Poster Session 2

J. Kang, S. Jung, Y. Yoon, J. Oh, H. Koh, H. Shin, E. Kim, K. Yoon; Surgery, Seoul national university bundang hospital, Seongnam, KOREA, REPUBLIC OF.

Preoperative Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios as Predictors of Capsular Contracture after Nipple-Sparing Mastectomy with Implant-Based Breast Reconstruction Jongwon Kang¹, Sungjin Jung¹, Yena Yoon¹, Jeong-Hun Oh¹, Hyoung Won Koh¹, Kyung-Hwak Yoon¹, Hee-Chul Shin¹, Eun-Kyu Kim*¹ ¹Department of Surgery, Seoul National University College of Medicine, Breast Care Center, Seoul National University Bundang Hospital, Korea BackgroundCapsular contracture is a major complication following nipple-sparing mastectomy (NSM) with direct-to-implant (DTI) breast reconstruction. While inflammation is a known contributor to capsular contracture, the role of systemic inflammatory markers such as the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) remains unclear. This study aimed to evaluate their predictive value for capsular contracture.MethodsWe retrospectively reviewed 376 patients who underwent NSM with immediate DTI reconstruction. Patients were grouped by Baker’s classification into the non-contracture (grades 1–2) and the contracture (grades 3–4) groups. Clinical and pathological factors including preoperative NLR and PLR were analyzed. The optimal cut-off values for NLR and PLR were determined using receiver operating characteristic (ROC) curve analysis.ResultsAmong the 376 patients, 43 (11.4%) developed grade 3 or 4 capsular contracture during follow-up. The contracture group showed significantly higher rates of radiotherapy, chemotherapy, and elevated NLR/PLR. Multivariate analysis identified radiotherapy (OR 12.142, p<0.001) and elevated NLR and PLR (OR 5.287, p=0.001) as independent risk factors of capsular contracture. In subgroup analysis, NLR and PLR were not significant predictors among patients who did not receive radiotherapy, but remained significant among those who received radiotherapy (OR 7.334, p=0.002).ConclusionElevated NLR and PLR are associated with an increased risk of capsular contracture in patients undergoing NSM with DTI reconstruction, particularly in patients receiving radiotherapy. These findings suggest that systemic inflammation and radiation-induced fibrosis may contribute synergistically to capsular contracture development. As these markers are routinely available, they may serve as useful tools for preoperative risk stratification and individualized patient counseling in reconstructive breast surgery. Key wordsBreast cancer, Nipple sparing mastectomy, Direct-to-implant reconstruction, Capsular contracture, Systemic inflammation, Neutrophil-to-lymphocyte ratio, Platelet-to-lymphocyte ratio, Radiation therapy

D. Hequet¹, A. Hababou², G. Aubry¹, R. Salmon³, S. Harguem², M. Bou Antoun², J. Seror¹; ¹Surgery, Institut Bourdonnais, Paris, FRANCE, ²Radiology, Groupe Union Imagerie, Paris, FRANCE, ³Surgery, Clinique Saint Jean de Dieu, Paris, FRANCE.

Introduction: Preoperative localization of non-palpable breast lesions, whether performed the day before or on the day of surgery, can be anxiety-inducing for patients. The scheduling in a busy operating theater for short procedures is highly sensitive to even minor delays. Localization appointments may cause such delays, as well as raise potential timing confusions between surgery time, arrival time at the care center, and localization time. Moreover, wire-guided localization requires specific radiology sessions and coordination with radiologists specialized in breast imaging. For these reasons, we progressively implemented preoperative localization using a magnetic clip. Placement is done a few days before surgery, which also allows a comprehensive re-review of the radiologic images. The objective is to describe the organizational impact and the re-excision rate of the systematic use of magnetic seeds in a single institution.Methods: Retrospective single-center study. We describe the characteristics of cases with magnetic seed localization and compare these features, as well as ambulatory stay durations, to a historical control group that underwent wire-guided localization. For this comparison, only consecutive patients who had unifocal, unilateral breast cancer and were treated on an outpatient basis were included.Results: Between March 2024 and June 2025, 261 patients were referred to the radiology department for magnetic seed placement before surgery. During imaging review, additional lesions were detected in 21 patients (8%), leading to total mastectomy in 5 cases. Excluding 8 patients (3%) who were scheduled for inpatient admission, 232 underwent magnetic seed placement, including 35 (15%) for benign lesions. We compared 197 patients who had magnetic seed localization for cancer between March 2024 and June 2025 to 60 patients in the historical control group who underwent wire localization for cancer between November and December 2023. The median age in both groups was 62 years (p = 0.98). The control group had a higher proportion of in situ ductal carcinoma (n = 18, 30% vs. n = 27, 15%, p = 0.02), while the magnetic seed group underwent more axillary procedures (n = 170, 86% vs. n = 42, 70%, p = 0.009). Tumor size was slightly larger in the magnetic seed group (10 mm vs. 8 mm, p = 0.04). Fewer re-excisions for positive margins occurred in the magnetic seed group (n = 3, 1.5% vs. n = 8, 13%, p < 0.01). This result was confirmed in multivariate analysis : use of magnetic seed reduced independently the rate of re-excision with an OR of 0.37 (IC95%[0.002-0.001], p=0,0018). Operating time was equivalent in both groups (32 min vs. 33 min, p = 0.87), but ambulatory stay was reduced by more than 2 hours in the magnetic seed group (5h 14 vs. 7h 19, p < 0.01).Conclusion: The use of magnetic seeds enables time savings on the day of surgery, streamlining the operating theater schedule and reducing patient anxiety associated with pre-surgical delays. Re-excision rates is dramatically decreased when using magnetic seeds.

L. Almaghrabi¹, J. Alazhri², F. Aldulaijan³, N. Almana², S. Alajmi², M. Alduhaileb², A. Abbas³; ¹General Surgery, KFSHD, Dammam, SAUDI ARABIA, ²Breast Surgery, KFSHD, Dammam, SAUDI ARABIA, ³Breast and Endocrine surgery, KFSHD, Dammam, SAUDI ARABIA.

Background: Breast conserving surgery for locally advanced breast cancer remains a controversial approach,Historically mastectomy has been the preferred surgical intervention for patients with T3/T4 breast cancer.However,the utilization of neoadjuvant systemic therapy (NAST), development of oncoplastic breast conserving techniques rendered BCS an increasingly appealing option for patients and surgeons.Methodology: Study aims to evaluate the surgical and oncological safety of BCS for non-inflammatory, non-multicentric T3/T4 non-metastatic breast cancer through a retrospective analysis of prospectively maintained data. 75 female patients diagnosed between 2017 and 2024. Analysis encompassed clinico-pathological characteristics, treatment modalities and surgical outcomes, including surgical margins, rates of margin re-excision and conversion to mastectomy and pathologic complete response (PCR) or down-staging to a lower tumor stage after NAST. Oncological outcomes included disease recurrence and overall survival.Result: Out of 75 patients, 43 (57%) had T3 lesion,32 (43%) had a T4a-c lesion. Mean age of patients was 52 years. Most of patients had an invasive ductal histology (95%) of high grade (71%), node positive (60%). Luminal type comprised 41%,37% triple negative and 21% were HER2neu positive. BCS associated with positive surgical margins in 2 patients (2.6%) one underwent margin re-excision (1.3%), other patient (1.3%) converted to mastectomy for margin clearance. Most of the patients received NAST; 63 (84%) chemotherapy, 6 (8%) hormonal therapy. Majority (93%) received adjuvant radiotherapy. PCR observed in 31(45%) patients,35 (50%) achieved down-staging to smaller tumor size, including patients with triple negative or HER2 positive. 3 patients (5%) with luminal type failed to achieve pathological response to NAST and had identical clinical and pathological tumor stages. On multivariate analysis, patients with TN (70%) and HER2 positive (50%) were likely to achieve PCR after NAST, compared to patients with luminal type (8%) (P<0.001). with average follow up duration of 34 months, our cohort demonstrated an overall survival rate of 95%. While the majority of patients remained disease-free, Tumor recurrence was observed in 10 (13%) patients. No isolated local recurrences. Most recurrences were systemic (11%), compared to one systemic and local, and another Locoregional recurrence (1% each). Systemic recurrences were predominantly associated with HER2 positive (50%) grade 3 (60%) and characterized by the lack of PCR (78%) after NAST. However, this did not correlate to statistical significance. Discussion: Data demonstrates that BCS for T3/T4 non inflammatory breast cancer after NAST is associated with low rates of positive surgical margins and conversion to mastectomy, while maintaining acceptable outcomes after oncoplastic surgery, including level 1 and 2, therapeutic reduction mammoplasty, and chest wall perforator flap reconstruction. Isolated local recurrence was rare, and most recurrences were systemic, suggesting that treatment failure was primarily systemic rather than regional. Interestingly, the two patients who experienced local recurrence had negative surgical margins following BCS; however, they did not receive adjuvant radiation, and both had a triple positive, the association between local recurrence and HER2-positive subtype, high tumor grade, and lack of PCR highlights the impact of tumor biology on prognosis conclusion, BCS for non-inflammatory T3/T4 breast cancer appears to be both surgically and oncologically safe after NAST. Therefore, it should be considered and thoroughly discussed with the patient as a viable treatment alternative to mastectomy.

Z. Shi, R. Jia, Y. Wang, P. Qiu; Breast Cancer Center, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, CHINA.

Background: Internal mammary sentinel lymph node biopsy (IMSLNB) is a minimally invasive diagnostic technique for assessing regional lymph nodes, which provides precise lymph node staging and informs adjuvant treatment decisions. However, its prognostic impact remains uncertain, resulting in ongoing debate regarding its clinical application. This study aims to investigate the long-term prognostic outcomes of IMSLNB in patients with early-stage breast cancer.Methods: This study performed a retrospective cohort analysis involving 10,923 breast cancer patients who visited our hospital between January 1, 2013, and December 31, 2022. Following propensity score matching, the patients were categorized into two groups: the IMSLNB group and the no-IMSLNB group. The prognostic outcomes of these two groups were compared. The primary endpoint of this study was disease-free survival (DFS), while secondary endpoints included overall survival (OS), regional recurrence-free survival (RRFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS).Results: A total of 1608 patients were included in the final analysis, with 536 in the IMSLNB group and 1072 in the no-IMSLNB group. In the IMSLNB group, 93 patients were identified with IMSLN metastasis, yielding a metastasis rate of 17.4%. Among these, 82 had concurrent axillary lymph node (ALN) metastasis, while 11 exhibited isolated IMSLN metastasis. The median follow-up duration was 60.9 months. The findings demonstrated that the 5-year DFS (95.9% vs. 93.9%; HR, 0.562; 95% CI, 0.364-0.869; P=0.010) was significantly higher in the IMSLNB group compared to the no-IMSLNB group. However, there was no statistically significant difference in the 5-year overall survival (OS) rates between the two groups (98.9% vs. 98.5%; HR, 0.487; 95% CI, 0.208-1.141; P=0.098).The 5-year RRFS (99.4% vs 98.4%, HR, 0.360; 95% CI, 0.145-0.890; P=0.027) and LRFS (99.6% vs 98.5%, HR, 0.380; 95% CI, 0.118-0.800; P=0.016) in the IMSLNB group were significantly superior to those in the no-IMSLNB group; however, there was no statistically significant difference observed in the 5-year DMFS (96.8% vs 97.0%, HR, 0.843; 95% CI, 0.472-1.508; P=0.565) between the two groups.Exploratory subgroup analysis of disease-free survival (DFS) revealed that patients within specific subgroups, including diagnostic age (>50 years), mastectomy, absence of lymphovascular invasion (LVI), pathological type as invasive ductal carcinoma, and negative axillary lymph node (ALN) status, demonstrated significant benefit from IMSLNB (P<0.05).Conclusion: IMSLNB enables more precise regional lymph node staging for early-stage breast cancer, facilitates the optimization of adjuvant radiotherapy strategies, thereby enhancing RRFS, LRFS, and DFS outcomes. It can be recommended as a minimally invasive technique for regional lymph node staging.

B. Keizers¹, J. J. Nijveldt², T. S. Nijboer³, H. H. Boersma⁴, F. J. Voskuil³, A. H. de Haas⁵, S. Kruijff², P. J. van der Zaag⁶, W. Kelder⁷; ¹Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, Groningen, NETHERLANDS, ²Surgery, University Medical Center Groningen, Groningen, NETHERLANDS, ³Oral and Maxillofacial Surgery, University Medical Center Groningen, Groningen, NETHERLANDS, ⁴Clinical Pharmacy and Pharmacology, University Medical Center Groningen, Groningen, NETHERLANDS, ⁵Pathology and Medical Biology, Academic Breast Center Groningen, location Martini Hospital, Groningen, NETHERLANDS, ⁶Molecular Biophysics, University of Groningen, Zernike Institute, Groningen, NETHERLANDS, ⁷Surgery, Academic Breast Center Groningen, location Martini Hospital, Groningen, NETHERLANDS.

Introduction Tumor-positive margins are reported in 10-11% of patients undergoing breast-conserving surgery (BCS) for breast cancer and require additional therapy (boost radiotherapy or re-excision) to reduce local recurrence risk. Fluorescence imaging (FI) shows promise in reducing tumor-positive margins by intraoperative tumor tissue visualization using tumor-specific tracers. This clinical study aims to identify tumor-positive margins intraoperatively using FI with bevacizumab-IRDye800CW, and assess the feasibility of implementing FI in high-volume breast cancer centers. Methods Patients with early-stage breast cancer scheduled for BCS were included. Bevacizumab-IRDye800CW was administered intravenously 2-4 days prior to surgery. After the lumpectomy, fluorescence images of both the surgical cavity and resection specimen were obtained. While surgeons proceeded with the sentinel node procedure, the fluorescence images were analyzed and a tumor-to-background (TBR) ratio of higher fluorescence intensity spots were calculated. A TBR >1.5 was considered a risk of a tumor-positive margin and re-excision of the corresponding area was performed in consultation with the surgeon. All fluorescence images were correlated to histopathology results. Results In total, 53 patients completed all study procedures. Five patients (9.4%) initially had a tumor-positive margin. FI identified all those patients. Re-excision was performed in the same session, resulting in tumor-negative margins in all these cases. In 35 other patients re-excisions were performed because of a high TBR. In hindsight, they had negative margins, but the re-excision was generally performed at the side with the closest margin based on histopathology assessment. Incorporation of FI prolonged the average BCS time by a maximum of five minutes. Conclusion Targeted-fluorescence guided re-excisions prevented tumor-positive margins in 9.4% of patients undergoing BCS for breast cancer. In our study, no tumor-positive margins were missed and tumors were confirmed to be completely resected. With only a five-minute increase in surgery time, FI seems feasible to implement in a high-volume breast cancer center. Further optimization of tracer specificity and signal depth quantification is needed to improve accuracy and clinical applicability.

R. Yamakado¹, A. Noro¹, R. Ito¹, N. Imai¹, M. Shibusawa¹, M. Kimoto¹, M. Yoshikawa¹, K. Nakamura¹, E. Hatakawa¹, S. Watanabe¹, M. Yoshida¹, T. Mitsui¹, E. Matsumoto², C. Mizumoto², N. Hanamura³, T. Nishimine³, Y. Kashikura³, M. Yamashita⁴, R. KoJima⁴, Y. Nomoto¹, T. Ogawa², K. Kawaguchi¹; ¹breast center, Mie medical University, Tsu, JAPAN, ²breast center, Japanese Red Cross Ise Hospital, Ise, JAPAN, ³breast center, Saiseikai Matsusaka General Hospital, Matsusaka, JAPAN, ⁴breast center, Mie prefectural general　Medical center, Yokkaichi, JAPAN.

Background:Whole-breast irradiation after breast-conserving surgery (BCS) is a standard treatment for breast cancer. Boost radiation is recommended in cases with positive surgical margins, and recently, its application has expanded to younger patients with negative margins to reduce local recurrence. At our center and affiliated institutions in Mie Prefecture, oncoplastic breast-conserving surgery (OPBCS) has been actively implemented over the long term, aiming to achieve both oncological safety and favorable cosmetic outcomes. OPBCS includes volume displacement techniques using intra-breast tissue and volume replacement techniques using autologous tissue, which may obscure the tumor bed and margins due to extensive tissue rearrangement, raising concerns regarding radiotherapy targeting accuracy.Methods:This multicenter retrospective observational study included 4215 patients who underwent primary breast cancer surgery from January 2017 to December 2023. The study aimed to evaluate the safety and treatment outcomes of postoperative radiotherapy in patients who received OPBCS. The primary endpoint was ipsilateral breast tumor recurrence (IBTR), while secondary endpoints were overall survival (OS), event-free survival (EFS), the interval from surgery to initiation of radiotherapy, and the incidence of radiotherapy-related complications.Results:The median observation period was 55 months in the OPBCS group and 54 months in the non-OPBCS group. Patient characteristics revealed a higher rate of re-excision in the OPBCS group. IBTR showed no significant difference between the groups (p = 1.0; OR, 0.97; 95% CI, 0.16-4.59). OS was significantly better in the OPBCS group (p = 0.0284; OR, 0.22; 95% CI, 0.025-0.95), while EFS was comparable between the groups. The median interval from surgery to radiotherapy initiation was longer in the OPBCS group (48 days) than in the non-OPBCS group (40 days) (p < 0.001); however, no significant difference was observed for delays beyond 16 weeks. Multivariate analysis identified OPBCS as an independent factor associated with delayed initiation of radiotherapy. The OPBCS group also exhibited a significantly higher incidence of postoperative complications (p < 0.001; OR, 2.24; 95% CI, 1.52-3.31), which was considered a major contributor to the delay. Notably, the incidence of radiotherapy-related complications, excluding grade 1 dermatitis, did not differ between groups (p = 1.0). Discussion:Postoperative complications likely contributed to delayed radiotherapy in the OPBCS group. Surgeons may also intentionally delay radiotherapy initiation to preserve vascular supply in rearranged tissue. However, with a median delay of only 48 days (~7 weeks), and no difference in IBTR rates, OPBCS does not appear to negatively impact oncologic outcomes and should not be considered a barrier to its broader adoption.

