakabayashi¹⁹, Y. Naoi¹, T. Taguchi¹; ¹Department of Surgery, Division of Endocrine & Breast Surgery, Kyoto Prefectural University of Medicine, Kyoto, JAPAN, ²Department of Breast Oncology and Surgery, Tokyo Medical University Hospital, Tokyo, JAPAN, ³Department of Breast Surgery, Hachinohe City Hospital., Aomori, JAPAN, ⁴Department of Medical Oncology, Hirosaki University Graduate School of Medicine, Aomori, JAPAN, ⁵Department of Breast Surgery, Kohnan Medical Center, Hyogo, JAPAN, ⁶Department of Breast Surgery, Hyogo Cancer Center, Hyogo, JAPAN, ⁷Department of Breast Surgery, Hokkaido University Hospital, Hokkaido, JAPAN, ⁸Department of Breast Surgery, Hokkaido Cancer Center, Hokkaido, JAPAN, ⁹Breast Surgery, Kato Breast Clinic, Shiga, JAPAN, ¹⁰Breast Surgery, Saiseikai Shiga Hospital, Shiga, JAPAN, ¹¹Breast Surgery, Kobe Kaisei Hospital, Hyogo, JAPAN, ¹²Department of Breast Surgery, Kamiiida Daiichi General Hospital, Aichi, JAPAN, ¹³Department of Breast Surgery, National Hospital Organization Chiba Medical Center, Chiba, JAPAN, ¹⁴Department of Breast Surgery, International University of Health and Welfare, Chiba, JAPAN, ¹⁵Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, Kanagawa, JAPAN, ¹⁶Breast Surgery, Akasaka Miura Clinic, Tokyo, JAPAN, ¹⁷Department of Breast and Endocrine Surgery, Akita University Hospital, Akita, JAPAN, ¹⁸Department for Medical Innovation and Translational Medical Science, Kyoto Prefectural University of Medicine, Kyoto, JAPAN, ¹⁹Division of Data Science, The Clinical and Translational Research Center, University Hospital, Kyoto Prefectural University of Medicine, Kyoto, JAPAN, ²⁰Department of Biostatistics, Graduate School of Medicine, Hokkaido University, Hokkaido, JAPAN, ²¹Department of Biostatistics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, JAPAN.

Background: Aromatase inhibitors (AIs) are widely used as postoperative endocrine therapy in patients with postmenopausal hormone receptor-positive breast cancer. The main side effect of AIs is bone loss, which is called cancer treatment-induced bone loss (CTIBL), and the use of bone resorption inhibitors are recommended when the risk of fracture is high. However, we do not yet have clear data on the preventive effects of bone resorption inhibitors and their safety in patients with normal bone density. In this study, we aimed to evaluate the preventive effects of denosumab on suppressing bone loss associated with postoperative endocrine therapy for Japanese breast cancer patients with normal bone mineral density.Methods: A multicenter, open-label, randomized controlled trial was conducted. Patients with postmenopausal hormone receptor-positive breast cancer of stage ≦IIIA with normal bone density meeting lumbar spine T-score ≧-1.0 and femoral neck T-score ≧-1.0 were included. Patients were assigned in a 1:1 ratio to receive the hormone alone (control group) or an additional 60 mg of denosumab every 6 months (denosumab group). The primary endpoint was the percentage change in lumbar spine (L1-L4) bone mineral density (BMD) at 12 months. Secondary endpoints included the percentage change in lumbar spine BMD (2-5 years later), femoral neck BMD change, pathological fracture incidence, adverse events, progression-free survival, and overall survival.Results: A total of 83 cases were registered, and 66 were included in the primary analysis. At 12 months, the mean percentage change in lumbar spine BMD was +4.56% in the denosumab group (N=32) and -3.66% in the control group (N=34), yielding a significant improvement of +8.1% (95%CI: 6.2%-10.1%, p<0.01) in analyses adjusting for several covariates in a linear model.Within three years, there were no fractures in the denosumab group and one in the control group (p=0.53). Adverse events of any grade occurred in 13 cases (33.3%) in the denosumab group and 12 (31.6%) in the control group; there were no cases of osteonecrosis of the jaw or atypical femoral fractures. No significant differences were observed in disease-free survival or overall survival.Conclusion: In Japanese breast cancer patients with normal bone density, the combination of denosumab and postoperative adjuvant endocrine therapy significantly prevented the decline in lumbar spine BMD. This intervention showed a good safety profile without severe adverse events and the potential to prevent the occurrence of fractures. These findings support the consideration of denosumab as part of a comprehensive strategy for preserving bone health in a broader range of patients, including those with initially normal BMD who are receiving endocrine therapy for breast cancer. Future research should aim to explore long-term fracture outcomes, cost-effectiveness, and the integration of bone health strategies into standard oncology care.

C. Jones¹, J. Michalek², E. Obomanu³, Y. Arya⁴, A. Syal⁵, S. Haddad¹, V. Kaklamani⁶, S. Shaikh⁶; ¹Hematology/Oncology, University of Texas Health Science Center San Antonio, San Antonio, TX, ²Population Health Sciences, University of Texas Health Science Center San Antonio, San Antonio, TX, ³Hematology/Oncology, Jefferson Einstein Hospital, Philadelphia, PA, ⁴Hematology/Oncology, Mayo Clinic Jacksonville, Jacksonville, FL, ⁵Hematology/Oncology, Mayo Clinic Jacksonville, San Antonio, FL, ⁶Hematology/Oncology, Mays Cancer Center, MD Anderson, San Antonio, TX.

Introduction: Endocrine therapy (ET) is central to treating hormone receptor-positive breast cancer (BC), but its side effects impact adherence and quality of life, especially in patients with metabolic dysfunction. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors offer cardiometabolic benefits, potentially improving inflammation, glycemic control, and physical well-being. However, data on SGLT-2 use in BC patients is scarce. This study is the first to evaluate the real-world effects of SGLT-2 inhibitors on all-cause mortality and ET tolerability in BC patients. Methodology: We conducted a real-world analysis using the TrinetX database, which includes data from 184 million patients in 156 healthcare organizations, to identify BC patients on ET (letrozole, anastrozole, exemestane, tamoxifen) who received SGLT-2 inhibitors vs. those who did not. Patients were grouped by age (≤50 and ≥51 years as a surrogate for menopausal status. Primary outcome: all-cause mortality from the start of the index event, defined as the first day meeting BC diagnosis and ET use, with or without SGLT-2. Secondary endpoint: ET tolerability. Propensity score matching completed by TriNetX adjusted for confounders. Multivariate analysis yielded odds ratios and risk differences with 95% CI. Results: Among 1,136 BC patients ≤50 years, 568 were assigned to each group (SGLT-2 vs non-SGLT-2). For patients ≥51 years (n=28,600), each group included 14,300. Demographics across cohorts were comparable. No mortality benefit was seen in premenopausal patients. In postmenopausal women, SGLT-2 use reduced all-cause mortality—647/13,676 events (SGLT-2) vs 953/13,517 (non-SGLT-2) [OR: 0.655 (0.591-0.726)]. In premenopausal patients, SGLT-2 reduced endometrial cancer risk [RD: -0.018 (-0.029, -0.007)] but increased diarrhea risk [OR: 2.305 (1.078, 4.930)]. No significant differences were found in hot flashes, PE, DVT, depression, osteoporosis, joint pain, fatigue, nausea/vomiting, abdominal pain, or dizziness. Among postmenopausal patients, SGLT-2 reduced PE [OR: 0.757 (0.605-0.948)] and osteoporosis [OR: 0.877 (0.784-0.981)], but increased risks of depression [OR: 1.153 (1.007-1.319)], nausea/vomiting [OR: 1.120 (1.001-1.253)], diarrhea [OR: 1.193 (1.058-1.345)], and dizziness [OR: 1.234 (1.103-1.380)]. No significant differences were found for hot flashes, DVT, EC, joint pain, fatigue, or abdominal pain. Conclusion: This analysis reveals novel evidence supporting the cardiometabolic potential of SGLT-2 inhibitors in hormone receptor-positive BC, particularly postmenopausal populations. These agents were linked to lower all-cause mortality and improved tolerance of specific ET-related effects. However, certain adverse risks require caution. Future prospective studies are essential to validate their role and safety in oncologic care.

T. Qian¹, X. Ye¹, Y. Wu², L. Pang¹, L. Li², X. Yu¹, Z. Wang¹, J. Huang¹; ¹Department of Breast Surgery, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, CHINA, ²Department of Medicial Oncology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, CHINA.

Background: Neoadjuvant chemotherapy (NAC) is the standard treatment for locally advanced breast cancer. Achieving a pathologic complete response (pCR) is strongly associated with favorable long-term outcomes. However, current imaging modalities, such as magnetic resonance imaging (MRI), have limitations in quantifying residual metabolic activity following NAC. Breast-specific gamma imaging (BSGI) provides functional assessment through the tumor-to-normal ratio (TNR), with established diagnostic value in prior studies. Prospective validation of TNR’s predictive value for pCR and survival outcomes is currently lacking. This study aims to evaluate whether post-NAC TNR can identify patients with chemo-sensitive tumors and a superior prognosis. Methods: This single-center prospective trial (NCT02556684) enrolled 137 patients with stage I-III breast cancer who received standard NAC followed by surgery between 2014 and 2023. Inclusion criteria required patients to have clinical stage T1-4 and N0-3, baseline biopsy-confirmed invasive carcinoma, and completion of the planned NAC regimen. Exclusion criteria were bilateral or metastatic disease or incomplete NAC. Breast-specific gamma imaging was performed after 2 cycles of NAC using 99mTc-sestamibi (MIBI) and dual-head gamma cameras. The tumor-to-normal ratio (TNR) was calculated as the maximum tumor uptake divided by the mean uptake in the contralateral breast parenchyma. The primary endpoints were pathological complete response (pCR) and 3-year disease-free survival (DFS). Statistical analyses included χ² tests for associations, Kaplan-Meier analysis with log-rank tests for survival comparisons, and multivariate Cox regression models adjusted for clinicopathologic covariates. Results: Baseline characteristics were balanced between groups for age, nodal status, grade, and Ki-67 (p>0.05), though TNR-low patients had significantly higher HER2+ subtype prevalence (65% vs. 46%, p=0.026). TNR-low was strongly associated with pathologic complete response (pCR), with 34.8% achieving pCR versus 14.7% in TNR-high group. Survival analysis demonstrated significantly improved disease-free survival (DFS) for TNR-low patients after median follow-up of 42.5 months. DFS benefits were consistently observed in the overall population and key clinical subgroups: overall cohort (hazard ratio [HR]=0.33, 95% confidence interval [CI]:0.14-0.81, p=0.002), HR+HER2- (HR=0.23; 95% CI:0.07-0.73; p=0.001), HER2+ (HR=0.23; 95% CI:0.04-1.48; p=0.009), pCR patients (HR=0, p=0.016), and non-pCR patients (HR=0.42; 95% CI:0.18-1.00; p=0.02). The triple-negative subgroup showed non-significant trends likely due to limited sample size (n=19). TNR demonstrated independent prognostic value in multivariate Cox regression. After adjusting for established factors (including pCR status, T stage, nodal stage, Grade and Ki-67 index), TNR-low status confirmed as a significant predictor of superior disease-free survival (DFS), with a hazard ratio of 0.43 (95% CI: 0.20-0.93; p=0.031). Notably, TNR demonstrated predictive capacity beyond pathologic complete response. No endpoint events occurred in TNR-low/pCR patients, whereas TNR-low/non-pCR patients had 58% lower risk of recurrence versus TNR-high/non-pCR patients. Conclusion: These results establish TNR as a robust imaging biomarker which serves as a valuable complement to current assessment methods. The prospective design and consistent survival benefit across multiple subgroups support clinical integration of BSGI-derived parameters to guide post-neoadjuvant risk stratification, potentially enabling therapy escalation for TNR-high/non-pCR patients and de-escalation strategies for TNR-low/pCR patients.