R. N. Rohrich¹, H. Soltani¹, I. A. Snee¹, K. L. Fan¹, L. De La Cruz²; ¹Plastic and Reconstructive Surgery, Medstar Georgetown University Hospital, Washington, DC, ²Division of Breast Surgery, Medstar Georgetown University Hospital, Washington, DC.

Background: Since our 2015 manuscript, nipple-sparing mastectomy (NSM) continues to be an increasingly adopted technique in breast cancer management. However, concerns regarding long-term oncologic safety still persist. This systematic review and meta-analysis provides a ten year update on oncologic safety associated with NSM, specifically overall survival (OS), disease-free survival (DFS), local recurrence (LR), and nipple-areolar complex recurrence (NACR). Methods: A systematic review of the literature was performed according to PRISMA guidelines to identify studies reporting outcomes after NSM. Studies with internal comparison arms evaluating therapeutic NSM versus skin-sparing mastectomy (SSM) and/or modified radical mastectomy (MRM) were included in a meta-analysis of OS, DFS, and LR. Studies lacking comparison arms were only included in the systematic review, wherein pooled analyses for NSM patients were conducted for OS, DFS, LR, and NACR using a random-effects model. Weighted averages and 95% confidence intervals (CI) were calculated, and studies were stratified by duration of follow-up: 10 years. Results: A total of 60 studies representing a total of 7,752 patients undergoing NSM were included. The meta-analysis included 11 studies with comparison arms (Figure 1). Nine studies reported OS with a significant pooled risk difference of 2.1% favoring NSM over MRM/SSM (95% CI: 0.0-4.3%, p=0.047). Seven studies reported DFS, with a nonsignificant pooled risk difference of 4.8% favoring NSM (95% CI: -0.8-10.3%, p=0.093). Eleven studies reported LR, with a nonsignificant pooled risk difference of -0.7% (95% CI: -2.1-0.8%, p=0.35). The systematic review included all 60 studies. Weighted average follow-up ranged from 25.6 to 133.4 months across groups. Among patients with 10 years follow-up (n=391), OS was 82.0% (80.9-93.2), DFS 60.7% (58.8-62.7), LR 15.1% (13.9-16.2), and NACR 1.1% (1.0-1.1). Conclusions: This study continues to support that NSM is associated with excellent overall and disease-free survival with low local recurrence rates comparable to that of SSM/MRM as well as low NAC recurrence rates among appropriately selected patients. This updated data provide additional support for the long-term safety of NSM.

L. De La Cruz¹, R. N. Rohrich², A. Junn², M. E. Currin², D. H. Song², K. L. Fan²; ¹Division of Breast Surgery, Medstar Georgetown University Hospital, Washington, DC, ²Plastic and Reconstructive Surgery, Medstar Georgetown University Hospital, Washington, DC.

Background: The anatomic boundaries of conventional nipple-sparing mastectomy (NSM) is poorly defined. As such, deeper support structures, such as the circummammary ligament, the anterior lamellar fascia, and adjacent perforators, lymphatics and nerves are disrupted, compromising perfusion, wound healing, and reconstructive outcomes. The structural mastectomy preserves these structures to enhance perfusion, reduce complications, and facilitate direct-to-implant (DTI) reconstruction without acellular dermal matrices in the prepectoral plane. This study evaluates reconstructive outcomes associated with structural versus conventional NSM with immediate DTI reconstruction. Methods: A retrospective review was conducted of all patients who underwent NSM with DTI reconstruction at a single institution between November 2020 and July 2024. Patients were stratified by mastectomy technique into those who received a structural NSM (s-NSM) and those who underwent conventional non-structural NSM. s-NSM was characterized by the preservation of the circummammary ligament, superficial fascial system, and associated neurovascular bundles through dissection along well-visualized planes through a 6 cm incision. Primary outcome was short-term (≤30 days) and long-term (>30 days) reconstructive complications. Results: A total of 122 patients (225 breasts) underwent conventional NSM (135 breasts, 60.0%) or s-NSM (90 breasts, 40.0%) with immediate DTI reconstruction. Baseline demographics, comorbidity profiles, and oncologic indications were similar between groups. Compared with conventional NSM, s-NSM was associated with shorter operative time (p=0.002), lower ADM use (55.6% vs. 94.1%, p<0.001), and greater rates of NAC reinnervation (70.0% vs. 26.7%, p<0.001). Oncologic outcomes were equivalent between groups. Short-term complications occurred less frequently following s-NSM (5.6% vs. 20.0%, p=0.003), including a significantly lower rate of partial nipple-areola complex necrosis (1.1% vs. 8.2%, p=0.030). On multivariate analysis, s-NSM remained independently protective against short-term reconstructive complications (OR 0.09, 95% CI 0.02-0.50, p=0.006), with good model discrimination confirmed by an area under the curve value (AUC) of 0.80. Long-term complication rates were also significantly less common following s-NSM (2.2% vs. 11.1%, p=0.018), though this did not remain statistically significant on multivariate analysis. The s-NSM was also associated with a significantly lower incidence of capsular contracture (2.2% vs. 11.1%, p=0.018). While fewer patients in the s-NSM cohort underwent elective aesthetic revision (11.1% vs. 20.0%, p=0.078), this did not reach statistical significance. Rates of positive margins (NSM: 3.7% vs. s-NSM: 3.6%, p=1.000), local recurrence (3.0% vs. 0.0%, p=0.529), distant metastasis (6.1% vs. 0.0%, p=0.117), and cancer-related death (5.3% vs. 0.0%, p=0.107) did not differ significantly. No differences in the instance of residual disease, tumor size, nodal metastasis, extranodal extension, or pathologic staging was observed between groups upon evaluation of final tumor pathology. Conclusion: For the first time, we demonstrate that structural preservation in breast surgery allows for efficacious single-stage reconstruction, limits ADM use, and improves reconstructive complication profiles early 1-year follow-up. While oncologic outcomes were not the primary focus of this study, overall survival and local recurrence rates were similar to those reported in prior series. The structural NSM may represent a paradigm shift in oncoplastic breast surgery in appropriately selected patients contributing to more favorable reconstructive outcomes.

T. Cheung¹, S. Patil², M. Nelis³, S. A. Valente¹, J. E. Lang⁴; ¹Breast Surgery, Cleveland Clinic, Cleveland, OH, ²Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, ³Obstetrics and Gynecology, Cleveland Clinic, Cleveland, OH, ⁴Breast Surgery and Cancer Biology, Cleveland Clinic, Cleveland, OH.

Background: The Choosing Wisely (CW) campaign issued by the Society of Surgical Oncology recommends omitting sentinel lymph node biopsy (SLNB) in women over age 70 with early-stage hormone receptor (HR) positive, HER2 negative breast cancer. The publication of the SOUND and INSEMA trials recently expanded indications for considering the omission of SLNB in younger women. We hypothesized that the rate of omission of SLNB has increased over time. Our primary objective was to define predictors of omitting SLNB and secondarily, to determine the incidence of patients beyond the CW population having omission of SLNB. Methods: We utilized the National Cancer Database (NCDB) to query between 2018-2021 for patients with cT1 or cT2 invasive breast cancer treated with breast surgery without use of neoadjuvant therapy. We recorded surgical procedure types, biomarkers, grade, the number of clinical and pathologic positive nodes, Charlson-Deyo Score, race/ethnicity, age, urban/rural setting, histology, and academic/community setting. Univariate analysis with the Pearson’s Chi-squared test and multivariable analysis with logistic regression were performed to identify factors associated with omission of SLNB. Univariate analysis was also performed to identify variables associated with rates of breast conserving surgery (BCS) versus mastectomy. Results: Overall, 433,737 patients met study inclusion criteria with 313,201 (72%) treated with BCS while 120,536 (28%) were treated with mastectomy. In our cohort, 133,169 (31%) were over age 70 and 368,228 (86%) were HR+/HER2-. Only 4219 patients (1%) had omission of SLNB, of which 3599 (88%) were HR+/HER2-, 247 (6.0%) were HER2+, and 238 (5.8%) were triple negative. Omission of SLNB did not increase over time with rates ranging from 0.06%-1.6% of the overall study population by year. On multivariable analysis, predictors of omitting SLNB were age >70 (OR 1.51, CI 0.86-0.97), non-zero Charlson-Deyo Score (p<0.001), HR+/HER2- (OR 1.09, CI 1.06-1.13), year of diagnosis 2021 (OR 1.56, HR 1.52-1.6), non-lobular histology (p<0.001), academic setting (p<0.001), and metropolitan setting (p<0.001). White race was associated with omitting SLNB but was only marginally significant on univariate analysis (p=0.047). Type of surgery as BCS was associated with omission of SLNB (p<0.001) on univariate analysis only. Most patients who had omission of SLNB had cT1 disease (n=3409 or 83% of patients having no nodal surgery while fewer patients with cT2 status had no nodal procedure (n=722, 17%), p<0.001). Of patients having no SLNB, 98% were cN0, 2% were cN1, 0.2% were cN2 and <0.1% were cN3. Conclusions: Rates of the omission of SLNB did not increase over time from 2018-2021 despite the publication of the Choosing Wisely recommendations in 2016 to consider omitting SLNB in patients over age 70 with HR positive, HER2 negative early-stage breast cancer. Only 1% of breast cancer patients had omission of SLNB despite 31% of the cohort being over age 70. Age >70, non-zero Charlson-Deyo Score, HR+/HER2- status, year of diagnosis 2021, non-lobular histology, academic and metropolitan setting were associated with omission of SLNB. These data provide estimates that may be used in the future to compare the impact of the SOUND and INSEMA trial on rates of omission of SLNB based on prospective randomized controlled trials that expand criteria for omission of SLNB beyond the Choosing Wisely guidelines.

D. B. Lipps¹, B. D. Baglien², M. N. Saunders³, J. Vidergar⁴, G. L. Maica³, P. L. Myers², M. Banerjee⁴, A. O. Momoh²; ¹School of Kineisology, University of Michigan, Ann Arbor, MI, ²Plastic Surgery, University of Michigan, Ann Arbor, MI, ³Medical School, University of Michigan, Ann Arbor, MI, ⁴School of Public Health, University of Michigan, Ann Arbor, MI.

Background: Post-mastectomy breast reconstruction is a crucial component in improving psychosocial outcomes and quality of life for breast cancer survivors. Prepectoral implant-based breast reconstruction has gained traction over the past decade due to its potential to enhance aesthetic results and reduce muscle disinsertion-related complications. Wider adoption is limited by concerns over potentially higher healthcare costs compared to the previously traditionally favored subpectoral approach. Prior research on the cost implications of these methods has produced mixed results, often lacking comprehensive analyses of cumulative perioperative medical expenses. Methods: This retrospective cohort study analyzed data from women who underwent unilateral or bilateral mastectomy followed by immediate implant-based reconstruction at a single academic center between July 2017-June 2022. The study period marked a transition in institutional practice from predominantly subpectoral to prepectoral procedures. We examined billing charges from the index surgery and the downstream costs of patient care up to six months post-operation. Regression analyses assessed total index surgery costs, downstream costs, and cumulative costs, adjusting for variables such as age, BMI, and racial demographics. Results: The study analyzed data from 185 patients—86 underwent prepectoral and 99 underwent subpectoral reconstruction. Demographic analysis revealed no significant differences in baseline characteristics such as age, BMI, or intraoperative time between groups. Subpectoral reconstructions had significantly lower index surgery costs, with a 30.5% decrease in costs compared to prepectoral reconstruction (p < 0.001). While downstream costs up to six months post-surgery did not significantly differ, a trend towards reduced expenses was noted following subpectoral procedures (p = 0.094). Cumulative costs, driven by initial surgery expenses, were 29.2% lower in subpectoral cases (Table, p < 0.001). The increased use of acellular dermal matrix in prepectoral procedures was identified as a major factor contributing to higher costs. Conclusions: Our findings demonstrate that prepectoral implant-based reconstruction is associated with significantly higher surgical and cumulative costs compared to subpectoral reconstruction. No substantial differences were observed in postoperative care costs, suggesting that the increased expense of prepectoral approaches is primarily driven by the higher cost of surgical adjuncts during the index surgery. These results provide critical cost-related insights as prepectoral techniques, including the need to use lower-cost surgical adjuncts. Addressing these cost variables could facilitate broader implementation of prepectoral procedures, leveraging their potential patient-centered benefits.

C. Lee¹, J. Ryu¹, S. Ahn², J. Lee³, H. Shin⁴, J. Lee⁵, Y. Kwak⁶, H. Lee⁷, S. Nam¹, S. Kim¹, J. Lee¹, J. Yu¹, B. Chae¹, S. Lee¹, W. Park¹, K. Kim¹, S. Lee¹; ¹Department of Surgery, Samsung Medical Center, Seoul, KOREA, REPUBLIC OF, ²Department of Surgery, Gangnam Severance Hospital, Seoul, KOREA, REPUBLIC OF, ³Department of Surgery, Kyungpook National University Chilgok Hospital, Daegu, KOREA, REPUBLIC OF, ⁴Department of Surgery, Myongji Hospital, Seoul, KOREA, REPUBLIC OF, ⁵Department of Surgery, Soonchunhyang University Hospital, Seoul, KOREA, REPUBLIC OF, ⁶Department of Surgery, Chung-Ang University Hospital, Seoul, KOREA, REPUBLIC OF, ⁷Department of Surgery, Seoul National University Hospital, Seoul, KOREA, REPUBLIC OF.

Background: In patients with clinically node-positive breast cancer undergoing chemotherapy, sentinel lymph node biopsy has been associated with a false-negative rate up to 14% according to previous studies. However, when target axillary dissection techniques, such as the placement of clips or markers in biopsy-proven metastatic lymph nodes, are employed, false-negative rates have been reported to decrease dramatically to approximately 1.4%, as shown in a pivotal study published in 2016. Despite this evidence, there has been no large-scale evaluation of axillary lymph node targeting methods in Korean clinical setting. This study aims to establish foundational data for targeted axillary strategies in Korea by comparing different localization methods used in patients with initially node-positive breast cancer. Methods: This study was conducted as a retrospective multicenter study involving patients with biopsy-proven node-positive breast cancer, who underwent surgery between January 2015 and June 2024. Patients were enrolled from seven institutions based on the following inclusion criteria; primary unilateral breast cancer, clinical tumor stage cT1-T4, biopsy-proven metastatic axillary lymph node with marker placement, and age over 18 years. Detailed analyses were conducted regarding the extent of axillary surgery, the type of marker used (clip or tattoo), and the use of localization techniques such as wire localization. Results: A total of 331 patients were included and the mean age was 49.3 years with 31 months of median follow-up. According to marking methods, targeted lymph nodes were successfully identified in 127 out of 145 patients (87.6%) who received clip markers, and in 178 out of 184 patients (96.7%) who underwent tattoo marking. There were no significant differences in concordance between sentinel lymph node and targeted lymph node across the clip and tattoo group (66.2% vs. 79.3%, p=0.298). Discordance between the sentinel lymph node and targeted lymph node was observed in 12.1% of total patients, 13.8% of patients in the clip marker group and 10.9% in the tattoo marker group. Among the clip group, patients who underwent wire localization showed a non-significant trend toward lower concordance between sentinel lymph node and targeted lymph node compared to those without wire localization (66.7% vs. 83.3%, p=0.069). Demographics and treatment characteristics, including tumor stage, surgery type, and systemic therapy, did not differ significantly between different markers. Conclusions: This is the first multicenter analysis in Korea focusing on targeting methods for metastatic axillary lymph nodes. No significant difference was observed in sentinel lymph node-targeted lymph node concordance and targeted lymph node detection between the clip and tattoo marker groups, suggesting that both methods have comparable feasibility in planning targeted axillary surgery. Interestingly, tattoo-based marking was used at a frequency comparable to clip marking, which contrasts with global trends. This may be attributed to the limited use of clip markers in Korea due to reimbursement restrictions. Also, these findings are clinically meaningful when considered in the context of the well-established false-negative rate of approximately 14% reported in node-positive breast cancer patients undergoing sentinel lymph node biopsy, suggesting that appropriate lymph node targeting strategies may help reduce discordance and improve surgical accuracy.

G. Agarwal¹, S. Dariya¹, S. Mayilvaganan¹, G. Chand¹, A. Mishra¹, N. Mohindra², V. Agrawal³, P. Mishra⁴; ¹Department of Endocrine & Breast Surgery, SGPGIMS, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Lucknow, INDIA, ²Department of Radiology, SGPGIMS, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Lucknow, INDIA, ³Department of Pathology, SGPGIMS, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Lucknow, INDIA, ⁴Department of Biostatistics, SGPGIMS, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, Lucknow, INDIA.