M. Diogenes¹, M. Antonini², A. Mattar¹, F. P. Cavalcante³, F. Zerwes⁴, F. Brenelli⁵, A. Frasson⁶, M. Eduardo⁷, G. Facina⁸, H. L. Couto⁹, S. Rondelo¹, R. Arakelian¹, V. Rocha¹⁰, L. Chrispim¹¹, M. Madeira¹², L. Gebrim¹³, L. Okumura¹⁴, P. Baruel¹⁴, R. Lopes²; ¹Mastology, Hospital da Mulher, São Paulo, BRAZIL, ²Mastology, Hospital do Servidor Público Estadual Francisco Morato de Oliveira, São Paulo, BRAZIL, ³Mastology, Hospital Geral de Fortaleza, Fortaleza, BRAZIL, ⁴Mastology, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, BRAZIL, ⁵Mastology, Universidade Estadual de Campinas, Campinas, BRAZIL, ⁶Mastology, Hospital Albert Einstein, São Paulo, BRAZIL, ⁷Mastology, Americas Oncologia, Rio de Janeiro, BRAZIL, ⁸Mastology, Universidade Federal de São Paulo, São Paulo, BRAZIL, ⁹Mastology, Redimama – Redimasto, Belo Horizonte, BRAZIL, ¹⁰Mastology, Universidade Nove de Julho, São Paulo, BRAZIL, ¹¹Mastology, Pérola Centro de Pesquisa em Oncologia, São Paulo, BRAZIL, ¹²Mastology, Faculdade Israelita de Ciências da Saúde Albert Einstein, São Paulo, BRAZIL, ¹³Mastology, Hospital Beneficiencia Portuguesa de São Paulo, São Paulo, BRAZIL, ¹⁴Statistics, Verde Health Care Consultancy, Curitiba, BRAZIL.

Background: accurate lymph node evaluation is essential for breast cancer staging, treatment planning and diagnosis of recurrent disease. Fine-needle aspiration (FNA) and core needle biopsy (CNB) are the two main percutaneous techniques used, but they differ in diagnostic yield, complication rates and associated healthcare costs. Objectives: to compare the diagnostic performance and economic impact of FNA versus CNB for lymph node evaluation in breast cancer patients within the Brazilian public healthcare system, emphasizing the relevance of cost-effective strategies in low- and middle-income countries (LMICs). Methods: a retrospective cohort study was conducted, including women with suspicious lymph nodes who underwent FNA or CNB between 2015 and 2023. A 1-year budget impact model nested with a decision tree model was used as economic model. Probabilities from the cohort study were used as clinical inputs. Costs were obtained from Sigtap (Brazilian listing of procedures reimbursement). The economic analysis considered only the procedural cots, assuming that each patient could undergo either FNA or CNB as the initial approach. In cases of inconclusive results, the patient could then undergo CNB or surgery. All analyses were reported as American dollar (USD), using an exchange rate of 6 brazilian reais to 1 USD. Results: the 300 women included in the study had similar ages (FNA: 53 vs CNB: 54 years old, average). The overall rate of inconclusive results in the sample was 15%. The rate of inconclusive results in procedures performed with CNB was lower than FNA (2.7% vs. 50.7%, p<0.05). Among the 79 patients who underwent FNA as the initial procedure, the total cost was USD 16,901, whereas for the 221 women who initially underwent CNB, the cost was USD 9,930. Although the initial FNA procedure was less expensive (USD 1,755) than the initial CNB procedure (USD 8,185), FNA resulted in a 17-fold higher rate of inconclusive results, and the need for additional procedures made CNB more cost-effective overall. A scenario in which only FNA was available as the initial procedure resulted in 11% higher overall costs compared to the base-case scenario (USD 26,832). Conversely, if CNB were available to all patients as the initial procedure, overall costs would be USD 13,718, approximately 50% lower than the base-case scenario. Conclusion: core needle biopsy offers superior diagnostic performance and greater economic efficiency compared to fine-needle aspiration for lymph node evaluation in breast cancer. Prioritizing CNB as the first-line diagnostic approach could improve resource allocation in public healthcare systems, particularly in LMICs where cost-effectiveness is crucial to expanding access to high-quality cancer care.

A. Michel¹, J. Zahlan², K. D. Crew¹; ¹Medical Oncology, Columbia University Irving Medical Center, New York, NY, ²Public Health, Columbia University Mailman School, New York, NY.

Introduction: Recent randomized controlled trials (RCTs) of breast MRI combined with mammography among high-risk women resulted in fewer interval breast cancer (BC) cases and earlier cancer detection compared to mammography alone. Despite this finding, supplemental breast MRI is underutilized. We aimed to identify factors associated with the receipt of supplemental breast MRI in a racially/ethnically diverse population of high-risk women.Methods: We conducted a retrospective cohort study among high-risk women undergoing screening mammography at Columbia University Irving Medical Center (CUIMC) in New York, NY, from 2007-2024. BC risk categories were classified based upon ICD-9/10 diagnostic codes or findings from breast radiology/pathology reports: 1) at high risk for BC, 2) family history of BC, 3) extremely dense breasts, 4) high-risk breast lesion (atypical hyperplasia [AH] or lobular carcinoma in situ [LCIS]), and 5) genetic predisposition for BC. Patients with a diagnosis of BC prior to 2007 were excluded. We collected information on demographic and clinical characteristics in the electronic health record (EHR), including age, race, ethnicity, primary health insurance, body mass index, mammographic density (BIRADS classification), benign breast biopsies, and family history of BC. Our primary outcome was receipt of supplemental breast MRI based upon radiology reports in the EHR. A multivariable logistic regression model was used to determine the association between breast MRI receipt and demographic and clinical characteristics.Results: Of the 54,122 women included in our analysis, the mean age was 58 years (SD, 10), including 29.0% non-Hispanic White women, 34.0% Hispanic, 12.0% non-Hispanic Black, 3.9% Asian, and 5.1% other or multiracial. In terms of BC risk factors, 4.5% of the women had extremely dense breasts, 16.0% had a family history of BC, 2.0% had AH or LCIS, and 1.6% had a genetic predisposition for BC. Overall, only 3.6% of women received a supplemental breast MRI. In multivariable analysis, younger age was significantly associated with breast MRI receipt, with women aged 25-34 demonstrating higher odds of undergoing supplemental breast MRI (odds ratio [OR]=2.59; 95% confidence interval [CI]=1.77-3.72) compared to those aged 45-54. Compared to non-Hispanic White women, Asian and Hispanic women had significantly lower odds of receiving a breast MRI (OR=0.72, 95% CI=0.63-0.82 and OR=0.66, 95% CI=0.51-0.84, respectively). Having extremely dense vs. less dense breasts on mammography (BIRADS D vs. B) was associated with higher breast MRI uptake (OR=1.99, 95% CI=1.35-2.92). Compared to women with a diagnostic code for at high risk for BC, those in other risk categories had significantly higher odds of receiving a screening breast MRI: family history of BC (OR=7.14, 95% CI=6.36-8.02), genetic predisposition to BC (OR=26.6, 95% CI=22.30-31.70), and high-risk breast lesions (OR=28.1, 95% CI=23.70-33.30). We did not observe differences in breast MRI use among Black vs. White women or based upon health insurance status (private vs. public).Conclusion: In a racially/ethnically diverse cohort of women at high risk for BC, only 3.6% received a supplemental breast MRI. Utilization varied significantly by age, race/ethnicity, and specific BC risk factors. These findings highlight persistent gaps in the uptake of guideline-concordant supplemental BC screening. We plan to study the impact of breast MRI use on early detection of local disease and screen-detected vs. interval BC. Future research should investigate patient-, provider- and system-level barriers to adoption of supplemental breast MRI among high-risk women to promote equitable access to advanced screening modalities.