BACKGROUND: Predicting response to NAST may help tailor treatment, maximize pCR rates and de-escalate surgery (BCS, SLNB). We tested if multiparametric imaging- using mammography breast tomosynthesis (DBT), ultrasound shear wave elastography (SWE) & color Doppler after 2 NAST cycles (post2NAST) of their changes from baseline correlate with NAST response and predict pCR. METHODS: In this prospective study, 100 non-metastatic breast ca pts (39 TNBC, 31 HER2 enriched, 28 Luminal B like) receiving NAST underwent imaging at baseline, post2NAST, after completing NAST. Changes in tumor dimensions, volume, density, stiffness, vascularity were correlated with pCR & RCB after surgery. RESULTS: 40% achieved pCR. Post2NAST DBT density changes predicted pCR (p<0.0001); 92% patients with pCR had decreased density. Density post2NAST was strongly associated with response- 87% low-density tumors had low RCB (0-1), c.w. 88% persistent high-density tumors had poor response (RCB 2-3)- 87% sensitivity, 80% specificity. Post2NAST, ≥17.6% reduction in max diam predicted pCR with 82.5% sensitivity, 70% specificity (AUC = 0.817), while ≥39.4% vol. reduction predicted pCR with 87.5% sensitivity, 70% specificity (AUC = 0.824). Mean & max SWE values from tumor core, peritumoral zone & large ROI were studied. Only mean, max peritumoral SWE baseline→ post2NAST reduction was significantly assoc. with pCR (p=0.038, 0.020 respectively). Absolute SWE values post2NAST or post NAST across all regions didn’t distinguish responders. Baseline→ post2NAST reduction in Adler vascular score (semi-quantitative Doppler grading that classify vascularity/angiogenesis) was significantly assoc. with pCR, p=0.002. Patients achieving ‘No flow’ had highest pCR (71.4%). A ≥2-point drop demonstrated high 87% specificity for pCR. Mean 13-point vascular imaging score declined significantly (baseline 9.6→ 6.9 post2NAST). On ROC analysis, score ≤6 post2NAST predicted pCR with 77% sensitivity, 60% specificity (AUC = 0.695, p=0.001). Subtype analysis: HER2+ tumors had greatest DBT density reduction after NAST (87.1%, p=0.038), closely mirroring their highest pCR rates. TNBC &HER2+ subtypes had greater stiffness reductions on SWE post2NAST, esp. in peritumoral mean/max & large ROI values (AUC 0.70). While Adler score regression (to “no flow”) was commonest in TNBC, subtype difference didn’t reach significance. Luminal B tumors consistently showed least favorable imaging response. CONCLUSIONS: Early imaging response post2NAST, especially DBT density/volume reduction & peritumoral SWE stiffness reduction strongly predict pCR, outperforming absolute values. Multiparametric imaging combining DBT, SWE & Doppler vascular scores (Adler & 13-point) offers a non-invasive, early surrogate for treatment response, enabling timely therapy tailoring, and predicting pCR.

E. C. Namoglu¹, A. Meisner², M. R. Flanagan³, E. F. Gillespie¹; ¹Department of Radiation Oncology, University of Washington, Seattle, WA, ²Public Health Sciences Division, Fred Hutch Cancer Center, Seattle, WA, ³Department of Surgery, University of Washington, Seattle, WA.

Background: In April 2025 the American Society for Clinical Oncology (ASCO) published practice-changing guidelines recommending the omission of sentinel lymph node biopsy (SLNB) in patients with early-stage breast cancer over the age of 50. We aimed to evaluate factors associated with a positive SLNB and the impact on adjuvant therapy among patients meeting updated ASCO Guideline recommendations for SLNB omission. Methods: A single-institution retrospective cohort study of patients 50-70 years old diagnosed with early-stage invasive breast cancer (cT1N0, grade 1-2, ER+, HER2-) between 2022-2024 who underwent SLNB. All patients were cN0 and pre-operative axillary ultrasound (axUS) was not required. The primary outcome was SLNB positivity (SLNB+), defined as at least pN1mi, and secondary outcome was adjuvant treatment. Categorical covariates were compared in univariate analysis using Fischer’s exact test. Multivariable logistic regression was used to evaluate factors associated with SLNB+, adjusting for relevant clinical characteristics. Results: Among 282 patients meeting ASCO guideline criteria, 275 (97.5%) had SLNB results available for analysis. Among the cohort with SLNB, median age was 63 years (IQR 58-66) and the majority (81.0%) were ductal histology (Table 1). Adjuvant therapy included hormonal therapy (87.0%), whole breast radiation (73.0%), partial breast radiation (19.0%) and chemotherapy (5.8%). SLNB was positive in 17 (6.2%) patients (9 pN1mi, 8 pN1a, 0 pN2). Among those with pN1a, two patients had 2 positive nodes (one was pT2 and one had Oncotype Recurrence Score [RS] of 29) and no patients had 3 nodes. Factors associated with SLNB+ included tumor grade, pathologic tumor stage and Oncotype RS. In multivariable analysis, younger age and Oncotype RS were associated with SLNB+ but not tumor grade or tumor stage (Table 1). Among the 17 patients with SLNB+, 5 (29.4%) received chemotherapy of which 4 had a high Oncotype RS and 1 was pT2 on final pathology. Per 2024 Updated ASTRO Guideline, APBI would have been suitable for 8, and cautionary or not recommended for 6 patients with SLNB+ based on risk factors alone (3 pT2, 2 lobular histology, 1 with lymphovascular invasion [LVI]), and potentially 3 other patients with Oncotype RS >25. Among 8 patients with pN1a, 2 had a high-risk feature (both Ki67>20%) indicating eligibility for adjuvant CDK4/6i per 2024 ASCO Guideline. Conclusion: In this cohort of 50- to 70-year-old patients with cT1N0 tumors meeting ASCO Guidelines for SLNB omission in the real-world setting of inconsistent pre-operative axUS, 6.2% were SLNB+. No decisions about chemotherapy would have been affected by the omission of SLNB. The positive SLNB could have impacted a total of 10 (3.6%) patients who may have received APBI instead of WBRT or not been eligible for CDK4/6i.

M. Rana¹, A. C. Weiss², A. D. Laws³, C. Mita⁴, T. King⁵; ¹Surgery, University of Saskatchewan, Regina, SK, CANADA, ²Division of Surgical Oncology, University of Rochester School of Medicine and Dentistry, Rochester, NY, ³Department of Oncology, Cumming School of Medicine, University of Calgary, Calgary, AB, CANADA, ⁴Countway Library, Harvard University, Harvard Medical School, Boston, MA, ⁵Department of Surgery, Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston, MA.

Background: The optimal management of the axilla following neoadjuvant chemotherapy (NAC) for initially node-positive breast cancer (cN+) remains contentious, although there has been a trend towards de-escalating morbid axillary surgery under certain conditions. Clinically node-positive breast cancer that converts to node-negative (ypN0) following NAC is increasingly being managed by sentinel lymph node biopsy (SLNB) alone rather than by axillary lymph node dissection (ALND). Recent consensus by experts in St. Galen [Ditsch et al, 2025] suggest SLNB alone may also be acceptable for low volume residual axillary nodal disease (ypN1) following NAC, although data to support the oncologic safety of this approach are limited. The aim of this meta-analysis was to evaluate the long-term oncologic outcomes of SLNB alone for residual axillary nodal disease following NAC. Methods: A systematic review and meta-analysis was conducted according to PRISMA guidelines. Medline (Ovid), Embase, and Cochrane Central Registry were systematically searched for studies comparing women undergoing SLNB or ALND following NAC for initially clinically node-positive breast cancer (cN+). Included studies reported one of the following outcomes: axillary recurrence (AR), locoregional recurrence (LRR), distant recurrence (DR), disease-free survival (DFS) or overall survival (OS). A random effects meta-analysis was used to calculate weighted pooled effect estimates (risk ratios, RR) for all outcomes, comparing SLNB alone with ALND for patients with residual nodal disease (cN+/ypN+). Variability across studies due to heterogeneity was estimated using I² statistics. Results: Fourteen observational studies were eligible for meta-analysis, providing data for 9,518 patients. The median age of the women included in the studies ranged from 47 to 53 years. Seven studies included only cN1 cases (pre-NAC), with 8 studies reporting outcomes for only ypN1 cases. The median number of sentinel lymph nodes retrieved in each study ranged from 2 to 6. The median follow-up time ranged from 28 to 108 months. The rates of axillary recurrence ranged from 0.2% to 7.8% across all included studies. Distant recurrence rates ranged from 15.7% to 38.6%. No significant differences were observed in AR between patients undergoing SLNB alone versus ALND following NAC: pooled RR 1.12 (95% CI: 0.72-1.74, I²=0.0%). Similarly, no significant differences were observed in LRR (RR 0.97, 95% CI: 0.68-1.37, I²=0.0%) nor overall mortality (RR 0.96, 95% CI: 0.65-1.42, I²=58.3%) between the two groups. However, the pooled risk of distant recurrence was lower for SLNB alone compared to the ALND group (RR 0.75, 95% CI: 0.60-0.95, I²=0.0%). Conclusions: This meta-analysis suggests that long-term outcomes of SLNB alone for breast cancer with residual axillary nodal disease following NAC are not inferior to those of ALND. AR rates were low across all included studies; the majority of recurrences were distant, questioning the need for aggressive axillary surgery for patients with low volume residual nodal disease. We await prospective data from several randomized clinical trials, including Alliance A011202 and MAC 19, to further guide axillary management in this group of patients. References:Ditsch et al (2025) St. Gallen/Vienna 2025 Summary of Key Messages on Therapy in Early Breast Cancer from the 2025 St. Gallen International Breast Cancer Conference. https://doi.org/10.1159/000546080

D. Hequet¹, M. Cittanova², R. Salmon³, M. Wilhelm¹, G. Aubry¹, C. Gout Duracher², J. Seror¹; ¹Surgery, Institut Bourdonnais, Paris, FRANCE, ²Anesthesia, Clinique Saint Jean de Dieu, Paris, FRANCE, ³Surgery, Clinique Saint Jean de Dieu, Paris, FRANCE.

Background : Local anesthesia with sedation (LAS) is widely used in other surgical disciplines but remains underutilized in breast-conserving surgery (BCS), where general anesthesia (GA) is still the standard [1, 2]. Recent reports have demonstrated the potential of LAS in selected breast surgery cases [3-5]. We aimed to evaluate the feasibility of systematically performing BCS under LAS in a high-volume breast cancer center.Methods : We conducted a retrospective study including all patients who underwent BCS ± axillary surgery from September 2021 to December 2023 in our institution. Patients operated under GA during the initial period (Sept 2021-March 2022) were compared to those under LAS (June 2022-Dec 2023), excluding the transition phase. LAS combined intravenous sedation (midazolam, dexmedetomidine, ketamine, remifentanil) with local infiltration (naropeine, lidocaine with epinephrine, saline). Feasibility endpoints included conversion to GA, intraoperative tolerance, and early surgical complications.Results : Of the 948 BCS procedures performed during the study period, 708 (75%) were carried out under LAS. Among the eligible patients during the LAS period, 12 refused local anesthesia and were operated under GA. Only 2 conversions to GA occurred during LAS procedures (0.3%), confirming excellent feasibility. We planned more preoperative wire in the LAS group (80% vs. 59%) because of the aqueous environment making small lesions more difficult to feel. Re-operation rates (for positive margins, hematoma, or infection) did not differ between LAS and GA groups (11% in LAS group vs. 13% in GA group, p=0.34). Axillary procedures were performed in both groups (52% in LAS group and 58% in GA group, n=0.06). Oncoplastic techniques were successfully performed under LAS without compromising safety or outcomes. Conclusions : Our results confirm that systematic BCS under LAS is feasible, safe, and applicable to a wide range of breast surgical procedures, including oncoplastic and axillary surgeries. To our knowledge, this represents the largest reported single-center series of breast-conserving surgery performed under LAS, supporting its broader implementation in routine clinical practice and perioperative optimization strategies.References

1. D’Alonzo M, Martincich L, Biglia N, et al. Feasibility of breast surgery under local anesthesia in elderly patients. J Surg Oncol. 2020;121(3):446-453.
2. Fischer JP, Nelson JA, Sieber B, et al. Propensity-matched analysis of local versus general anesthesia for outpatient breast surgery. Ann Surg Oncol. 2014;21(10):3274-3280.
3. Boughey JC, Goravanchi F, Pockaj BA, et al. Anesthesia considerations in breast surgery. Breast J. 2020;26(4):727-732.
4. Peled AW, Foster RD, Esserman LJ. Increasing role of local anesthesia with sedation in breast surgery. Ann Surg Oncol. 2015;22(10):3336-3342.
5. Fernandez-Rodriguez M, Castano-Oreja MT, et al. Local anesthesia and sedation in breast-conserving surgery: A valid alternative to general anesthesia. Clin Transl Oncol. 2022;24(3):473-480.

J. Lucocq, R. Swan, A. Klenjnotowska, J. Dixon; Edinburgh Breast Unit, Western General Hospital, Edinburgh, UNITED KINGDOM.

Background: The impact of immediate lipofilling in the setting of breast conserving surgery on oncological outcomes are unknown. There is concern from in-vitro studies that adipose-derived stem cells may promote cancer recurrence through their proliferative properties. The aim of the present study was to investigate the long-term safety of breast conservation surgery (BCS) combined with immediate lipofilling. Methods: The patient cohort included 117 consecutive patients with invasive breast cancer or ductal carcinoma in situ (DCIS) who had BCS plus immediate lipofilling from 2011 to 2019 and 248 controls. Control patients had BCS without lipofilling in the same week as patients having BCS with lipofilling. Propensity score matching (PSM) was performed to determine the impact of immediate lipofilling on outcome where treatment (lipofilling) and control (no lipofilling) groups were matched for pathological and treatment variables. Multivariate survival analysis was performed to investigate the impact of lipofilling in subgroups according to T-stage, N-stage and tumour grade. The median follow up was 127 months. Results: There were 3 (2.5%) in-breast recurrences in lipofilled patients and 9 (3.6%) in the control group.When comparing lipofilled and non-lipofilled groups, there was no significant difference in overall survival (10-year, 94.8% vs. 93.3%; p=0.392), local recurrence (3.6% vs. 3.8%; p=0.601), regional recurrence (1.0% vs. 1.3%; p=0.761) and distant metastasis (5.8% vs. 3.3%; p=0.361). After propensity matching, lipofilling was not associated with mortality (log-rank, p=0.14), local recurrence (p=0.64), regional recurrence (p=0.91), or distant recurrence p=0.73). Across all pathological subgroups investigated, immediate lipofilling had no impact on overall survival or local recurrence (p>0.05). Conclusion: There is no evidence that immediate lipofilling performed at the same times as breast conserving surgery has any impact on mortality or on local, regional, systemic recurrence. This study shows the oncological safety of BCS plus immediate lipofilling.

A. Conversano¹, F. Loi², J. Blanc³, E. El Rassy², A. Di Meglio², J. M Ribeiro², A. Viansone², A. Puchar¹, J. Zeitoun¹, A. Turpin¹, A. Martin⁴, M. Fournier⁵, M. Gutowski⁶, C. Cheymol⁷, B. Sauterey⁸, P. Cottu⁹, A. Bertaut³, B. Pistilli²; ¹Department of Breast and Plastic Surgery, GUSTAVE ROUSSY, Villejuif, FRANCE, ²Department of Medical Oncology, GUSTAVE ROUSSY, Villejuif, FRANCE, ³Methodology and Biostatistics Unit, Centre Georges François Leclerc, Dijon, FRANCE, ⁴Data and Partnerships Department, UNICANCER, Paris, FRANCE, ⁵Oncology Department, Institut Bergonié, Bordeaux, FRANCE, ⁶Department of Surgical Oncology, Institut Régional du Cancer, Montpellier, FRANCE, ⁷Oncology Department, Centre Oscar Lambret, Lille, FRANCE, ⁸Oncology Department, Institut de Cancérologie de L’Ouest, Angers, FRANCE, ⁹Oncology Department, Institut Curie, Paris, FRANCE.

Background Targeted Axillary Dissection (TAD), which combines sentinel lymph node biopsy with excision of a pre-marked target lymph node, has been shown in clinical trials to improve staging accuracy and reduce false-negative rates in patients with early breast cancer (EBC) and clinically positive lymph nodes (cN+) undergoing neoadjuvant systemic therapy (NAST). By identifying NAST responders with limited residual nodal burden, TAD would enable omission of ALND in selected cases, thus reducing surgical morbidity. However, its potential applicability and impact in unselected real-world populations remain unclear. Methods Using data from the CANTO cohort (NCT01993498), a large French prospective study including patients with stage I-III EBC, we consecutively identified patients with cT1-T4 cN+ EBC treated with NAST between May 2012 and August 2022 who underwent ALND according to national guidelines implemented during the same period. The primary outcome was the proportion of patients who would have avoided ALND if TAD had been available, defined as the percentage of patients with cN+ EBC treated with NAST who achieved axillary pCR, according to changes in surgical management of the axilla consistent with ongoing international trials (NCT05462457, NCT04373655, NCT06092892, NCT04744506) and future guideline proposals. Additional outcomes included 3-year and 5-year rate of axillary recurrence, any invasive recurrence and the impact of ALND on quality of life (QoL) using arm symptom score on QLQ BR23. Results In total, 370 patients with cN+ EBC treated with NAST in the CANTO cohort were included, of whom 56 (15.1%) stage T1, 220 (59.5%) T2, 94 (25.4%) T3. Most of them were N1 (335 pts, 90.5%), 32 (8.7%) N2 and 3 (0.8%) N3. Pathological axillary response was available for 241 patients and 82/241 (34.0%) achieved complete pathological axillary response. Rates of complete response by BC subtype were as follows: 23/65 (35.4%) with HR-/HER2-, 37/76 (48.7%) with HER2+ and 22/100 (22.0%) with HR+/HER2- EBC. Pathological breast response was available for 255 patients and 100/255 (39.2%) had complete breast pCR. A dissociated pCR (axilla-breast) was observed in 62 patients of whom, 37 with residual cancer in axilla and 25 in the breast. Adjuvant treatments were: 356 (96.2%) locoregional radiotherapy, 27 (7.3%) chemotherapy, 224 (60.7%) hormonotherapy, 1 (0.3%) immunotherapy, 28 (7.6%) HER2-directed therapy (TDM-1, pertuzumab, trastuzumab). At a median follow-up of 93 months, 3 year-DFS was 78.3% (95%CI,73.8%;82.2%), with axillary recurrence 7.3% (n= 19/101 (18.8%) with HR-/HER2-, n= 2/122 (1.6%) with HER2+ and n=6/146 (4.1%) with HR+/HER2-; p<0.001), local recurrence 2.4%, distant relapse 16.5%. 5 year-DFS was 72.2% (95%CI, 67.2%; 76.5%), with axillary recurrence 8.4% (n=19/101 (18.8%) with HR-/HER-, n=3/122 (2.5%) with HER2+ and n=9/146 (6.2%) with HR+/HER2-; p<0.001), local recurrence 3.2%, distant relapse 20.8%. Overall, 108/323 (33.4%) patients experienced lymphoedema/arm pain after ALND. Conclusions This analysis showed that TAD could have been considered instead of ALND in around one third of patients treated with NAST, particularly those with HR-/HER2- or HER2+ EBC, having a higher likelihood of complete pathological response in the axilla. These findings underline the potential of TAD to replace ALND, especially when guided by clinical response and tumor subtype. Bibliography 1. Vaz-Luis I. ESMO Open. 2019;4(5):e000562. 2. Kuemmel S. Ann Surg. 2022 Nov 1;276(5):e553-e562. 3. Cabioglu. Ann Surg Oncol. 2025 Feb;32(2):952-966. 4. Zatecky L. World Journal of Surg Oncol, (2023) 21:252. 5. Nijveldt JJ. Ann Surg Oncol. 2024 Jul;31(7):4477-4486. 6. Kuemmel S. JAMA Surg. 2023 Aug 1;158(8):807-815

E. Kuehnle¹, L. Steinkasserer¹, C. Mueller¹, H. Kuehnle², K. Luebbe³, K. Noeding⁴, S. Noeding⁵, M. Arfsten⁶, P. Hillemanns¹, T. Park-Simon¹; ¹Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, GERMANY, ²Department of Human Centered Design and Engineering, University of Washington, Seattle, WA, ³Breast Center, DIAKOVERE Henriettenstift, Hannover, GERMANY, ⁴Department of Gynecology and Obstetrics, HELIOS Klinikum Hildesheim, Hildesheim, GERMANY, ⁵Department of Gynecology and Obstetrics, Gynäkoonkologische Praxis am Pelikan Platz, Hannover, GERMANY, ⁶Breast Center Schaumburg, Kreiskrankenhaus Stadthagen, Stadthagen, GERMANY.

Purpose: Mastectomy for large in situ carcinoma is a commonly used therapy. Currently most national and international guidelines recommend sentinel lymph node biopsy because unexpected invasive breast cancer after mastectomy is an indication for sentinel lymph node staging. This cannot be performed after mastectomy and complete axillary dissection would be necessary in these cases. SLN as well as axillary dissection both can cause lifelong complications, especially arm movement impairment. Therefore, the necessity for this additional procedure needs to be addressed. We sought to gain insight into the frequency of unexpected upstaging to invasive breast cancer in case of mastectomy for in situ carcinoma and invasive nodal involvement in a real-world collective. Methods: Data collection was conducted from 2012-2024 in six certified breast cancer centers using a personal interview and data from the patients’ medical records. All patients had histologically confirmed pure DCIS or LCIS prior to mastectomy. All preoperatively diagnosed invasive breast cancer cases were excluded from final analysis. Descriptive statistics and multivariate analyzes were utilized to identify risk factors for upstaging from in situ carcinoma to invasive breast cancer. Results: The study collective included 4307 patients with primary breast cancer or in situ carcinoma. 237 preoperatively diagnosed in situ carcinomas were analyzed. 42/237 (18%) cases were upstaged to invasive breast cancer and positive lymph nodes were found in 8/237 (3%) cases. 71 cases of primary and secondary mastectomy were performed with an upstaging to invasive breast cancer occurring in 19 cases (31%). SLN biopsy in combination with mastectomy was performed in 60 patients and 3 patients with positive lymph nodes were detected. Looking into risk factors for unexpected upstaging on multivariate analyzes only a Ki67 higher then 20% was significantly correlated with an upstaging to invasive carcinoma (p = 0.033). Conclusions: The frequency of unexpected detection of invasive breast cancer in mastectomy for in situ carcinoma, is relatively low, despite comprehensive clinical work up including core needle biopsy. The likelihood of positive nodal involvement is also rather low but remains apparent and has clinical implications for adjuvant therapies. Still, postoperative and long-term complications of SLN biopsy remain an issue. Therefore, omission of SLN biopsy during mastectomy for in situ carcinoma should be discussed individually. Risk factors for upstaging need to be identified and long-term follow up is needed. Novel approaches to a two stage SLN biopsy offer surgical strategies to avoid unnecessary axillary interventions.

M. Choi, A. J. Lopes, C. M. Vargas, P. Tewari, D. S. Rouhani, R. Behnam-Hanona, J. Brown, M. Lem, A. Gozali, N. Parmeshwar, M. L. Piper; Plastic and Reconstructive Surgery, University of California, San Francisco, San Francisco, CA.

Background Fat necrosis is one of the most common complications following autologous breast reconstruction. The clinical presentation of fat necrosis can mimic that of a cancerous recurrence, inducing patient anxiety and necessitating further imaging and biopsies. Furthermore, severe cases can compromise cosmetic outcomes, often requiring revisional surgery. Despite its prevalence and clinical significance, identification of specific risk factors for the development and severity of fat necrosis is poorly understood. This study, therefore, aims to identify and examine these risk factors to improve patient outcomes. Methods We performed a retrospective review of patients who underwent autologous breast reconstruction with an abdominally based free flap at a single academic institution between September 2005 through January 2024. Data collected included demographics, surgical details, and post-operative complications (fat necrosis, infection, delayed wound healing, seroma, hematoma, necrosis, revision surgery). Chi-square and independent t-test analysis were performed to identify differences between groups, and multivariate logistic regressions were performed to assess predictors of fat necrosis. RESULTS A total of 434 patients (706 breasts) were included in this study. The median length of follow up after reconstruction was 4.2 years. 157 breasts (22%) developed fat necrosis, of which 68 breasts (43%) which underwent surgical excision. Average age (p=0.03) and BMI (p=0.01) were both significantly higher in the cohort that developed fat necrosis. Neither smoking status nor the presence of pre- or post-mastectomy radiation impacted rates of fat necrosis. Increased venous coupler size (p=0.01) and use of a bipedicled flap (p=0.000) were also significantly associated with the cohort that developed fat necrosis. Flap type (DIEP, msTRAM, SIEA) did not impact rates of fat necrosis. No significant differences in demographics or surgical details were found between patients that developed fat necrosis that did or did not warrant surgical management. On multivariate logistic regression, age (p=0.009, OR: 1.02), BMI (p=0.003, OR: 1.06), venous coupler size (p=0.04, OR: 1.58), and bipedicled flap reconstruction (p=0.00, OR: 6.05), were identified as independent predictors of developing fat necrosis. CONCLUSION This study identifies advanced age, higher BMI, the use of larger venous couplers, and bipedicled flap as independent risk factors for the development of fat necrosis following autologous breast reconstruction. These findings can help guide preoperative patient counseling and intraoperative decision-making.

T. Sakai¹, M. Ishitobi², Y. Sagara³, A. Yoshida⁴, Y. Takahashi⁵, T. Tsukioki⁵, K. Takada⁶, Y. Ono⁷, Y. Kimura¹, T. Osako⁸; ¹Breast Surgical Oncology, Breast Center, Cancer Institute Hospital of JFCR, Tokyo, JAPAN, ²Department of Breast Surgery, Osaka Habikino Medical Center, Habikino, JAPAN, ³Breast Surgical Oncology, Sagara Hospital, Hakuaikai Medical Corporation, Kagoshima, JAPAN, ⁴Breast Surgical Oncology, St. Luke’s International Hospital, Tokyo, JAPAN, ⁵Breast Surgical Oncology, Okayama University Hospital, Okayama, JAPAN, ⁶Department of Breast Surgery, Osaka Metropolitan University, Osaka, JAPAN, ⁷Department of Radiation Oncoloty, Kyoto University, Kyoto, JAPAN, ⁸Division of Pathology, Cancer Institute of Japanese Foundation for Cancer Research, Tokyo, JAPAN.

Background: In 2014, the SSO-ASTRO consensus guidelines redefined a positive margin requiring re-excision after breast-conserving surgery (BCS) as “tumor on ink.” The adoption of this standard has been reported internationally to significantly reduce the rate of surgical re-excision for positive margins. In Japan, this definition was explicitly incorporated into the 2018 Japanese Breast Cancer Society clinical practice guidelines. To clarify changes in re-excision rates before and after guideline publication in Japan, we conducted a multicenter collaborative study. Method 1: A nationwide questionnaire survey was distributed to representatives of 521 Japanese Breast Cancer Society-accredited institutions to assess current practices related to BCS, including imaging, surgical and pathological assessment, rates of positive margins, and re-excision. Method 2: Multicenter cohort study was performed using databases from seven participating institutions, examining trends in positive margin and re-excision rates among patients undergoing BCS from 2008 to 2022. Result 1: Questionnaire Survey The questionnaire survey collected responses from 262 out of 521 Japanese Breast Cancer Society-accredited institutions, representing a response rate of 55.7%. Most institutions (60%) performed between 100 and 300 breast surgeries annually, and the majority (64%) had one or two breast surgeons. A full-time pathologist was present in 89% of the institutions, and preoperative MRI was utilized in 97% of cases for disease extent assessment. Notably, the proportion of institutions reporting a positive margin rate of 0-10% increased from 47% to 63% around 2018, reflecting a shift in clinical practice following the introduction of new guidelines. However, only 18% of institutions noted a decrease in re-excision rates after a positive margin post-2018, while 77% reported no change. Despite this, the proportion of institutions with a re-excision rate of 0-10% has increased slightly from 45% to 49% since 2018, indicating that more facilities have decreased their reoperation rates. Result 2: Multicenter Cohort Survey The multicenter cohort survey analyzed data from 18,688 cases of breast-conserving surgery performed between 2008 and 2022 across seven participating institutions. Over this period, the positive margin rate showed a consistent decline, decreasing from 10.7% in 2008-2014 to 8.8% in 2015-2018, and further to 6.9% in 2019-2022. Similarly, the re-excision rate dropped from 7.6% to 6.6% and then to 4.9% across the same intervals. Multivariate analysis identified several significant predictors of re-excision: younger patient age, diagnosis of invasive lobular carcinoma, larger tumor size, and presence of lymph node metastasis. Additionally, surgeries performed before 2014 (OR 1.34, 95% CI 1.34-1.88, P<0.001) and before 2018 (OR 1.33, 95% CI 1.10-1.60, P=0.003) were associated with a higher likelihood of re-excision compared to those performed after 2019, underscoring the impact of guideline implementation on surgical practice. Conclusions: Our findings suggest considerable diversity in the approach to BCS margin assessment among Japanese breast surgeons. Following the publication of both international and domestic guidelines regarding positive margins, a significant reduction in re-excision rates after BCS was observed in Japan. This trend was gradual, corresponding to the 2014 and 2018 consensus statements, indicating that formal guideline publication has contributed to reducing re-excision rates after breast-conserving surgery.

A. Petrovsky, M. Kurbanova, M. Frolova, V. Amosova, E. Artamonova, I. Stilidi; Breast cancer, N.N. Blokhin Russian Cancer Research Center, Moscow, RUSSIAN FEDERATION.

Introduction: Sentinel lymph node biopsy (SLNB) is the standard procedure for early breast cancer (BC), however its role in patients with locally advanced tumors (cT4N0) after neoadjuvant hormonal or chemotherapy remains a subject of discussion. The data on this type of patients is limited and the rate of false-negative results exceeds 10%/ Purpose of the study: to assess the diagnostic accuracy SLNB in patients with cT4N0M0 (ycN0) breast cancer after neoadjuvant therapy. Materials and methods: Our single-center prospective cohort study included 50 consecutive patients with cT4N0M0 breast cancer who received NALT followed by mastectomy with SLNB followed by level I-II axillary lymph node dissection (ALD). A radioguided method (99mTc-albumine nano colloid) was used to identify sentinel lymph nodes. The detection rate of sentinel lymph nodes, the level of false-negative results (FNR), sensitivity, and negative predictive value were evaluated. The univariate regression analysis was conducted to determine the factors that affect the frequency of false-negative results. Results: The detection rate was 96% (48/50). Metastatic lymph nodes were detected in 15 of 48 patients 31.3% during SLNB. After ALD metastasis were detected in 19 of 48 patients (39,5%). False negative rate (FNR) was 8,3% it the cohort. Sensitivity was 82,6%, Specificity 100%, and negative predictive value was 91,5%. Total accuracy was 92,3%. If 1 or 2 sentinel lymph nodes were removed FNR was 30,8% (4/13), if 3 or more lymph nodes were detected, FNR was 0% (0/35) (p=0,012). In univariate regression analysis only in the number of removed SLN increases the frequency of FNR. Patient’s age, BMI, molecular subtype, tumor grade, type of neoadjuvant therapy (chemo/hormonal) didn’t affect the accuracy of SLMB. Conclusion: The radioguided SLMB demonstrates acceptable diagnostic accuracy in patients with cT4N0 breast cancer after neoadjuvant therapy, which allows it to be an alternative to ALD, if at least three SLN are removed.

Z. Juan¹, H. Cai¹, Y. Liang²; ¹Breast surgery, Tangshan People’s Hospital, Tangshan, CHINA, ²Ultrasound, Tangshan People’s Hospital, Tangshan, CHINA.

Efficacy and safety of intercostal nerve anastomosis in immediate biplane breast reconstruction after nipple-areola-sparing mastectomy: a randomized, controlled, open-label clinical study AbstractPurpose: to investigate the efficacy and safety of intercostal nerve anastomosis among breast cancer patients who undergo immediate biplane breast reconstruction after nipple-areola-sparing mastectomy.Methods: From 2023 to 2025, 20 to 60 year-old female breast patients (stage I-IIIA), who required and were willing to undergo immediate biplane breast reconstruction after nipple areola-sparing mastectomy, were screened and assigned to take the operation with (treatment group) or without (control group) intercostal nerve anastomosis (selected and dissociated the nerves with appropriate length and thickness among the 2nd to 4th intercostal nerves, then anastomosed to the posterior areola tissue). A radial incision at the surface projection of the tumor location was used. Using Semmes-Weinstein monofilaments to evaluate the patients’ breast local before the operation as well as at 15 days, 3 months, and 6 months postoperatively. Additionally, the patients’ quality of life was subjectively assessed using the BREAST-Q scale at 6 months after surgery. Adverse events, operation duration, drainage volume, and the duration of drainage tube carrying time were also monitored and recorded.Results: Compared to the control group, intercostal nerve anastomosis significantly improved the local sensation at 15 days, 3 months, and 6 months postoperatively (P<0.001). Along with the time an improvement was seen in the patients’ local sensation, however, we also noticed a significant decrease in local sensation in both groups (P < 0.001). Whereas the treatment group showed noticeable recovery in sensation at 3 and 6 months postoperatively, while the control group showed a significant reduction. Also, the results of the BREAST-Q scale showed that intercostal nerve anastomosis significantly improved the patients’ quality of life at 6 months postoperatively (P<0.001). Two groups held no significant differences in general characteristics (age, BMI, and subtypes). Intercostal nerve anastomosis did not affect the volume or duration of postoperative drainage tube usage, while it did increase the duration of operation by around 25 min (P < 0.001).Conclusion: This study demonstrates intercostal nerve anastomosis improved the local sensation and quality of life of patients who underwent immediate biplane breast reconstruction after nipple-areola sparing mastectomy.

V. N. Sarli¹, S. Meas¹, M. Kai², M. Desai¹, N. Erry¹, S. X. Sun³, H. M. Johnson³, W. A. Woodward⁴, A. Lucci³; ¹Breast Surgery Research, UT MD Anderson Cancer Center, Houston, TX, ²Breast Medical Oncology, UT MD Anderson Cancer Center, Houston, TX, ³Breast Surgical Oncology, UT MD Anderson Cancer Center, Houston, TX, ⁴Breast Radiation Oncology, UT MD Anderson Cancer Center, Houston, TX.

Background: Our institution has a specialized Inflammatory Breast Cancer (IBC) clinic (SIBCC) where almost all patients undergo trimodality therapy. Surgical management for IBC at SIBCC routinely consists of modified radical mastectomy to negative margins along with an axillary lymph node dissection after completion of neoadjuvant systemic therapy. We sought to evaluate the differences in surgical outcomes between patients who underwent surgery at SIBCC versus patients who underwent surgery at outside institutions (OSI). Methods: A retrospective analysis was performed on patients with IBC enrolled in a prospective registry from 2003-2025 at SIBCC. All patients underwent surgery for primary tumor removal either at SIBCC or an outside institution. Chi-squared test and Kaplan-Meier method were used for statistical analysis. Results: Of the 920 patients included, 620 had their surgical procedures completed at SIBCC, while 300 had surgery at OSI. Patients underwent the following surgical procedures: modified radical mastectomy (SIBCC: 620, 100%; OSI: 249, 83%), total mastectomy (SBICC: 0; OSI: 35, 11.7%), skin sparing mastectomy (SIBCC: 0; OSI: 5, 1.7%), and segmental mastectomy (SIBCC: 0; OSI: 5, 1.7%). Axillary lymph node dissections were performed in 96% of cases at SIBCC and 83% of cases at OSI. Pathologic nodal positivity was higher in the OSI group (40%) compared to the SIBCC group (31% p=0.021). Patients treated at outside institutions were significantly more likely to have positive surgical margins (63.2%) compared to those treated at SIBCC (2.5%, P<0.001). Median number of lymph nodes removed was higher at SIBCC (20 vs 11) (p<0.001). Of the 620 patients who completed surgery at SIBCC, 40% had a recurrence or progression, while 72% of surgical cases completed outside (216/300) had a recurrence or progression. Median overall survival was significantly longer among patients treated at SIBCC compared to those treated at OSI (153 vs 56 months, 95% CI: 141.2-164.8 vs 48.5-63.5). Similarly, patients treated at SIBCC had significantly improved relapse-free survival compared to those treated OSI (median RFS: 108 vs 16 months; p < 0.001). Locoregional recurrence-free survival was significantly longer in patients treated at SIBCC compared to those treated at OSI (mean 185.8 months vs. 92.0 months, p<0.001), highlighting the critical role of specialized surgical care in improving local disease control in IBC. Conclusion: Patients with inflammatory breast cancer had better outcomes when their surgery was performed at a specialized IBC clinic. This study demonstrated that a specialized surgical approach is associated with significantly lower rates of positive margins and improved locoregional recurrence-free survival.