S. Liu¹, Y. Zhang², Y. Yang², D. Zhai¹, X. Kuang¹, Y. Shi¹, L. Yu¹, Y. Zhang¹, N. Shao¹, X. Zhang², Y. Lin¹; ¹Breast Disease Center, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, CHINA, ²Department of Nuclear Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, CHINA.

Objectives and rationale: Early response prediction during neoadjuvant therapy (NAT) for breast cancer (BC) enables response-guided precision treatment. Imaging-based post-NAT evaluation may reduce dependence on pathological complete response (pCR) confirmation and facilitate surgical de-escalation. Fibroblast activation protein inhibitor (FAPI) PET/MRI represents a promising molecular imaging modality targeting the tumor microenvironment. This study aimed to evaluate the efficacy of ¹⁸F-FAPI-42 PET/MRI for early and late prediction of pCR to NAT in BC. Methods: 45 consecutive patients with newly diagnosed BC who met the criteria for NAT were prospectively enrolled and underwent ¹⁸F-FAPI-42 PET/MRI before treatment initiation (PET1), after two cycles of NAT (PET2), and before post-NAT surgery (PET3). SUVmax was measured in the primary tumor and metastatic lymph nodes (MLNs). The tumor-to-background ratio (TBR) was calculated as the lesion SUVmax divided by the SUVmean of contralateral normal breast tissue. The percentage changes in SUVmax and TBR from baseline were calculated after 2 NAT cycles (ΔSUVmax1 and ΔTBR1) and before surgery (ΔSUVmax2 and ΔTBR2). Predictive performance of ¹⁸F-FAPI uptake was analyzed by receiver operating characteristic curve analysis and the area under the curve (AUC). The Youden index determined optimal cutoffs. Results: 18 patients (40%) achieved pCR, while 27 patients (60%) exhibited residual disease. Among 40 patients with MLNs, 16 (40%) attained axillary pCR. By molecular subtypes, pCR rates were 21.1% (4/19) in HR-positive/HER2-negative, 52.4% (11/21) in HER2-enriched, and 60.0% (3/5) in TNBC cases. The ΔSUVmax of primary tumors (r = 0.636; P < 0.001) and MLNs (r = 0.560; P < 0.001) were significantly correlated between PET2 and PET3. Patients achieving pCR demonstrated significantly lower absolute SUVmax and TBR values at both PET2 and PET3 compared to non-pCR cases (P < 0.05). Furthermore, greater reductions in both SUVmax and TBR at any time point were strongly associated with pCR (P < 0.05). In predicting pCR, the ΔSUVmax1 (AUC = 0.792; sensitivity = 55.6%; specificity = 92.6%) and ΔTBR1 (AUC = 0.774; sensitivity = 61.1%; specificity = 100%) of the primary tumor had the highest specificity; the TBR3 (AUC = 0.855; sensitivity = 94.1%; specificity = 76.0%) and ΔTBR2 (AUC = 0.815; sensitivity = 94.1%; specificity = 72.0%) of the primary tumor showed the highest sensitivity. In the HR-positive/HER2-negative subtype, parameters derived from PET2 (SUVmax2 and TBR2; AUC = 0.950; sensitivity = 100%; specificity = 86.7%) and all parameters derived from PET3 (SUVmax3, ΔSUVmax2, TBR3, and ΔTBR2; AUC = 1.000; sensitivity = 100%; specificity = 100%) of the primary tumor showed optimal AUC in predicting pCR; both the ΔSUVmax1 and ΔSUVmax2 of MLNs achieved 100% sensitivity for axillary pCR prediction. Conclusions: Early-phase ¹⁸F-FAPI-42 PET/MRI demonstrates high specificity in predicting pCR, which may facilitate the selection of alternative NAT regimens for non-pCR cases. Preoperative ¹⁸F-FAPI-42 PET/MRI shows high sensitivity for pCR prediction, which can identify potential candidates for surgery de-escalation. ¹⁸F-FAPI-42 PET/MRI exhibits excellent potential for both early and late-phase prediction of pathological response to NAT in HR-positive/HER2-negative BC.

T. Hojo¹, N. Masuda², H. Iwata³, A. Yoshimura⁴, T. Ueno⁵, M. Tsuneizumi⁶, T. Onishi⁷, H. Matsumoto⁸, Y. Yanagita⁹, M. Sawaki¹⁰, H. Kawabata¹¹, S. Takayama¹², H. Shigematsu¹³, T. Fujisawa⁹, F. Hara⁴, R. Kajikawa¹⁴, K. Sasaki¹⁵, T. Shien¹⁶; ¹Department of Breast Care, Saitama Medical Center, kawagoeshi, JAPAN, ²Department of Breast Surgery, Kyoto University,, Sakyo-ku, JAPAN, ³Department of Advanced Clinical Research and Development, Nagoya City University Graduate School of Medical Sciences, Nagoya, JAPAN, ⁴Department of Breast Oncology, Aichi Cancer Center, Nagoya, JAPAN, ⁵Department of Breast Center, Breast Oncology Center, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto, JAPAN, ⁶Department of Breast Surgery, Shizuoka General Hospital, Shizuoka City, JAPAN, ⁷Department of Breast Surgery, National Cancer Center Hospital East, Kashiwa, JAPAN, ⁸Department of Breast Surgery, Saitama Cancer Center, Kitaadachi-gun, JAPAN, ⁹Department of Breast Oncology, Gunma Prefecture Cancer Center, Ota, JAPAN, ¹⁰Department of Breast Surgery, NHO Nagoya Medical Center, Naka-ku, JAPAN, ¹¹Department of Breast and Endocrine Surgery, Toranomon Hospital, Minato-ku, JAPAN, ¹²Department of Breast Surgery, National Cancer Center Hospital, Chuo-ku, JAPAN, ¹³Department of Breast Surgery, Hiroshima University Hospital, Minami-ku, JAPAN, ¹⁴Department of JCOG Operations Offic, Data Center, Chuo-ku, JAPAN, ¹⁵Department of JCOG Operations Office, Data Center, Chuo-ku, JAPAN, ¹⁶Department of Breast and Endocrine Surgery, Okayama University Hospital, Kitaku, JAPAN.