T. Nakayama¹, R. Nakamura², T. Onishi³, H. Yasojima⁴, J. Ando⁵, H. Jinno⁶, T. Ogawa⁷, T. Aihara⁸, H. Matsumoto⁹, N. Masuda¹⁰, M. Kawada¹¹, S. Kuba¹², Y. Shinden¹³, N. Wada¹⁴, M. Kitada¹⁵, M. Saito-Oba¹⁶, J. Sakamoto¹⁷, S. Imoto¹⁸; ¹Breast and Endocrine Surgery, Osaka International Cancer Institute, Osaka, JAPAN, ²Breast Surgery, Chiba Cancer Center, Chiba, JAPAN, ³Breast Surgery, National Cancer Center Hospital East, Kashiwa, JAPAN, ⁴Breast Surgery, National Hospital Organization Osaka National Hospital, Osaka, JAPAN, ⁵Breast Surgery, Tochigi Cancer Center Hospital, Utsunomiya, JAPAN, ⁶Breast Surgery, Teikyo University Hospital, Tokyo, JAPAN, ⁷Breast Center, Mie University Hospital, Tsu, JAPAN, ⁸Breast Surgery, Aihara Hospital, Minoh, JAPAN, ⁹Breast Surgery, Osaka International Cancer Institute, Kitaadachi-gun, JAPAN, ¹⁰Breast Surgery, Kyoto University Hospital, Kyoto, JAPAN, ¹¹Breast and Thoracic Surgery, Tonan Hospital, Sapporo, JAPAN, ¹²Breast and Endocrine Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JAPAN, ¹³Breast and Thyroid Surgery, Kagoshima University Hospital, Kagoshima, JAPAN, ¹⁴Surgery, Tokyo Dental College Ichikawa General Hospital, Ichikawa, JAPAN, ¹⁵Breast Surgery, Asahikawa Medical University Hospital, Asahikawa, JAPAN, ¹⁶Clinical Research ＆ Education Promotion Division, National Center of Neurology and Psychiatry, Tokyo, JAPAN, ¹⁷Clinical Research Department, Tokai Central Hospital, Kakamigahara, JAPAN, ¹⁸Breast Surgery, Kyorin University Hospital, Hachioji, JAPAN.

Background: Sentinel node biopsy (SNB) has been the standard of care for patients with clinically node-negative breast cancer (BC) since the 2000s. Recent ASCO guidelines now permit SNB to be omitted under specific conditions in clinical T1N0 BC. While axillary lymph node dissection (ALND) remains a regional control option for early BC, optimal axillary management, including repeat SNB, for ipsilateral breast tumor recurrence (IBTR) remains undefined. To address this, the Japanese Society for Sentinel Node Navigation Surgery (SNNS), established in 1999 to advance sentinel node research in solid tumors, conducted a retrospective cohort study (UMIN No. 000049737) on axillary management in IBTR cases. Patients and Methods: We included patients with clinical Tis-4N0 BC who underwent partial mastectomy and SNB, and whose IBTR was diagnosed between January 2010 and August 2022. Exclusion criteria included clinically node-positive BC, bilateral BC, and stage IV BC. Adjuvant therapy decisions were at the physician’s discretion. We analyzed clinicopathological data, focusing on lymphatic mapping and repeat SNB, from primary BC and IBTR medical records. This study received approval from the Kyorin University School of Medicine institutional review board. Results: Our study enrolled 314 eligible cases from 20 Japanese institutions. At primary BC diagnosis, 66 cases were stage 0, 178 were stage IA/B, 66 were stage IIA/B, 1 was stage IIIA, and 3 had unknown stages. SNB was successful in 312 cases (99.3%), with only 12 cases (3.8%) showing positive sentinel lymph nodes (SLN). Breast and regional nodal irradiation were performed in 237 and 8 cases, respectively. IBTR was diagnosed between 3 and 259 months (median: 70 months) after primary BC surgery. Total mastectomy was planned for 243 cases, and partial mastectomy for 64. Sixteen cases also underwent breast reconstruction. Repeat SNB was performed in 216 cases (68.7%), with successful SLN identification in 181 (83.7%). Of the 168 cases that underwent radioisotope-guided lymphatic mapping, hot spots were visualized in 112 (66.6%) via lymphoscintigraphy. SLN localization showed 175 in the ipsilateral axilla, 6 in the contralateral axilla, and 4 in the ipsilateral internal mammary lesion. Positive SLN rates were 9.1% (11 cases) for ipsilateral axilla, 1.6% (1 case) for contralateral axilla, and 0% (0 cases) for ipsilateral internal mammary lesion. Following axillary management for IBTR, repeat SNB was performed in 194 cases (61.7%), lymph node sampling in 2 (0.6%), ALND in 37 (11.7%), and no axillary surgery in 81 (25.7%). Post-IBTR axillary management, 20 cases experienced regional or contralateral lymph node recurrence, and 23 cases died. Conclusion: Repeat SNB is feasible and provides valuable information for de-escalation surgery in IBTR cases. However, axillary management should be carefully considered, taking into account both loco-regional and systemic dissemination at the time of IBTR diagnosis.

H. Seki¹, T. Komiya², M. Kato³, Y. Sowa⁴, J. Takano⁵, Y. Nishida¹, N. Tamura⁶, M. Saiga⁷; ¹Breast Surgery, Kyorin University School of Medicine, Tokyo, JAPAN, ²Plastic and Reconstructive Surgery, Tokyo Medical University, Tokyo, JAPAN, ³Plastic Surgery, Aichi Medical University Hospital, Aichi, JAPAN, ⁴Plastic Surgery, Jichi Medical University, Tochigi, JAPAN, ⁵Plastic Surgery, Saitama Medical Center, Saitama, JAPAN, ⁶Breast and Endocrine Surgical Oncology, Toranomon Hospital, Tokyo, JAPAN, ⁷Plastic Surgery, Okayama University Hospital, Okayama, JAPAN.

Background: Surgical decision-making in breast cancer involves not only clinical and oncological considerations but also psychosocial factors such as personal values, social support, and anticipated quality of life. Although shared decision-making (SDM) is increasingly emphasized, factors influencing patients’ surgical choices remain unclear. This study aimed to identify determinants associated with the selection of total mastectomy (MT), breast-conserving surgery (BCS), or immediate breast reconstruction (IBR) using patient-reported outcomes. Patients and Methods: A multicenter study was conducted across six institutions in Japan. We included 577 female patients who underwent breast cancer surgery between 2008 and 2018. Using patient-reported outcomes, we collected data on sociodemographic background and 15 decision-influencing factors, including opinions of healthcare providers, family, and peers; radiation therapy; fear of recurrence; hospitalization; and perceived impacts on childcare, work, and hobbies. Patients were categorized into MT, BCS, or IBR groups. Chi-square tests were used for group comparisons, and multinomial logistic regression was performed using the IBR group as the reference. Results: Among 577 patients, 194 underwent MT, 185 BCS, and 198 IBR. The mean age was 53.6 years (±11.5), with the IBR group significantly younger (48.2) than MT (58.1) and BCS (54.8) (p<0.001). The mean interval from surgery to questionnaire response was 56.0 months. IBR patients were more likely to have avoided chemotherapy (p<0.001), be non-smokers (p<0.001), have smaller tumors (p<0.001), no nodal metastasis (p=0.003), and be full-time employed (p<0.001). The incidence of postoperative complications (grade ≥3) was highest in the IBR group (p<0.001). The most reported influence was the surgeon’s opinion (92.2%), followed by fear of recurrence (43.8%), partner’s opinion (35.5%), family (22.4%), and breast cancer survivors (21.0%). Patients influenced by nurses were more likely to select IBR (MT: 3.1%, BCS: 4.5%, IBR: 10.8%; p=0.004). Other significant differences included partner’s opinion (p=0.012), hospitalization (p=0.022), radiation therapy (p<0.001), recurrence fear (p=0.002), and concerns about hobbies (p=0.004) and work (p=0.025). Univariable analysis showed that IBR was more likely in patients who were younger (p<0.001), had smaller tumors (p<0.001), no nodal metastasis (p=0.036), no chemotherapy (p=0.007), were non-smokers (p=0.001), employed full-time (p<0.001), and had higher income (p=0.004). IBR was also associated with influence from nurses (p=0.005), partners (p=0.005), hospitalization (p=0.009), hobbies (p=0.017), and work concerns (p=0.011). Recurrence fear was associated with higher IBR selection over BCS (p=0.017). In multivariable analysis, independent predictors of selecting IBR over both MT and BCS included younger age (p<0.001), non-smoking status (p=0.012), being influenced by nurses’ opinions (p=0.022), and absence of fear of cancer recurrence (p=0.042). Conclusions: This study is the first large-scale, multicenter collaborative study to identify factors influencing surgical decision-making in Japanese breast cancer patients. Predictors influencing the choice of IBR compared with MT and BCS were age, smoking status, nurses’ opinions, and anxiety about recurrence. The results of this study suggest the importance of multidisciplinary collaboration and surgical decision-making support that considers the individual background of patients.

B. A. Engelman¹, Y. L. Eaglehouse², S. Darmon², M. Nealeigh², R. W. Krell², C. D. Shriver², K. Zhu²; ¹General Surgery, Landstuhl Regional Medical Center, Landstuhl, GERMANY, ²Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD.

Background: Obesity is known to increase risk of postoperative complications for patients undergoing general and cardiovascular surgery. The impact of obesity on risk of complications among women with breast cancer is less understood. Access to medical care may be associated with management of obesity and its related conditions, as well as in the diagnosis and treatment of cancer. Thus, it is unknown what the association between obesity and risk of short-term complications and readmission after breast cancer surgery is when controlled for access to medical care. To address this gap in knowledge, we aimed to study the association of obesity with risk of general and breast-specific complications among women with breast cancer in the U.S. Military Health System which provides access to care for all eligible Department of Defense beneficiaries with little financial barriers. Methods: Women aged 18 and older with non-metastatic invasive breast cancer between 2001 and 2014 and who underwent breast conservation or total mastectomy without immediate reconstruction were included. Obesity status was determined by the presence of International Classification of Diseases (ICD)-9^th edition diagnosis codes corresponding to body mass index (BMI) greater or equal to 30 in the medical encounter data prior to breast cancer diagnosis. General and breast surgery-specific complications, breast reoperation, and hospital readmissions were assessed in the 30-day postoperative period. Modified Poisson regression was used to compare the risk of the outcomes between women with and without obesity expressed as adjusted risk ratios (ARRs) with 95% confidence intervals (CIs). Results: The study included n=1,094 women with obesity (mean age 57.5 +/-10.9 years) and n=6,741 women without obesity (mean age 55.9 +/-13.0 years) receiving surgery without immediate reconstruction for stage I-III breast cancer. Overall, the frequency of general complications was 2.5% among women with obesity and 1.9% among women without obesity (Chi-square p=0.22). The risk of general complications (e.g. myocardial infarction, pneumonia) was not statistically different by obesity status (ARR=0.95, 95% CI=0.61, 1.49 for obese vs. non-obese) in multivariable analyses with adjustment for potential confounders including age, race-ethnicity, tumor stage, and total comorbidity burden. The frequency of breast-specific complications was 8.9% among women with obesity and 6.3% among women without obesity (Chi-square p=0.03). In Poisson models, women with obesity had a 29% higher risk of breast complications (ARR=1.29, 95% CI=1.03, 1.61) relative to women without obesity. For specific complications, the risk among women with obesity was higher relative to those without obesity for surgical site infection (ARR=1.56, 95% CI=1.10, 2.21) and lymphedema (ARR=1.71, 95% CI=1.02, 2.88) and not statistically different for hematoma or seroma after adjusting for patient, tumor, and surgery characteristics. There were no statistical differences in risk of reoperation (ARR=0.93, 95% CI= 0.80, 1.10) or readmission (ARR=1.04, 95% CI=0.79, 1.36). Conclusion: In the universal Military Health System, women with obesity had an increased risk of site-specific postoperative complications following breast cancer surgery, especially surgical site infection and lymphedema. Our results highlight the importance of weight management in breast surgical oncology care and indicate that efforts are needed to identify effective interventions which may reduce both obesity and risk of postoperative complications among women with breast cancer.

M. Heidinger¹, G. Montagna², F. Halbeisen³, N. Maggi¹, M. Frevert¹, R. Kiblawi¹, J. Loesch¹, F. D. Schwab¹, C. Kurzeder¹, T. A. Zwimpfer⁴, W. P. Weber¹; ¹Breast clinic, University Hospital Basel, Basel, SWITZERLAND, ²Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, ³Surgical Outcome Research Center, University Hospital Basel, Basel, SWITZERLAND, ⁴Gynaecology & Obstetrics, University Hospital Basel, Basel, SWITZERLAND.

Introduction The SOUND and INSEMA trials included patients who underwent breast-conserving surgery (BCS). Mastectomy offers equivalent local control; however, tumor stage is often more advanced, potentially impacting adjuvant treatment decisions. Adjuvant cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) provide oncological benefits to patients with hormone receptor (HR)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC). Their indication is based on clinical parameters yet irrespective of the type of breast surgery performed. Consequently, it remains unclear whether in SOUND/INSEMA eligible patients with HR-positive/HER2-negative BC undergoing mastectomy versus BCS proportions of node-positivity differ, and whether omission of sentinel lymph node biopsy (SLNB) would impact treatment candidacy for CDK4/6i differently. Methods This single-center, retrospective cohort study included patients with clinically T1 and T2, cN0/iN0, HR-positive/HER2-negative BC who underwent SLNB between 01/2014 and 12/2024. Clinicopathological features, nodal involvement, and CDK4/6i eligibility were compared between patients who underwent mastectomy and BCS. CDK4/6i eligibility was evaluated using the monarchE (≥4 positive lymph nodes, or 1-3 positive lymph nodes and either grade 3 disease, tumor size ≥5cm, or Ki67 ≥20%) and NATALEE inclusion criteria. Ribociclib eligibility based on node-criteria was defined as either pT1pN1 (excluding pN1mi) or pT2pN1, provided that no additional criteria would render the pT2 status per se eligible for treatment. Multivariable logistic regression analysis was used to identify independent predictors of node-positivity and CDK4/6i eligibility. Results A total of 454 patients were included, of whom 31.9% (145/454) underwent a mastectomy. Patients who underwent a mastectomy had clinically larger tumors (cT2 37.2% vs. 27.8%, p=0.05) without differences in pathological tumor stage (p=0.185). Tumors of patients who underwent a mastectomy were more frequently multifocal (23.5% vs. 9.7%, p<0.001), of lobular histotype (21.4% vs. 11.3%, p=0.008), and exhibited a higher tumor grade (grade II and III 73.8% vs. 63.8%, p=0.019). The median number of positive lymph nodes was comparable between groups (0, IQR 0-0 vs. 0, IQR 0-0, p=0.283) without differences in pathological nodal stage (pN1 16.6% vs. 14.6%, p=0.168). Predictors of node-positivity were found to be lymphovascular invasion (odds ratio [OR] 6.8, 95%CI 3.7-12.9, p<0.001) and premenopausal status (OR 2.0, 95%CI 1.0-3.8, p=0.034). Mastectomy was not found to be a predictor of node-positivity (OR 1.1, 95%CI 0.6-1.9, p=0.719).Eligibility for any CDK4/6i was numerically higher in patients who underwent a mastectomy (29.7% vs. 21.4%, p=0.06). However, eligibility based on nodal criteria did not show any differences between the groups (abemaciclib 7.6% vs. 6.2%, p=0.550; ribociclib 9.7% vs. 7.8%, p=0.586). Predictors for CDK4/6i eligibility were found to be ≥pT2 (OR 12.9, 95%CI 6.5-26.5, p<0.001), Ki67 ≥20% (OR 5.3, 95%CI 2.9-10.0, p<0.001), and lymphovascular invasion (OR 5.1, 95%CI 2.6-10.1, p<0.001). Mastectomy was not found to be a predictor of CDK4/6i eligibility (OR 1.3, 95%CI 0.7-2.3, p=0.481). Conclusion In patients with cT1-T2, cN0/iN0, HR-positive/HER2-negative BC, type of surgery did neither impact node positivity nor CDK4/6i eligibility. These findings support the consideration of SLNB omission in appropriately selected patients undergoing mastectomy, particularly postmenopausal women with low-risk tumors. Further investigation of the extension of SLNB omission eligibility to patients undergoing mastectomy is warranted.

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

BackgroundNipple-sparing mastectomy (NSM) is increasingly utilized in breast cancer surgery due to its superior cosmetic outcomes and patient satisfaction. However, ischemic complications, particularly necrosis of the nipple-areolar complex (NAC), remain a significant concern, with reported incidence ranging from 6% to 30%. Several patient- and surgery-related factors such as large breast volume, periareolar incisions, prior breast surgery, radiation exposure, and smoking have been identified as contributors to NAC necrosis. Nipple delay (ND) is a surgical technique performed approximately 1-2 weeks prior to NSM, designed to improve NAC perfusion and reduce ischemic complications in patients considered high risk. While the efficacy of ND has been demonstrated in Western populations, there are no published studies evaluating this technique in an Asian population. To our knowledge, this is the first report from Japan to assess the impact of ND in a cohort of Japanese patients undergoing NSM with immediate autologous reconstruction. Methods We conducted a retrospective review of patients who underwent either ND followed by NSM (ND-NSM) or NSM alone between January 2020 and March 2025 at a single high-volume breast cancer center in Japan. All patients underwent one-stage autologous breast reconstruction using abdominal flaps. ND was performed approximately 14 days prior to NSM under local or general anesthesia, using a semicircular periareolar incision and skin undermining to precondition the NAC. Baseline characteristics, including body mass index (BMI), history of breast surgery, radiation therapy, and smoking status, were collected. Surgical variables such as incision type, mastectomy specimen weight, and postoperative complications were analyzed. NAC necrosis was graded by severity, and statistical comparisons were performed using Fisher’s exact test or Mann-Whitney U test, as appropriate. Results A total of 100 patients were included, with 31 in the ND-NSM group and 69 in the NSM-only group. There were no significant differences between the two groups in terms of BMI, prior breast surgery, radiation exposure, or smoking history. The ND-NSM group had a significantly higher frequency of periareolar incisions (73.5% vs. 33.3%, p < 0.01) and larger mastectomy weights (median 350g vs. 275g, p = 0.02), indicating higher surgical risk. The overall incidence of NAC necrosis did not differ significantly between groups (22.6% in ND-NSM vs. 23.2% in NSM-only). However, when stratified by necrosis grade, the ND-NSM group demonstrated a significantly lower rate of grade ≥2 necrosis (p = 0.0276). Importantly, no cases of grade ≥2 necrosis were observed in the ND group. Other complications such as skin necrosis, infection, thrombosis, and flap-related events were similar between groups. Conclusion Despite higher-risk features, the ND-NSM group showed a markedly reduced severity of NAC necrosis. Our findings suggest that the nipple delay procedure may allow patients with traditionally high-risk characteristics to safely undergo NSM with complication rates comparable to lower-risk patients. This is the first study from Japan to evaluate the clinical utility of ND, and our results indicate that this approach is both feasible and beneficial in the Japanese population. ND should be considered a valuable adjunct to NSM in patients at elevated risk for ischemic complications, particularly when immediate autologous reconstruction is planned.

G. Tosello¹, R. Riera², M. Torloni², T. Neeman³, M. Cruz⁴, I. Freitas⁵, D. Christofaro⁵, T. Paulo⁶, C. Oliveira⁷, B. Mota⁸; ¹Gynecology and Obstetrics, Unoeste, Presidente Prudente, BRAZIL, ²Adjunct Professor of Evidence-Based Medicine at Escola Paulista de Medicina UNIFESP, Unifesp, Sao Paulo, BRAZIL, ³Statistics Department, Australian National University, Canberra, AUSTRALIA, ⁴Medical Oncology, Hospital Sírio-Libanês, Sao Paulo, BRAZIL, ⁵Department of Physical Education, Unesp, Presidente Prudente, BRAZIL, ⁶Department of Physical Education, Universidade Federal do Rio Grande do Norte, Natal, BRAZIL, ⁷Department of Medicine, Unoeste, Presidente Prudente, BRAZIL, ⁸Gynecology and Obstetrics, ICESP FMUSP, Sao Paulo, BRAZIL.

TitleBreast surgery for metastatic breast cancer a update of Cochrane systematic review.ObjectivesTo assess the effects of breast surgery on women with de novo metastatic breast cancer.MethodologyThe inclusion criteria were randomized controlled trials of women with de novo metastatic breast cancer that compared breast surgery plus systemic therapy versus systemic therapy alone in these databases: the Cochrane Breast Cancer Specialised Register, CENTRAL, MEDLINE (by PubMed), and Embase (by OvidSP) on 19 April 2023. The primary outcomes were overall survival (OS) and quality of life. Secondary outcomes were progression-free survival (local and distant control) and toxicity from local therapyTwo review authors independently conducted trial selection, data extraction, and ‘Risk of bias’ assessment (using Cochrane’s ‘Risk of bias’ tool), which was checked by a third review author. We used the GRADE tool to assess the quality of the body of evidence, the risk ratio (RR) to measure the effect of treatment for dichotomous outcomes, and the hazard ratio (HR) for time-to-event outcomes. We also calculated the 95% confidence intervals (CI) for these measures. We used the random-effects model, as we expected clinical or methodological heterogeneity, or both, among the included studies. We reported continuous outcomes, including quality of life, as mean differences (MD) with 95% CIs. We planned to use standardised mean differences (SMD) if outcomes were reported on different scales. ResultsThis is an update of the Cochrane systematic review published in 2018, which was approved by the ethics committee and had its research protocol published in 2014.We included five randomized clinical trials including 1368 women with de novo metastatic breast cancer in the review. Breast surgery not reduce mortality in women with de novo metastatic breast cancer (HR 0.89; 95% CI 0.75 to 1.05, P = 0.09; 5 studies, 1368 participants; I2 = 50%; moderate certainty of evidence). In subgroup analyses of overall survival for women with luminal tumours, the addition of breast surgery to systemic treatment appears to increase the OS, reducing the risk of death by 18% (HR 0.82; 95% CI 0.69 to 0.96; 4 studies; 841 women; P = 0.72; I2 = 0%; moderate certainty of evidence). Breast surgery reduces the risk of local disease progression (HR 0.43; 95% CI 0.32 to 0.58; 4 studies; 1093 women; I2 = 31%; high certainty of evidence) and doesn’t improve metastatic disease control (HR of 1.19, 95% CI 0.86 to 1.18; 3 studies; P = 0.29; I2 = 69%; moderate certainty of evidence). The quality of life of women undergoing locoregional treatment is similar when compared to women undergoing systemic treatment alone in 24 months of follow-up (MD 2.74; 95% CI -2.22–7.70, I2 =0%, p = 0.28, 2 studies, low certainty of evidence). Overall survival Overall survival (Luminal subgroup analysis)Local progression-free survivalConclusionsEvidence from five randomised controlled trials suggests that adding breast surgery to the treatment of de novo metastatic breast cancer improves local disease control. The impact on survival may vary depending on the immunohistochemical profile of the tumour. Breast surgery might not affect quality of life, toxicity and distant progression-free survival.

C. Gavisiddappa, R. Parmeshwar, P. McManus, S. Somasundaram; Breast Surgery, University Hospitals of Morecambe Bay NHS Foundation Trust, Lancaster, UNITED KINGDOM.

Retrospective analysis of axillary recurrence in patients with breast cancer receiving radiotherapy to the axilla after positive sentinel lymph node biopsy Background: Breast cancer surgery currently focuses on de-escalating treatment without compromising oncological safety. Axillary lymph node dissection (ALND) has been the standard of care in all sentinel lymph node biopsy (SLNB) positive patients. Although axillary lymph node dissection provides excellent regional control, there are additional side effects like lymphoedema, shoulder stiffness, numbness in the arm. Studies show axillary radiotherapy is an alternate and equally effective treatment for SLNB-positive patients with reduced morbidity. However, this is not a standard of practice in all breast centers in UK. Methodology: A retrospective, single center study between June 2015 and June 2022 following the results published from AMAROS (After Mapping of the Axilla: Radiotherapy Or Surgery) trial in 2014. All patients with breast cancer and clinically and radiologically negative axilla underwent SLNB along with either breast conserving surgery or mastectomy as a routine procedure. Patients with positive SLNB were later offered further axillary management (ALND vs Axillary radiotherapy). Patients who opted for axillary radiotherapy were then analyzed in a retrospective study. Patients’ demographics, disease distribution, nodal positivity, adjuvant treatment were studied. The primary end point was axillary recurrence at the end of 5 years (in line with the AMAROS trial i.e. not more than 4% in axillary radiotherapy group). The secondary end point was arm morbidity and overall survival. Results: A total of 186 patients had positive sentinel lymph node biopsy during the study period and out of them 112 patients, opted for axillary radiotherapy as their mainstay of axillary management. 40(35.7%) patients had T1 disease, 57(50.89%) patients had T2, and 15(13.39%) patients had T3 disease. 13.39% had Grade1 disease, 53.57% had Grade2, and 33.92% had Grade 3 disease. The median number of nodes being 1. The mean age was 63 years, and the mean tumor size of 14.33mm. The mean follow-up was 5.58 years. Axillary recurrence was seen in 3 patients (2.67%), and 1 patient (0.89%) developed lymphedema. 9 patients (8.03%) had distant metastasis. Death due to breast cancer was slightly lower in our study as compared to AMAROS trial (7.84% vs 10.3%) and similar overall death rates (19.04% vs 16.4%) Conclusion: Our study shows that the 5-year axillary recurrence rate is comparable with the AMAROS trial (2.76% vs 1.19%) with similar follow up period (5.58years vs 6.1years). Our study has limitations of small numbers but aligns well with the AMAROS trial. Hence, axillary radiotherapy is non-inferior to axillary lymph node dissection in patients with positive SLNB with significantly less morbidity.

S. N. Virji, L. Vohra, S. Khan, I. Khan; Breast Surgery, Department of Surgery, Aga Khan University Hospital, Karachi, Karachi, PAKISTAN.

Background: Surgical management has greatly evolved from a radical mastectomy to the most recent advancement of a more conservative oncoplastic breast surgery (OBS). It has not only proven to be safe, but also has shown superior cosmetic outcomes compared to standard breast conservation surgery as it is able to address larger and even multi-focal tumors. Nevertheless, this is a relatively novel concept in our developing country with a limited number of professionals trained in the field. Furthermore, there is a financial aspect and stigma to take into consideration. Patients have to pay out of pocket for treatment which deters them from risking the possibility of a second surgery – incase of incomplete resection margins. It also adds the burden on the surgeon to deliver optimal cosmetic outcomes with no intervention to the contralateral breast. The purpose of this study is to determine the long-term oncological and cosmetic outcomes of patients with early-stage breast cancer who underwent OBS at our institution. Methodology: A single-center retrospective study was conducted on adult female patients with biopsy proven Stage I to III breast cancer who underwent OBS from January 2017 to June, 2022. Patients who underwent bilateral breast surgery were excluded. A total of 194 women were eligible for the study and data was extracted from patient records to determine the long term oncologic outcomes— breast cancer recurrence, disease-free survival (DFS), and overall survival (OS). Cosmetic outcomes were evaluated via patient-reported satisfaction using the Harvard breast cosmesis scale, through telephonic interview after obtaining informed verbal consent. The study was approved by the institutional Ethical Review Committee (ERC 2025-11482-34955). Results: The mean age of women at diagnosis was 48.3 ± 13.2 years with 81% having invasive ductal carcinoma. Sixty-seven percent of the women had hormone receptor positive breast cancer, while 20% had triple negative disease. Among all the patients who were included in the study, half of the patients received neoadjuvant chemotherapy before OBS, followed by adjuvant radiation therapy. Of note, only 6 (3.1%) out of 194 women had a positive margin for which they underwent a second procedure. Level 1 OBS was performed among 77% of the patients. Among those who underwent Level 2 OBS a variety of local perforator flaps were performed. We had a 68% response rate among the patients who were approached via telephone to determine the self-reported cosmetic outcomes, with 91% of the participants reporting ‘Good’ (51%) or ‘Excellent’ (40%) cosmetic outcomes when compared to the contralateral breast. Eight (4.1%) out of 16 patients had an ipsilateral recurrence, while the remaining developed distant metastases. The Kaplan Meier analysis showed that the mean OS of the study participants was 96 months (95% CI=92.2-99.7) since diagnosis, with death as the outcome event. The mean DFS was 93 months (95% CI=89.5 – 97.6) since diagnosis until recurrence as the outcome event. There were significant differences in survival times for patients by recurrence (log rank test, p=0.000) and hormone receptor status (log rank test, p=0.015). There was no significant difference in survival times for patients by type of OBS (log rank test, p=0.860). Conclusion: Oncoplastic breast surgery is a safe and effective option for early-stage breast cancer, with low margin positivity and favorable long-term outcomes. Our study demonstrates excellent survival and high patient-reported cosmetic satisfaction, especially with Level 1 OBS. These findings support its broader use—even in resource-limited settings—as a balanced approach to oncologic safety and aesthetic outcomes.

S. PARPOUDI¹, R. Iosifidou¹, C. Kontos¹, M. Paida², C. Geranou³, E. Skourtanioti³, V. Xatziravdeli⁴; ¹Surgical Breast Oncology Unit, Anticancer Hospital Theageneio, Thessaloniki, GREECE, ²Gynaecology Department, Ippokrateio General Hospital of Thessaloniki, Thessaloniki, GREECE, ³Radiology Department, Anticancer Hospital Theageneio, Thessaloniki, GREECE, ⁴Sport Medicine Department, KAT Attica General Hospital, Athens, GREECE.

Title:Evaluating the Role of Preoperative Magnetic Resonance Imaging and Intraoperative 3D Tomosynthesis in Achieving Negative Resection Margins in DCIS Introduction:The increased implementation of breast cancer screening programs has led to a rise in the detection of ductal carcinoma in situ (DCIS). This, however, has introduced new challenges in the surgical management of DCIS, particularly in achieving negative resection margins. The impact of preoperative breast magnetic resonance imaging (MRI) on reducing reoperation rates remains debatable. Furthermore, the use of intraoperative 3D tomosynthesis (3D mammography) to assess surgical specimens presents a potential method for ensuring margin adequacy during surgery. Materials and Methods:From 2017 to 2024, a total of 280 patients diagnosed with DCIS were treated at the Breast Surgical Oncology Department of Anticancer Hospital Theagenio. Among them, 87 were women under 50 years of age and 193 were over 50. The study examined DCIS grade (1, 2, 3), mammographic breast density (ACR categories A-D), and family history. Patients were categorized based on whether they underwent preoperative breast MRI and whether 2D or 3D tomosynthesis was used on the surgical specimen. Reoperation rates were then compared across these groups. Results:Out of the 280 patients, 136 did not undergo preoperative breast MRI, while 144 did. Reoperations were required in 16 patients without MRI and 9 with MRI. Although the overall analysis showed no statistically significant association between MRI use and reoperation rate, age and breast density were significantly correlated with reoperation rates (p=0.018 and p=0.001, respectively). Subgroup analysis revealed that breast density and MRI use significantly influenced reoperation outcomes (p=0.001 and p=0.005, respectively). Additionally, the use of intraoperative 3D tomosynthesis was significantly associated with achieving negative margins (p=0.002). Conclusions:Preoperative breast MRI did not significantly reduce reoperation rates across the entire patient cohort. However, it showed beneficial effects in younger women with dense breast tissue. Intraoperative use of 3D tomosynthesis also contributed to improved surgical outcomes. The combination of these two modalities may represent an effective strategy for reducing reoperation rates in the treatment of DCIS. Keywords: DCIS, breast MRI, intraoperative 3D tomosynthesis, surgical margins, reoperation.

R. Macedo Sousa Rahal¹, H. Garcia Gomes de Andrade¹, L. Pádua Oliveira¹, D. Calheiros Campelo Maia², F. Cardoso Marques³, C. Dias Caminha Gentile⁴, M. Macambira Noronha⁵, P. Costa Passos⁴, V. Oliveira Costa Filho⁴; ¹DEPARTMENT OF GYNECOLOGY, UNIVERSIDADE FEDERAL DE GOIAS, Goiania, BRAZIL, ²DEPARTMENT OF CLINICAL ONCOLOGU, HOSPITAL UNIVERSITÁRIO WALTER CANTIDIO, Fortalez, BRAZIL, ³UNDERGRADUATE, UNIVERSIDADE FEDERAL DO CEARÁ, Goiania, BRAZIL, ⁴UNDERGRADUATE, UNIVERSIDADE FEDERAL DO CEARA, FORTALEZA, BRAZIL, ⁵UNDERGRADUATE, UNIVERSIDADE FEDERAL DO CEARÁ, Fortaleza, BRAZIL.

Introduction: Breast cancer (BC) remains the most common malignancy among women and is the fourth leading cause of mortality worldwide. Despite advances in screening, surveillance, and treatment that have improved survival rates, most patients continue to experience treatment-related adverse effects that significantly impact their quality of life(QoL). Objective: This study aims to describe the prevalence and risk factors associated with chronic pain, as well as its impact on QoL, in patients with BC treated at a single institution in Brazil. Methodology: This cross-sectional study included patients with BC who received treatment in the mastology department of Hospital das Clínicas da Universidade Federal de Goiás, Brazil in 2022. Data collected included clinical characteristics (age, menopausal status, comorbidities) and treatment characteristics (type of surgery, radiotherapy, chemotherapy, and treatment toxicity). Standardized questionnaires assessing chronic pain, such as the McGill Pain Questionnaire and the Visual Analogue Scale (VAS), were administered. Statistical analyses were performed using R Studio v 3.6, employing descriptive statistics, Pearson correlation, and regression analyses to evaluate the study data. Results: 122 patients were included in the analysis, with a median age of 55 years. 84% were postmenopausal. Breast reconstruction was performed in 53% of the patients, the majority of whom (92%) underwent immediate reconstruction. Regarding systemic therapy, 51% of patients received neoadjuvant chemotherapy and 29% received adjuvant chemotherapy. Additionally, 81% of the patients received radiotherapy. Lymphedema was present in 20% of the cohort and seroma was reported in 15% of all patients. The total McGill score had a median of 30 (IQR: 22-38). On the Visual Analogue Scale, the median pain intensity was 5.5 (IQR: 3-8). We conducted Wilcoxon rank-sum tests to assess whether pain intensity, measured by the VAS scale, varied according to clinical and treatment-related variables. Patients who underwent mastectomy reported significantly higher pain scores than those who received breast-conserving surgery (p = 0.0088). Higher VAS scores were also observed among patients with lymphedema (p = 0.0069) and those who experienced wound dehiscence (p = 0.026). Interestingly, patients who received radiotherapy reported significantly lower pain intensity compared to those who did not undergo this treatment (p = 0.016). We also examined the association between clinical characteristics and pain perception using the total score from the McGill Pain Questionnaire. Among the variables analyzed, wound dehiscence was significantly associated with higher McGill scores (p = 0.011). Conclusion: Chronic pain is highly prevalent and significantly impairs health-related quality of life in breast cancer patients treated in our cohort in Brazil, especially those with high-risk surgical profiles and comorbidities.

C. S. Vasconcelos, I. V. Araújo, M. Salgado, D. S. Viana, L. Torres, C. R. Jesus, C. C. Anunciação; Breast Cancer, Hospital Cancer of Pernambuco, Recife, BRAZIL.