Background: For postoperative follow-up of breast cancer, only annual MMG is recommended, commonly in guidelines around the world. Early detection of metastasis and recurrence has been considered of little significance. However, there have been remarkable advances in the development of new drugs, and with the improved accuracy of imaging tests for early detection and recent innovations in MRD assay technology, the importance of early detection of metastasis and recurrence in other cancer tumors is being emphasized. Methods: The INSPIRE trial (Intensive follow (IF) vs. standard follow (SF) post-operative surveillance in high-risk breast cancer patients; JCOG1204) is a randomized phase III study due to confirm the superiority of IF in terms of overall survival (OS) in high-risk breast cancer patients after radical surgery. Eligible participants were from 20 to 70 years old and had undergone radical breast and axillary surgery. Patients were randomized 1:1 to the SF arm (annual MMG and tumor markers) or the IF arm (annual MMG, whole-body CT or PET/CT every 6 months until 3 years and every 12 months until 5 years after surgery, and tumor marker every 3 months until 3 years and 6 months until 5 years after surgery). Adjustment factors: ER and HER2 status, with/without preoperative chemotherapy, institutions. Primary endpoint: OS. Key secondary endpoints: disease free survival, relapse-free survival (RFS), distant metastasis-free survival (DMFS). Five-year follow-up was completed for all enrolled patients. Data cut-off is Jan.2025.Results: From Nov 2013 to Jan 2020, 1034 pts were enrolled. 516 and 518 were assigned to SF and IF, respectively. Median follow up time is 82.9 (range: 0.5-130.9) months. The patient’s characteristics were well balanced between two arms: median age 53 (range: 23-70) years, PS 0/1:1018/16, pre/post menopause: 486/548, median tumor size: 3.0 (range:0-23 cm), stage 1A/2A/2B/3A/3B/3C: 78/262/346/153/83/110, ER+/-: 617/417, HER2+/-: 218/816, preoperative chemo +/-: 596/438, 7Y RFS: 73.0% vs 73.6% in SF and IF arm, respectively (p=0.999, 95% confidence interval [CI]:0.79-1.26). 7Y DMFS: 74.1% vs 75.5% in SF and IF arm, respectively (p=0.974, 95% CI: 0.76-1.24). The duration to recurrence/distant recurrence is 29.3/31.7 and 24.0/24.1 months in SF and IF, respectively. Lead times (the difference between SF and IF) of all and each subtype are shown in Table.Conclusion: There was no significant difference in RFS/DMFS between IF and SF arm. Recurrence was detected earlier by IF compared to SF, and the median time to recurrence was longer in luminal type than in TN type. However, the lead times were similar. The results of continued follow-up are awaited to see if this will lead to an improvement in overall survival, which is the primary endpoint.

S. Loubrie¹, J. Lim², S. Batasin¹, H. J. Yu¹, J. Zou³, S. Ebrahimi¹, C. C. Conlin¹, A. Guidon⁴, T. M. Seibert⁵, A. M. Dale⁶, A. Wallace⁷, H. Ojeda-Fournier¹, A. E. Rodriguez-Soto¹, R. Rakow-Penner⁸; ¹Radiology, UC San Diego, La Jolla, CA, ²Radiology, Hallym University Dongtan Sacred Heart Hospital, Hwaseong-si, KOREA, REPUBLIC OF, ³Herbert Werteim School of Public Health and Human Longevity Science, UC San Diego, La Jolla, CA, ⁴Global MR and Workflow, GE Healthcare, Boston, MA, ⁵Radiology, Bioengineering & Radiation oncology, UC San Diego, La Jolla, CA, ⁶Radiology & Neurosciences, UC San Diego, La Jolla, CA, ⁷Surgery, UC San Diego, La Jolla, CA, ⁸Radiology & Bioengineering, UC San Diego, La Jolla, CA.

Problem: Breast MRI is recommended annually for high-risk individuals, typically using dynamic contrast-enhanced (DCE) MRI, which requires intravenous gadolinium. However, the added cost and invasiveness limit its use in average-risk populations. Developing a non-contrast MRI method would allow for expansion to broader screening. Diffusion-weighted imaging (DWI), a non-contrast technique, holds promise but suffers from low spatial resolution, limiting detection of small lesions. Restriction Spectrum Imaging (RSI), which uses multi-shell DWI, separates signal into restricted, hindered, free, and flow components without exogenous contrast, and has shown improved lesion characterization. This abstract presents a novel RSI model using multi-b-value input and high-resolution multi-band (MB) acquisition, achieving 2 mm isotropic resolution and improving small lesion detectability. Methods: Along with standard clinical DWI and DCE, high-resolution multi-shell (b-values (# of directions) 0 (1), 100 (6), 800 (6), 1500 (6), 3000 (12) s/mm²) DWI was collected using MB on 122 breast cancer and screening patients. RSI models follow a multi-exponential formula: S(b)= S₀Σexp(-b*ADC_i)=ΣC_iexp(-b*ADC_i). Tri- and tetra-exponential models (3C- and 4C-RSI) ADC_i (fixed compartment apparent diffusion coefficients) were first calculated on large cancers (largest dimension > 2cm – 61 cancers). C_i signal contribution maps (C-maps) were estimated and provided spatial representation of each diffusion component. The products C₁C₂ and C₂C₃ were calculated as well. ADC maps from clinical DWI and DCE subtraction images (peak enhancement – pre-phase) were computed. To assess lesion conspicuity, contrast-to-noise ratios (CNR) were measured in C-maps on 28 lesions from a subset of 22 patients and compared to CNR from ADC and DCE. Finally, receiver operating characteristic (ROC) curves of each model and ADC were measured on the subset, separating malignant from benign lesions, by fitting a generalized linear model. Results: RSI models’ separation of diffusion contents are summarized on Table 1. Regarding CNR, 3C-RSI showed highest values in C₁C₂ (median: 3.42, IQR: 2.66) and C₂C₃ (2.72, 1.72). For 4C-RSI, C₁C₂ (3.15, 3.42) and C₂C₃ (3.66, 3.79) were also highest. DCE had the highest (3.86, 1.45) and ADC the lowest (1.29, 0.49). Of the 28 test lesions (median lesion size: 2 cm, min: 5 mm, max: 7 cm – largest dimension), 7 were benign. ADC had an AUC of 0.78 while 3C- and 4C-RSI had an AUC of 0.87 and 0.96 respectively. DCE is considered 100% sensitive as selected lesions are based on DCE findings and had a specificity of 75% (7 lesions are benign), while at 80% sensitivity ADC, 3C- and 4C-RSI had a specificity of 50, 83 and 100%, respectively. Conclusion: RSI models achieved comparable CNR to DCE, outperforming ADC. They also had the highest AUCs and specificities, highlighting RSI as a potential non-contrast method for early detection.

M. T. K. Vithanage¹, S. H. Ekanayake¹, H. Ghimire¹, M. K. Dayananda², G. Qin³, R. Aneja⁴, E. A. Janssen⁵, A. G. Unil Perera¹; ¹Department of Physics and Astronomy, Georgia state University, Atlanta, GA, ²Department of Physics, Georgia state University Perimeter College, Dunwoody, GA, ³Department of Mathematics and Statistic, Georgia state University, Atlanta, GA, ⁴School of Health Professions, University of Alabama at Birmingham, Birmingham, AL, ⁵Department of Pathology, Stavanger University Hospital, Stavanger, NORWAY.

Attenuated Total Reflection Fourier-Transform Infrared (ATR-FTIR) spectroscopy offers a promising, minimally invasive, and label-free approach for serum analysis, capable of detecting molecular-level changes associated with breast cancer (BC). Few studies have examined the use of Infrared (IR) spectroscopy to monitor BC progression, and correlations between specific spectral changes and tumor development remain underexplored. This study provides results from a technique that uses ATR-FTIR spectroscopy of blood serum, combined with curve fitting analysis to identify molecular changes in five spectral biomarkers (SBMs) linked with BC progression across tumor stages. These include increases in β-sheet structures (1536 cm⁻¹) and disordered protein structures (1558 cm⁻¹), and a decrease in α-helix (1547 cm⁻¹), PO₂⁻ asymmetric stretching (1062 cm⁻¹), and C-O stretching of glycogen (1050 cm⁻¹). These SBMs showed statistically significant differences (p < 0.05 to p < 0.0001) between healthy controls (HC) and also between different BC Groups classified by tumor size. Among them, the β-sheet (1536 cm⁻¹), α-helix (1547 cm⁻¹), and PO₂⁻ asymmetric stretch (1062 cm⁻¹) SBMs demonstrated high diagnostic performance, each achieving 93% sensitivity and 100% specificity. These findings highlight utility of specific SBMs for monitoring BC and suggest that IR-spectroscopy in combination with curve fitting technique could serve as a robust approach for differentiating BC severity levels based on tumor size.

A. Keller, M. Elezaby, L. Salkowski, R. Strigel, A. Fowler; Department of Radiology, University of Wisconsin School of Medicine and Public Health, Madison, WI.

Purpose: To evaluate abnormal interpretation/recall rates, imaging findings, and outcomes for asymptomatic lactating women at elevated lifetime risk of breast cancer screened with mammography (MG) and/or breast MRI. Methods: An IRB-approved, HIPAA-compliant retrospective chart review was conducted at a tertiary academic center (2013-2024). Patients were included if lactating and undergoing breast cancer screening due to a personal history of breast cancer, strong family history, or hereditary breast cancer predisposition. Screening was performed with MG, MRI, or both during lactation. Imaging findings were defined using American College of Radiology Breast Imaging Reporting and Data System (BI-RADS 5th ed.). Final outcomes were verified via histopathology or ≥2 years of clinical/imaging follow-up; patients without this were excluded. Results: Of 118 patients identified, 9 were excluded for insufficient follow-up. Among 109 included patients, 63 underwent MG (58 with tomosynthesis), and 45 had MRI. Mean age was 37 ± 4 years (range 27–47) for the MG group and 34 ± 3 years (range 26–43) for the MRI group. Overall, 84% had a first-degree family history of breast cancer, 13% were BRCA2+, 9% BRCA1+, and 8% had a prior breast cancer diagnosis. In the MG group, 30% were baseline screening exams and 70% were subsequent screening exams. Breast density was 54% extremely dense and 48% heterogeneously dense. BI-RADS assessments included 41 BI-RADS 1 (negative) and 16 BI-RADS 2 (benign). The recall rate was 9% (n=6), based on BI-RADS 0 assessments, for an asymmetry (n=1), mass (n=2), calcifications (n=2), and possible architectural distortion (n=1). Diagnostic imaging for the recalled cases yielded 4 benign/negative results, 1 BI-RADS 4A mass confirmed as fibroadenoma on US-guided biopsy, and 1 BI-RADS 3 finding with stable calcifications on follow-up imaging. In the MRI group, 40% were baseline screening exams and 60% were subsequent screening exams. Breast composition was 67% extremely dense and 29% heterogeneously dense. Background parenchymal enhancement (BPE) was marked in 62%, moderate in 16%, and mild/minimal in 22%. BI-RADS assessments were 41 BI-RADS 1 and 16 BI-RADS 2. The abnormal interpretation rate was 9% (n=4). Both BI-RADS 0 cases showed axillary lymphadenopathy: US was benign (BI-RADS 2) in one and suspicious (BI-RADS 4) in the other (biopsy-confirmed benign lymph node). One BI-RADS 4A case (focal non-mass enhancement) was benign breast tissue with dense stromal fibrosis on histopathology from MRI-guided biopsy. The other BI-RADS 4A case (mass) was benign lactational changes in accessory axillary tissue on histopathology from US-guided biopsy. No cancers were detected. Conclusion: Screening recall and abnormal interpretation rates were low in both the MG and MRI groups and fell within the acceptable range for screening MG performance (5-12%). Although no pregnancy-associated cancers were diagnosed, findings support continued adherence to high-risk screening during lactation. Screening high-risk lactating patients is potentially challenging due to physiologic changes in breast density and BPE which can cause false-positive and false-negative results. This study demonstrates that screening MG and breast MRI are practical tools in the high-risk lactating population.