AbstractTitle: Oncoplastic and Reconstructive Breast Surgery: Experience in a Public Tertiary Hospital of the Brazilian Unified Health System (SUS)Introduction: Breast cancer is the most common malignancy among women worldwide (excluding non-melanoma skin cancer) and the leading cause of cancer-related death in this population. Advances in surgical techniques have progressively shifted treatment paradigms toward breast-conserving approaches. Oncoplastic surgery merges oncologic safety with plastic surgery principles, enabling broader indications for breast conservation and enhancing aesthetic and psychological outcomes for patients.Objective: To evaluate the clinical and epidemiological profile of patients undergoing oncoplastic breast surgery with immediate or delayed reconstruction in a Brazilian public tertiary hospital, as well as to analyze postoperative complications and compare results with current literature.Methods: A cross-sectional, descriptive, and analytical study was conducted with 100 female patients who underwent oncoplastic breast surgery at the Pernambuco Cancer Hospital (HCP) between March 2023 and July 2024. Data were collected from medical records and included demographics, tumor characteristics, surgical procedures, adjuvant treatments, and postoperative complications. Statistical analysis was performed using SPSS v27 with a 5% margin of error.Results: The patients’ mean age was 50.2 years. Of the 100 cases, 59% underwent oncoplastic quadrantectomy, while 39% had mastectomy with immediate reconstruction. Only 2 patients underwent delayed reconstruction. The most common techniques included therapeutic mammoplasty (17%) and the Burrow triangle (12%). Symmetrization was performed in 29% of cases and fat grafting in 5%. The majority of tumors were stage T1 or T2 (72%) and axilla-negative (73%). Most patients were luminal subtype (61%), and 13% had in situ lesions. Systemic treatment included chemotherapy (60%), radiotherapy (64%), hormone therapy (57%), and HER2-targeted therapy (14%).Postoperative complications occurred in 14% of patients, with wound dehiscence being the most frequent (7%). Five patients required reoperation, including two prosthesis removals and three margin enlargements. No statistically significant association was found between complications and clinical variables, although patients undergoing mastectomy showed a higher absolute rate of complications compared to those who had conservative surgery (22% vs. 8.5%).Conclusion: Oncoplastic breast surgery proved to be a safe and effective strategy for both breast conservation and post-mastectomy reconstruction in a resource-limited public healthcare setting. The complication rate was low and aligned with international standards, despite the absence of plastic surgeons in most cases. The findings support the inclusion of oncoplastic training in mastology residency programs as a way to increase access to reconstruction and improve quality of life for patients treated within the public health system. This approach, beyond restoring anatomy, promotes emotional and psychological well-being, reinforcing its role as a key component in the holistic management of breast cancer. Keywords: Breast cancer; Oncoplastic surgery; Breast reconstruction; Public health; Surgical outcomes

A. Dominique Nascimento Lima¹, F. Pimentel Cavalcante², A. Mattar³, F. Pereira Zerwes⁴, M. Antonini⁵, M. Leite Kraft⁶, A. Oliveira de Alencar², A. de Queiroz Germano², D. Pitanga Torres⁷, E. Goulart Carneiro⁸, C. Freitas de Lima⁸, R. Zocchio Torresan⁶, F. Palermo Brenelli⁶, M. Lichtenfels⁹, A. Frasson⁹, J. Bines¹⁰, E. Camargo Millen⁸; ¹Breast Surgery, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BRAZIL, ²Breast Surgery, Hospital Geral de Fortaleza, Fortaleza, BRAZIL, ³Breast Surgery, Hospital da Mulher SP, São Paulo, BRAZIL, ⁴Breast Surgery, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, BRAZIL, ⁵Breast Surgery, Hospital do Servidor Público Estadual, Sao Paulo, BRAZIL, ⁶Breast Surgery, Universidade Estadual de Campinas, Campinas, BRAZIL, ⁷Breast Surgery, Instituto Américas – Ensino, Pesquisa e inovação, Rio de Janeiro, BRAZIL, ⁸Breast Surgery, Instituto Americas – Ensino, pesquisa e inovação, Rio de Janeiro, BRAZIL, ⁹Breast Surgery, Hospital Israelita Albert Einstein, São Paulo, BRAZIL, ¹⁰Clinical Oncology, IDOR – Instituto D’or de Ensino e Pesquisa, Rio de Janeiro, BRAZIL.

Background: Breast cancer treatment increasingly incorporates breast-conserving approaches that integrate oncologic control with superior cosmetic outcomes. Among these, oncoplastic breast-conserving surgery (OBS), such as therapeutic mammoplasty, has gained popularity, particularly in patients with larger tumors or moderate-to-large breasts. However, robust comparative data on its oncologic safety versus standard breast-conserving surgery (BCS) remain limited, especially in low- and middle-income countries like Brazil. This multicenter cohort study aimed to compare recurrence-free survival (RFS), locoregional recurrence-free survival (LRRFS), breast cancer-specific survival (BCSS), progression-free survival (PFS), and overall survival (OS) between patients undergoing therapeutic mammoplasty and BCS.Methods: A retrospective cohort study was conducted across six Brazilian institutions (five private and one public hospital). Eligible patients were women aged 18 years or older with clinical stage 0-III breast cancer who underwent either BCS or therapeutic mammoplasty between 2016 and 2022. Data collected included demographics, tumor and treatment characteristics, and type of surgical approach. Kaplan-Meier analysis was used to estimate survival outcomes, and Cox proportional hazards models were employed to identify independent predictors of recurrence and survival. Logistic regression analysis evaluated factors associated with surgical technique selection. The study was approved by the institutional ethics committee (IDOR reference 6,907,736). Results: A total of 685 patients were included, of whom 550 (80.3%) underwent BCS and 135 (19.7%) underwent therapeutic mammoplasty. Patients who underwent therapeutic mammoplasty were significantly younger (mean age 53.3 vs. 59.5 years) and had more advanced tumor characteristics, including higher clinical T-stage (T2: 36.3% vs. 24.5%; T3: 8.1% vs. 2.5%) and greater frequency of stage IIB or higher (24.8% vs. 10.8%). Multivariate analysis showed that higher tumor stage (OR=2.71; p=0.001) and treatment in public hospitals (OR=0.41; p=0.001) were independent predictors for receiving therapeutic mammoplasty. Despite these baseline differences, survival outcomes were similar between groups. No statistically significant differences were observed for RFS (HR=0.36; p=0.091), LRRFS (HR=0.35; p=0.085), BCSS (HR=0.36; p=0.091), PFS (HR=0.52; p=0.169), or OS (HR=0.53; p=0.314). Five-year RFS rates were excellent in both groups (97.3% for therapeutic mammoplasty vs. 96.0% for BCS), as were LRRFS rates (96.6% vs. 92.2%). Positive surgical margin rates were low overall (1.5% for therapeutic mammoplasty and 4.2% for BCS), likely due to careful surgical planning, intraoperative frozen section, and larger volume resections in oncoplastic procedures. Conclusion: In this large Brazilian multicenter cohort, therapeutic mammoplasty demonstrated oncologic safety equivalent to standard breast-conserving surgery, even in patients with more advanced tumors. These results support the integration of oncoplastic techniques in breast cancer surgical care, particularly when individualized according to tumor characteristics, patient anatomy, and healthcare setting. While short- to medium-term outcomes are reassuring, prospective studies with longer follow-up are warranted to further validate the oncologic equivalence of therapeutic mammoplasty.

A. Dominique Nascimento Lima¹, A. Mattar², F. Pimentel Cavalcante³, F. Pereira Zerwes⁴, M. Antonini⁵, M. Leite Kraft⁶, A. Oliveira de Alencar³, A. de Queiroz Germano³, D. Pitanga Torres⁷, E. Goulart Carneiro⁷, C. Freitas de Lima⁷, R. Zocchio Torresan⁶, F. Palermo Brenelli⁶, M. Lichtenfels⁸, A. Frasson⁸, J. Bines⁹, E. Camargo Millen¹⁰; ¹Breast Surgery, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BRAZIL, ²Breast Surgery, Hospital da Mulher SP, São Paulo, BRAZIL, ³Breast Surgery, Hospital Geral de Fortaleza, Fortaleza, BRAZIL, ⁴Breast Surgery, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, BRAZIL, ⁵Breast Surgery, Hospital do Servidor Público Estadual, São Paulo, BRAZIL, ⁶Breast Surgery, Universidade Estadual de Campinas, Campinas, BRAZIL, ⁷Breast Surgery, Instituto Americas – Ensino, pesquisa e inovação, Rio de Janeiro, BRAZIL, ⁸Breast Surgery, Hospital Israelita Albert Einstein, São Paulo, BRAZIL, ⁹Clinical Oncology, IDOR – Instituto D’or de Pesquisa e Ensino, Rio de Janeiro, BRAZIL, ¹⁰Breast Surgery, Instituto Américas – Ensino, pesquisa e inovação, Rio de Janeiro, BRAZIL.

Background: Neoadjuvant chemotherapy (NAC) has become a cornerstone in breast cancer treatment, especially for locally advanced tumors and aggressive subtypes such as triple-negative and HER2-positive disease. NAC can reduce tumor size, increase breast-conserving surgery (BCS) eligibility, improve cosmetic outcomes, and allow early systemic control. However, concerns persist regarding whether BCS following NAC achieves oncologic outcomes comparable to those of BCS followed by adjuvant chemotherapy (AC). This study aimed to compare long-term survival outcomes in patients undergoing BCS after NAC versus AC in a real-world Brazilian cohort. Methods: We conducted a retrospective, multicenter cohort study across six Brazilian institutions (five private, one public). Women aged 18 years or older with clinical stage 0-III breast cancer who underwent BCS (either standard lumpectomy or therapeutic mammoplasty) between 2016 and 2022 were included. Patients were divided into two groups according to whether they received NAC or AC. Data on demographics, tumor characteristics, and treatments were collected from institutional registries. The outcomes assessed were locoregional recurrence-free survival (LRRFS), distant recurrence-free survival (DRFS), breast cancer-specific survival (BCSS), progression-free survival (PFS), and overall survival (OS). Survival outcomes were estimated using Kaplan-Meier methods, and Cox proportional hazards models were used to assess hazard ratios (HRs) and 95% confidence intervals (CIs). This study was approved by the IDOR Ethics Committee (reference 6,907,736). Results: A total of 268 women underwent breast-conserving surgery; 138 (51.5%) received NAC and 130 (48.5%) received AC. The mean age of the cohort was 53.1 years (SD 12.1), with patients in the NAC group being slightly younger (mean 51.1 vs. 55.2 years). Over half of the patients (56.8%) were over 50 years old, and 51.1% identified as white. Invasive ductal carcinoma was the predominant histological type (84.7%), and the majority of patients (73.8%) presented with early-stage disease (≤ stage IIA). Most underwent lumpectomy (72.4%), while 27.6% had therapeutic mammoplasty. In the NAC group, 57.2% had tumors classified as stage >IIB. After a median follow-up of 60 months, no statistically significant differences were observed in survival outcomes between the NAC and AC groups. The hazard ratio for LRRFS was 1.29 (95% CI: 0.28-5.88; p=0.816), for BCSS was 0.52 (95% CI: 0.10-2.61; p=0.473), for DRFS was 1.05 (95% CI: 0.31-3.52; p=0.955), for PFS was 1.19 (95% CI: 0.36-3.96; p=0.869), and for OS was 0.73 (95% CI: 0.18-2.91; p=0.710). Conclusion: In this multicenter Brazilian cohort, breast-conserving surgery following neoadjuvant chemotherapy was associated with survival outcomes comparable to those of surgery followed by adjuvant chemotherapy. These findings support the oncologic safety of BCS after NAC and reinforce its role as a safe and effective option in the individualized surgical management of breast cancer.

S. Jeong; General surgery, Seoul National University Bundang Hospital, Seongnam-si, KOREA, REPUBLIC OF.

Background With advances in breast cancer surgery, the proportion of breast-conserving surgery (BCS), nipple-sparing mastectomy (NSM), skin-sparing mastectomy (SSM), and breast reconstruction has increased compared to the past, when total mastectomy was the predominant approach. The introduction of NSM and SSM has enabled patients with more extensive disease to expect improvements in psychological and emotional recovery, cosmetic satisfaction, and quality of life. However, NSM and SSM are known to have a higher risk of wound complications, such as skin necrosis and infection, compared to BCS or total mastectomy. In particular, previous studies have reported that the risk of ischemic complications increases as the thickness of the skin flap decreases. Recently, due to increasing aesthetic demands and advances in medical technology, implant-based breast augmentation has become more common. Clinically, it is often observed that patients who have undergone breast augmentation with implants tend to have thinner skin flaps due to compression of the breast tissue and subcutaneous fat. Therefore, this study aims to compare the incidence of postoperative wound complications after implant-based breast reconstruction following NSM or SSM between patients with and without a history of implant-based breast augmentation. Methods In total, 817 breast cancer patients treated with nipple-sparing mastectomy (NSM) or skin-sparing mastectomy (SSM) followed by implant-based breast reconstruction between March 2019 and March 2025 at Seoul National University Bundang Hospital in South Korea were included in this study. Patients were divided into two groups: those with a history of breast implant augmentation prior to their breast cancer diagnosis (N=53) and those without such a history (N=764). To adjust for confounding variables, 1:4 propensity score matching was performed. Postoperative wound complications were classified as acute (within 4 weeks after surgery) or late (after 4 weeks), and the incidence of seroma, infection, necrosis, bleeding/hematoma, wound dehiscence, and capsular contracture was compared between the two groups using the chi-square test. Results Using 1:4 propensity score matching, 51 breast cancer patients with pre-existing implants were matched to 175 patients without implants. Patients with pre-existing implants demonstrated numerically higher rates of acute infection (13.7% vs. 5.7%, P=0.108), acute wound dehiscence (5.9% vs. 3.4%, P=0.703), late infection (5.9% vs. 4.6%, P=0.990), and late wound dehiscence (2.0% vs. 1.1%, P=1.000) compared to those without implants. Conversely, patients without implants exhibited numerically higher rates of acute seroma (5.7% vs. 0, P=0.174), acute bleeding (2.9% vs. 2.0%, P=1.000), acute necrosis (1.7% vs. 0, P=0.806), late seroma (2.9% vs. 0, P=0.497), and capsular contracture (11.4% vs. 7.8%, P=0.636). However, none of these differences were statistically significant (all P > 0.05). Conclusion While complication profiles varied between patients with and without pre-existing implants undergoing nipple- or skin-sparing mastectomy with implant-based reconstruction, these differences did not reach statistical significance. With the rising prevalence of breast augmentation, the number of breast cancer patients with pre-existing implants is expected to increase. Careful preoperative assessment and individualized surgical planning are therefore essential. Further large-scale, multi-center studies are needed to validate these findings.

R. Krishnamurthy¹, S. Joshi², R. Pathak³, A. Das Sheth², T. Wadasadawala¹, B. Kothari², D. Hoysal⁴, A. Deshpande⁴, R. Sarin³; ¹Radiation Oncology, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, INDIA, ²Surgical Oncology, Tata Memorial Hospital, Mumbai, INDIA, ³Radiation Oncology, Tata Memorial Hospital, Mumbai, INDIA, ⁴Surgical Oncology, Advanced Centre for Treatment, Research and Education in Cancer, Tata Memorial Centre, Navi Mumbai, INDIA.

BackgroundBreast conservation for multifocal (MF) and multicentric (MC) breast cancer remains contentious, particularly with evolving surgical and radiotherapy techniques. We conducted a cross-sectional survey to assess current practices, definitions, and attitudes among surgical oncologists (SOs) and radiation oncologists (ROs) regarding MF/MC breast cancer.MethodsAn online 28-item questionnaire was disseminated to consultant SOs and ROs. Responses from 82 participants across 76 institutions representing 16 Indian states and 3 union territories were analyzed descriptively. Items assessed included diagnostic definitions, indications for breast-conserving surgery (BCS), imaging, boost strategies, and multidisciplinary involvement.ResultsROs and SOs were equally represented (n=41 each), with 93% specializing in breast cancer. Most respondents were from private hospitals (74.4%), followed by government institutions (18.3%) and trust/NGO setups (7.3%).A high-volume cohort, 37% treated >50 breast cancer cases per month. MF disease was encountered ‘frequently’ or ‘very frequently’ by 40% of respondents, and MC by 34%. Most (76%) felt MF/MC incidence is rising due to advanced imaging.BCS was routinely offered for MF by 52% and conditionally by 40%; for MC, 13.6% offered it routinely, and 51% conditionally. Definitions of MC varied: 45% used quadrant-based criteria; 46% used the ≥5 cm separation rule; and 16% defined it as lesions requiring different incisions.Oncoplastic approaches were used to manage tissue deficits in 85% of MF and 76% of MC cases. Five surgeons had never offered BCS for MC, and extreme oncoplastic procedures were performed or encountered in 61% of practices. MRI was considered mandatory by 30%, while 26.5% used contrast-enhanced mammography. Biopsy of both lesions was deemed essential by 35%, with some emphasizing the importance of evaluating biological heterogeneity.Radiation strategies varied: for MF, 10% gave whole-breast irradiation (WBI) without boost, 60% gave a full boost, and 8.5% selectively boosted part of the bed. For MC, 57% boosted both tumor beds. Hypofractionated WBI (40 Gy in 15 fractions) was preferred (74%), while 11% used ultra hypofractionation selectively.IMRT/VMAT was the most commonly used boost technique (54.9%), followed by 3DCRT (38%), electrons (35.4%), and mini-tangents (20.7%). Boost decisions were typically based on tumor size, grade, nodal status, age, and receptor status, with 17.1% using all five factors.Key challenges included uncertainty in target delineation (73.2%), concerns about poor cosmesis (54.9%), and technical complexity (62.2%). Acute toxicity was also reported as a concern (42.7%). Multidisciplinary team (MDT) involvement before surgery was reported by 42.7% and postoperatively or selectively by 44%. Only 2.4% lacked access to an MDT. In 64.6% of practices, the surgical team was involved in boost planning only when the RO found it challenging; routine joint delineation was rare (7.3%). A majority (93.9%) expressed willingness to participate in a prospective study to develop consensus guidelines for boost contouring in MF/MC cases.ConclusionThis survey highlights substantial heterogeneity in surgical and radiation practices for MF/MC breast cancer across India. While breast conservation is cautiously expanding, standardized definitions and contouring guidelines are lacking. Multidisciplinary planning and tailored radiation strategies are essential. These findings underscore the urgent need for consensus protocols and prospective studies to unify practice.