N. Onishi¹, R. Mukhtar², T. Hope¹, P. Metanat¹, Y. Wang¹, B. Joe¹, K. Ray¹, S. Choi², L. Awni¹, D. Heditsian³, D. Romer³, S. Brain³, I-SPY 2 Imaging Working Group, I-SPY 2 Investigator Network, J. Chien⁴, L. Esserman², N. Hylton¹; ¹Department of Radiology & Biomedical Imaging, University of California, San Francisco, San Francisco, CA, ²Department of Surgery, University of California, San Francisco, San Francisco, CA, ³I-SPY 2, Breast Cancer Advocacy Group, San Francisco, CA, ⁴Department of Medicine, University of California, San Francisco, San Francisco, CA.

Background Dedicated breast positron emission tomography (dbPET) is an innovative imaging technology specially designed to scan only the breasts, providing high spatial resolution and detailed characterization of tumor uptake levels, distribution, and textures. Fibroblast activation protein (FAP), predominantly expressed in cancer-associated fibroblasts within the tumor stroma, has recently gained significant attention as a promising target for cancer diagnostics and therapy. Recent whole-body PET/CT studies reported that novel FAP-targeted radiotracers showed higher sensitivity in the detection of primary and metastatic invasive breast cancer compared to the standard ¹⁸F-fluorodeoxyglucose (FDG) radiotracer. FAP-targeted radiotracers may offer unique advantages in depicting primary breast cancers, especially in invasive lobular carcinoma (ILC), which has unique imaging challenges due to its diffuse growth pattern and low cellularity. We present initial studies of FAP-targeted dbPET performed on the same day following whole-body PET/CT in patients with primary ILC lesions. Methods Patients with primary ILC were recruited from the participants of the Endocrine Optimization Program (EOP), a sub study of the I-SPY 2 TRIAL. After undergoing whole-body PET/CT with FAP-targeted radiotracer (6mCi +/-20% of ⁶⁸Ga-FAP-2286) on a separate research protocol, they underwent dedicated breast imaging using the MAMMI dbPET scanner (OncoVision, Spain) without additional radiotracer injection. Due to the transportation of patients between two different PET scanner locations, the average interval between radiotracer injection and the start of dbPET scanning was approximately 2.5 hours. The dbPET scans were performed in the prone position, starting with the ipsilateral breast followed by the contralateral breast, with each scan taking approximately 15 minutes per breast. FAP-dbPET images were interpreted alongside DCE-MRI scans obtained closest to the FAP-dbPET scans. Results Four patients with primary ILC have underwent FAP-dbPET scanning to date: #1. 59 year old postmenopausal woman with Lt. ILC before treatment initiation #2. 78 year old postmenopausal woman with Rt. ILC before treatment initiation #3. 39 year old premenopausal woman with Lt. ILC after 4 weeks of neoadjuvant endocrine treatment #4. 51 year old premenopausal woman with bilateral ILC after 7 weeks of neoadjuvant endocrine treatment In all cases, known ILC lesions were clearly depicted on the dbPET as well as on the whole-bodyPET. Notably, for two patients, FAP-dbPET identified additional suspicious lesions with high uptake (pathology not confirmed) that were either uncertain or masked by background parenchymal enhancement in the DCE-MRI images. For individual patients, FAP-targeted dbPET will be presented along with whole-body PET/CT and DCE-MRI. Discussion Our preliminary study shows the promising capability of FAP-dbPET in visualizing tracer uptake of primary ILC with high resolution. These scans may provide better visibility of ILC lesions and provide a more accurate way to assess response to neoadjuvant treatment. In combination with novel tracers such as FAP that may provide unique insight into the biology of primary breast tumors and drug mechanism of action, dbPET provides a cost-effective and clinically-feasibly technology that will facilitate use of PET biomarkers in clinical trials testing novel drugs in the neoadjuvant setting. Based on these preliminary results, we plan to expand our FAP-dbPET study with advanced qualitative and quantitative analyses, over time, to better measure response to therapy and ultimately to help evaluate how best to target therapy in the setting of lobular cancer.

L. Schwartzberg¹, M. Karimzadeh², A. Momen-Roknabadi², T. B. Cavazos², N. Chen³, J. Wang³, M. Multhaup², J. Ku², A. Krishnan⁴, M. Hernandez⁴, R. Hanna⁴, L. Fish⁵, M. Gebala⁴, H. Goodarzi², H. Li³, F. Hormozdiari², B. Behsaz³, A. Hartwig⁴, B. Alipanahi²; ¹Pennington Cancer Institute, Reno Health, Reno, NV, ²Computational Biology and Algorithms, Exai Bio Inc., Palo Alto, CA, ³Engineering, Exai Bio Inc., Palo Alto, CA, ⁴Assay Development, Exai Bio Inc., Palo Alto, CA, ⁵Research and Early Development, Exai Bio Inc., Palo Alto, CA.

Background. Early detection of breast cancer saves lives, yet mammography—the current standard for screening—has well-documented limitations. Its sensitivity is notably reduced in women with dense breast tissue, where tumor tissue may be obscured by the naturally dense parenchyma, leading to false-negative findings. Emerging blood-based biomarkers for early cancer detection and monitoring have the potential to augment existing image-based screening technologies in high-risk populations including dense breasts. Tumor-derived RNA has two key advantages compared to tumor-derived DNA which favor its application in diagnosis of small tumors; i) each cell can produce multiple copies of RNA, while DNA content is limited to cellular ploidy, and ii) while cfDNA can originate from any genomic region, cfRNA can only originate from the subset of accessible chromatin undergoing active transcription. We have previously identified and developed a novel category of cancer-associated, small orphan non-coding RNAs (oncRNAs), and combined them with generative AI modeling to develop a liquid biopsy platform requiring a small volume of plasma. This platform has demonstrated high sensitivity and specificity for detection of early stage disease across several cancer types. Here we developed a cell-free RNA and AI-based assay to detect breast cancer across the range of tumor stages and sizes and analyzed it in a separate, independent test set. Methods. We utilized The Cancer Genome Atlas (TCGA) small RNA profiles to discover a library of pan-cancer oncRNAs that were significantly enriched among breast tumors compared to adjacent normal tissues. Our plasma-based training cohort comprised of 745 female patients with clinically diagnosed, pathologically confirmed untreated breast cancer and 258 age-matched women with no known history of cancer from five different sources (mean age 59.3 years ± 13.4 S.D.), including 593 stage I/II (79.6%), 147 stage III/IV (19.7%), and 5 unknown stage (0.7%) patients. The test set was obtained from a different sample source and consisted of blood samples from 92 female patients with breast cancer and 98 individuals with no known diagnosis of cancer (mean age 60 years ± 10.8 S.D.). The test-set included 60 stage I/II (65.22%) and 32 stage III/IV (34.78%) patients. We processed 1 mL of plasma for each sample through our universal, automated cell-free RNA workflow and sequenced at an average depth of 53 million ± 20 S.D. 100 bp single-end reads. We trained a generative AI model using 5-fold cross-validation (CV) to predict presence or absence of invasive cancer and then applied it on the independent test set. Results. Our model achieved an overall AUC of 0.88 (95% CI: 0.85-0.9) for predicting breast cancer versus controls in CV, and an overall AUC of 0.89 (0.83-0.93) in the independent test set. At 90% specificity, the model achieved overall cross-validated sensitivity of 71.8% (63.7%-77.6%) in the training data, and sensitivity of 71.7% (37.4%-79.5%) in the test set. For stage I breast cancer, the model had a CV sensitivity of 63% (57%-68%) in the training data, and 63% (44%-80%) in the test set, both at a 90% specificity. Conclusions. In an independent cohort, the oncRNA and AI-based plasma assay demonstrated high sensitivity for detecting early-stage invasive breast cancer. Given that 40-50% of women have dense breast tissue—where traditional imaging methods are less effective—and assay sensitivity of >70% in an independent cohort, our findings support the potential of oncRNA-based liquid biopsies for screening high-risk populations after negative mammography. A non-invasive blood test could complement current standard screening methodologies in women with dense breasts by stratifying women needing supplemental screening. A prospective study is planned to further validate these findings.

N. Komatsu¹, T. Takahara², H. Yano¹, M. Matsuyanagi¹, M. Oshi³, H. Ideguchi⁴, K. Taruno⁵, N. Hayashi⁵, T. Chishima¹; ¹Breast Surgery, Showa Medical University Northern Yokohama Hospital, Yokohama City, JAPAN, ²Radiology, Takahara Clinic – Innovative Scan, Tokyo, JAPAN, ³Breast Surgery, Yokohama City University Graduate School of Medicine, Yokohama City, JAPAN, ⁴Diagnostic Imaging, Kohoku NT Clinic, Yokohama City, JAPAN, ⁵Breast Surgical Oncology, Showa Medical University School of Medicine, Tokyo, JAPAN.

Background and Objectives: Diffusion-weighted whole-body imaging with background suppression (DWIBS) is a non-contrast MRI technique that visualizes the diffusion of water molecules while suppressing background signals, enabling the detection of malignant lesions. Due to its non-invasive nature and absence of radiation exposure, DWIBS has recently attracted increasing attention as a promising modality for breast cancer screening in Japan.Notably, no Japanese population-based data have demonstrated a mortality reduction from mammographic screening, and the utility of mammography remains a subject of debate, especially given that over 50% of Japanese women have heterogeneously or extremely dense breasts.This study aimed to assess the potential role of DWIBS as an alternative screening tool for breast cancer. Methods: We retrospectively analyzed 710 women who underwent DWIBS-based breast cancer screening at a dedicated MRI screening clinic in Yokohama, Japan, between April 2022 and January 2025. For those referred for further evaluation, clinical and mammographic data, including BI-RADS classification and breast density, were reviewed. DWIBS screening in this study was conducted as a self-paid service at a dedicated MRI screening clinic equipped with advanced diffusion-weighted imaging protocols. All scans were interpreted by radiologists with expertise in breast MRI. Results: Among the 710 women screened by DWIBS, 41 were referred for further evaluation (recall rate: 5.77%; national average for population-based mammographic screening in Japan: 8.4%). Of these, 30 underwent diagnostic work-up (follow-up rate: 73.2%; national average: 90.1%). Breast cancer was diagnosed in 7 individuals, yielding a cancer detection rate (CDR) of 0.99% (national average: 0.33%) and a positive predictive value (PPV) of 17.1% (national average: 5.4%).The median age of those requiring further evaluation was 46.5 years, with 18 of the 41 individuals (43.9%) under the age of 40, which is below the starting age for population-based breast cancer screening in Japan. Among the 7 diagnosed cases, 5 had a family history of breast or ovarian cancer in second-degree relatives, and 2 were under 40 years old with no prior history of mammography.Notably, 3 of the 7 confirmed cancer cases had BI-RADS 1 findings on mammography, indicating false-negative results. In addition, 5 individuals had extremely dense or heterogeneously dense breast tissue. Among the 11 individuals who did not undergo diagnostic follow-up despite referral, potential contributing factors included scheduling challenges, financial constraints, or limited awareness of the need for further evaluation. However, these factors were not formally investigated. Conclusion: DWIBS demonstrated a higher CDR and PPV than mammography and, with additional advantages such as being radiation-free, painless, and free from embarrassment, may serve as a promising tool for breast cancer detection, including among women at high risk or with dense breast tissue. To fully realize its potential as a screening modality, strategies to ensure diagnostic follow-up and further prospective validation are warranted.

A. Tanaka¹, A. Nguyen¹, M. D. Pegram², M. Khonkhodzhaev³, S. Shcherbakov⁴, D. Hoffman⁵, A. Lazarev⁶, B. Aram¹, T. J. Lomis⁷, P. Chawla⁸, L. Mourokh³, P. Lazarev⁶; ¹Clinical Operations and Development at EosDx, Inc., EosDx, Inc., Van Nuys, CA, ²Stanford Cancer Institute, Stanford University, Stanford, CA, ³Physics Department, Queens College of the City University of New York, New York, NY, ⁴Data Analytics Department, Matur UK Ltd., EosDx, Inc., Van Nuys, CA, ⁵Surgery, Daryl Hoffman Plastic Surgery, Campbell, CA, ⁶Software and Hardware Development, EosDx, Inc., Van Nuys, CA, ⁷Surgery, San Fernando Valley Cancer Foundation, Van Nuys, CA, ⁸Valley Breast Care Radiology, EosDx, Inc., Van Nuys, CA.