P. Zhu, L. Zhu, Y. Feng, Y. Ye, S. Xu, L. Zhou, Y. Lin, Y. Wang, Y. Du, J. Lu, W. Yin; Department of Breast Surgery, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, CHINA.

Background:Skip metastasis, defined as lymphatic spread that bypasses anatomically contiguous lymph nodes, is frequently observed in breast cancer. Previous studies have reported that skip metastasis occurs in approximately 2.6% of invasive breast cancer cases¹.Lymphatic dissemination typically follows a sequential pattern, with axillary level I nodes being the most common initial site, followed by levels II, III, and occasionally other nodal basins². However, the precise patterns and underlying mechanisms of lymphatic spread remain unclear and warrant further investigation.Methods:This retrospective study included adult patients with unilateral, invasive breast cancer who underwent axillary lymph node dissection at Renji Hospital, School of Medicine, Shanghai Jiao Tong University, between October 2013, and December 2023. Patients with de novo stage IV disease were excluded.We developed a novel classification system that stratified patients based on the involvement of axillary, interpectoral (Rotter’s), and infraclavicular lymph nodes. Patients were categorized into three groups, lymph node negative (LN-), lymph node sequentially positive (LNs+) and lymph node non-sequentially positive (LNns+). LN- represents no lymph node metastasis. LNs+ means lymph node metastases following a typical anatomic sequence, from proximal to distal. While LNns+ was defined as involvement of distal nodes without proximal node involvement. Kaplan-Meier analysis and Cox proportional hazards models were used to compare disease-free survival (DFS), the primary endpoint, and recurrence-free survival (RFS) and overall survival (OS) as secondary endpoints. Results:A total of 2,838 patients diagnosed with invasive breast cancer and treated with axillary lymph node dissection were included. Based on the classification, 1,833 patients were assigned to the LN- group, 858 to the LNs+ group, and 147 to the LNns+ group, among whom 9.5% patients presented with isolated Rotter’s lymph node metastasis, 6.8% patients had isolated infraclavicular lymph node involvement and 81.0% patients with axillary nodal metastasis, infraclavicular node metastasis occurred without Rotter’s node involvement. Additionally, 4 patients exhibited combined Rotter’s and infraclavicular lymph node metastases without axillary lymph node involvement.Compared with the other two groups, the LNns+ group showed significantly different characteristics in terms of age, pathological tumor stage, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, molecular subtype, and the number of infraclavicular lymph nodes dissected (P < 0.05).In the univariate analysis, the LNns+ group consistently exhibited the poorest prognosis across DFS, RFS, and OS (P<0.001). A similar trend was observed in the multivariate Cox regression analysis (P<0.001).Conclusions: Non-sequential lymphatic metastasis may indicate more aggressive biological behavior than either the absence or sequential spread of nodal involvement. These patients may benefit from more potent treatmentsand closer surveillance during follow-up. References:1. Chung HL, Sun J, Leung JWT. Breast Cancer Skip Metastases: Frequency, Associated Tumor Characteristics, and Role of Staging Nodal Ultrasound in Detection. AJR American Journal of Roentgenology 2021; 217(4): 835-44.2. Bitencourt A, Rossi Saccarelli C, Morris EA, et al. Regional Lymph Node Involvement Among Patients With De Novo Metastatic Breast Cancer. JAMA Network Open 2020; 3(10): e2018790.

N. Bianco, C. Valenza, M. Milano, D. Trapani, S. Di Bella, A. Sciandivasci, I. Minchella, P. Veronesi, V. Galimberti, M. Intra, C. Sangalli, E. Munzone, G. Curigliano, M. Colleoni; Division of Medical Senology, European Institute of Oncology, IRCCS, Milan, ITALY.

Background: In patients with de novo metastatic breast cancer (mBC), two randomized clinical trials demonstrated that upfront breast surgery does not improve clinical outcomes. However, the role of breast surgery in patients with a locoregional oligoprogression (OPD), in the breast or locoregional lymph nodes, who previously had a response to systemic treatment is unknown. This approach may allow to maintain the same systemic treatment and prolong the time to treatment failure. Methods: We conducted a prospective-retrospective, single-center, cohort study including consecutive patients with de novo mBC, who experienced an OPD in the breast and/or locoregional lymph nodes (with other sites maintaining the best response), underwent breast surgery, and continued the same systemic treatment after surgery, according to the indication of the multidisciplinary tumor board at the European Institute of Oncology (Milan, Italy) from January 2007 to March 2025. The primary endpoint was post-surgery progression-free survival (pS-PFS), defined as the time from the first radiographic evidence of locoregional OPD to subsequent progression or death. Results: 59 patients were included: 28 (47%) had Hormone Receptor (HR)+/HER2- disease, 30 (51%) HER2+, and 1 (2%) triple-negative. When OPD occurred, the median line of treatment was 1 (IQR: 1-2), and the median pre-OPD PFS was 15.2 months (95% CI, 12.0-18.4). In the HR+/HER2- subgroup 22/28 (79%) patients were receiving an endocrine therapy-based therapy, in the HER2+ subgroup 19/30 (63%) were on trastuzumab/pertuzumab maintenance. The median time between OPD and surgery was 1.5 months (95% CI, 1.3-1.7). 12 (20%) patients underwent lumpectomy, 45 (75%) mastectomy, 5 (9%) sentinel lymph node biopsy, and 27 (46%) lymph node dissection. After a median follow-up of 54.1 months (95% CI 44.2-64.0), 38 pS-PFS events occurred in all patients, 21 in the HR+/HER2- subgroup, and 15 in the HER2+ subgroup. The median pS-PFSs were 15.0 months (95% CI, 3.7-26.3) in all patients, 9.0 months (95% CI, 4.9-13.1) in the HR+/HER2- subgroup, and 24.2 months (95% CI, 8.2-40.3) in the HER2+ subgroup.Among patients with a pre-OPD PFS ≥12 months, the median pS-PFSs was 21.4 months (95% CI, 10.2-32.6), as compared with 10.5 months (95% CI, 4.4-16.6) among those with a pre-OPD PFS <12 months (log-rank test: p=.027).Conclusions: This study suggests that selected patients with de novo mBC and locoregional OPD can benefit from breast surgery while maintaining the same systemic treatment, especially in case of HER2+ disease or a longer a pre-OPD PFS.

R. Cencelj-Arnez¹, T. Arnez², A. Perhavec¹, D. Ribnikar³, I. Ratosa⁴; ¹Division of surgery, Institute of Oncology Ljubljana, Ljubljana, SLOVENIA, ²Department of Plastic surgery, University Medical Centre Ljubljana, Ljubljana, SLOVENIA, ³Division of Medical Oncology, Institute of Oncology Ljubljana, Ljubljana, SLOVENIA, ⁴Division of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, SLOVENIA.

Background: Although radiotherapy (RT) significantly improves oncological outcomes of patients with high-risk breast cancer, it also increases complication rates and the need for corrective surgical procedures in patients undergoing breast reconstruction. The authors hypothesize that RT impacts complication rates and the need for corrective surgical procedures, especially in implant-based breast reconstruction (IBR) compared to autologous breast reconstruction (ABR). Methods: A retrospective review of consecutive patients treated at the Institute of Oncology Ljubljana and University Medical Centre Ljubljana with mastectomy and ABR or IBR in the year 2019, with or without RT, was conducted. Complication and corrective surgery rates were compared between ABR and IBR. The associations between categorical variables were investigated using Pearson’s chi-square test and multivariate analysis. A two-tailed test was used to identify significant differences with a p-value of ≤0.05. Results: In 2019, we identified 219 patients who underwent breast reconstruction; among them, 153 (69.5%) had unilateral reconstructions and 66 (30.5%) had bilateral reconstructions, resulting in a total of 285 breast reconstructions, with 106 (37.2%) being ABR and 179 (62.8%) being IBR. Most patients (87.7%) had immediate breast reconstruction. Risk-reducing surgery was done in 30.2% of reconstructions. Eighty-nine (31.2%) breast reconstructions underwent RT, of whom 46 had IBR and 43 had ABR. Twenty-eight (9.8%) reconstructed breasts received preoperative RT. We detected 22.1% of early complications and 6.3% of late complications. Patients who had preoperative RT and IBR experienced early complications more often, with 18.8% of them affected compared to only 4.8% of those who did not have preoperative RT in IBR, p=0.014. For the analysis of corrective surgery rates, we excluded breast reconstructions that had delayed-immediate ABR (3.2%) and included 276 breast reconstructions for analysis. Patients who had ABR or IBR had similar rates of corrective procedures when compared, regardless of RT (25.8% ABR no RT vs 25.6% IBR no RT; 42.5% ABR with RT vs 36.6% IBR with RT). Overall, patients who received RT had more corrective surgeries (39.5% with RT vs 25.6% no RT, p=0.502), but the difference was not statistically significant. In subgroup analysis of unilateral reconstruction, we excluded patients that later received risk-reducing contralateral mastectomy with reconstruction, and detected a difference in the symmetrization rate according to the type of reconstruction (16.1% in ABR vs 50.8% in IBR; p<0.0001). Although the difference in the symmetrization rate was detected between patients who received RT (36.8%) and those who did not (25.8%) (p=0.196), statistical significance was not observed. Conclusions: In patients with preoperative RT, IBR was associated with a higher probability of early complications. Breast reconstruction type selection does not influence the need for further corrective surgical procedures in patients receiving RT according to this analysis. Symmetrization surgery was more common after IBR. RT increases the need for symmetrization surgery in both reconstruction types.

J. El-Taraboulsi, D. Leff, P. Thiruchelvam; Department of Surgery and Cancer, Imperial College Healthcare NHS Trust, London, UNITED KINGDOM.

Introduction: Implant-based reconstructions are the most prevalent oncoplastic breast reconstruction globally. Nevertheless, the vast majority of patients undergoing nipple-sparing mastectomies (NSM) or skin-sparing mastectomies (SSM) experience total or significant sensory loss of the breast and nipple-areolar complex (NAC), as well as post-mastectomy breast pain, both key predictors of poor post-operative psychosocial and sexual wellbeing. In recent years, novel surgical techniques have been introduced to preserve sensation or neurotize the breast and NAC in NSMs and SSMs. However, the ease of implementation, reproducibility, and efficacy of such methods remain under investigation. This systematic review aims to evaluate the current literature describing surgical techniques for sensation preservation or neurotization in mastectomies with implant-based reconstructions. This includes a review of sensory outcomes from the available case-control studies, and an analysis of emerging surgical approaches, aiming to guide clinical implementation, and identify future areas of research. Method: A systematic review of open-access, English-language literature published between January 2000 and June 2025 on implant-based reconstructions offering a sensation preservation or neurotization technique was conducted across PubMed, the Cochrane Library, Google Scholar and an external search, utilizing a keyword-based advanced search. Of the 139 screened records, six prospective studies were assessed and included in the review. Results: Four surgical techniques are described across the included records, namely, intercostal nerve preservation, nerve allografting, nerve autografting, and muscle reinnervation. Despite small sample sizes, variation in follow-up duration, lack of surgical controls, and discrepancies in subjective and objective measurements of sensation across the studies, all proposed techniques improve sensory outcomes or pain reduction. Across all four proposed techniques, the data suggests that treatment groups demonstrated superior sensory outcomes. However, larger-scale studies, with prolonged follow-up periods, consistent measures of sensation and patient quality-of-life, and robust complication reporting are required to establish evidence-based guidelines for sensation preserving mastectomies with implant-based reconstruction. Conclusion: Despite limited case-control data, there is growing evidence to support that utilizing one of the following surgical techniques: intercostal nerve preservation, nerve allografting, nerve autografting and muscle reinnervation, improves breast and NAC sensation following a mastectomy with an implant-based reconstruction. This reduces the physical and psychosocial burden associated with diminished or eliminated breast sensation postoperatively. In addition, the reported complications related to these techniques are minimal, suggesting these methods are safe for clinical use.

J. Seror¹, D. Hequet¹, G. Aubry¹, M. Wilhelm¹, M. Cittanova², C. Gout-Duracher², B. Sarfati³; ¹Surgery, Institut Bourdonnais, Paris, FRANCE, ²Anesthesia, Clinique Saint Jean de Dieu, Paris, FRANCE, ³Surgery, Institut Gustave Roussy/Groupe hospitaliser Ambroise Paré Hartmann, Villejuif/Neuilly, FRANCE.

Background: Endoscopic nipple-sparing mastectomy (eNSM) is a minimally invasive technique offering improved cosmetic outcomes while preserving oncologic safety. As its international use expands, mastering the procedure presents technical and ergonomic challenges, and few studies have described the early learning curve or setup innovations [1,2].Objective: To evaluate the learning curve, perioperative outcomes, and technical refinements of eNSM in a unicentric early experience.Methods: We conducted a retrospective, descriptive study of 21 consecutive eNSM procedures between November 2024 and June 2025. The procedure was offered to patients undergoing mastectomy with immediate implant-based reconstruction. Patients with prior ipsilateral breast irradiation were excluded. We collected data on patient characteristics, indications, operative time, hospital stay, adjuvant treatments, and complications. A specific technical feature of our approach is the use of a high horizontal axillary incision, parallel to the natural axillary crease, providing optimal access and cosmetic concealment. For bilateral procedures, a single video tower positioned at the foot of the patient allowed both sides to be treated successively without reinstallation. In one case, we performed a simultaneous bilateral eNSM using two surgical teams and dual video towers, achieving a total operative time of 137 minutes for both sides.Results: A total of 21 eNSM procedures were performed: 9 unilateral and 6 bilateral. The median age was 46 years (range: 26-64). Indications included 8 multifocal tumors and 8 prophylactic mastectomies. Among the 13 invasive cancers: 9 were HR+/HER2-, 1 HR+/HER2+, and 2 triple-negative. The median tumor size was 13 mm (range: 6-30 mm), and associated DCIS was present in 4 cases (median size: 30 mm). Two patients had nodal involvement. Neoadjuvant chemotherapy was administered in 2 patients, and 1 received adjuvant chemotherapy. Two patients underwent adjuvant radiotherapy. Operative time for unilateral eNSM was a median of 105 minutes (range: 105-180), and for bilateral procedures 160 minutes (range: 137-210). A trend toward shorter operating times was observed over the series, especially with team coordination and ergonomics optimization. The fastest bilateral case (137 minutes) was achieved using a double-surgical team, double-video tower approach. One intraoperative complication occurred (bleeding requiring conversion to open surgery), during the initial phase. No postoperative complications were reported. All patients underwent immediate implant-based reconstruction (median volume: 310 cc, range: 260-525). Median hospital stay was 2 nights (range: 2-4).Conclusion: Our experience confirms the feasibility and safety of eNSM in selected patients, with a short learning curve. Technical optimizations—such as high axillary incisions and ergonomically placed video towers—facilitated bilateral procedures without repositioning. Simultaneous dual-team surgery further reduced operative time. These innovations may help standardize and streamline eNSM in high-volume centers [3].References:1. Toesca A, Peradze N, Galimberti V, et al. Robotic nipple-sparing mastectomy for the treatment of breast cancer: Feasibility and safety study. Breast. 2017;31:51-56.2. Lai HW, Chen ST, Lin SL, et al. Robotic versus conventional nipple-sparing mastectomy and immediate breast reconstruction: a case-control comparison study from Taiwan. Ann Surg Oncol. 2020;27(4):1191-1202.3. Leff DR, Vashisht R, Yongue G, et al. Endoscopic nipple-sparing mastectomy with implant-based reconstruction: a systematic review. Eur J Surg Oncol. 2021;47(1):25-32.

A. Beumer¹, M. Carlson¹, J. Maues², J. Cowden¹, S. Walker¹, A. Veach¹, J. Collins¹, K. Shanahan¹, M. E. Burkard³, K. Kalinsky⁴, A. Bardia⁵, H. Rugo⁶, M. Lustberg⁷, E. L. Papautsky⁸, A. Arcuri⁹, J. Brown⁹, M. Roberson⁹; ¹None, Patient Centered Dosing Initiative, Denver, CO, ²NA, Patient Centered Dosing Initiative, Denver, CO, ³Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, ⁴Winship Cancer Institute, Emory University, Atlanta, GA, ⁵Johnsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, ⁶Department of Medical Oncology & Therapeutics Research, City of Hope, Duarte, CA, ⁷School of Medicine, Yale, New Haven, CT, ⁸College of Applied Health Sciences, University of Illinois, Chicago, Chicago, IL, ⁹Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC.

Introduction: Many people with metastatic breast cancer (MBC) experience life-limiting side effects from MBC treatments, with most patients remaining on treatment indefinitely. While supportive medications are often used to mitigate toxicities, they may introduce additional side effects and financial cost. Individualized dosing, particularly dose reductions and frequency adjustments, is a strategy to improve tolerability with the goal of maintaining treatment efficacy. The objective of this study was to elicit MBC patient experiences with treatment toxicity, including dosing strategies and side effect management. Methods: As a follow up to a 2020 survey to characterize real-world experiences with dosing strategies (Loeser et al. 2024), the Patient-Centered Dosing Initiative (PCDI) conducted a new cross-sectional survey to elicit patient experiences and preferences related to toxicity management. The survey, distributed electronically to a convenience sample of people living with MBC in the United States, combined closed and open-ended questions. Recruitment occurred through support organization e-mail lists and newsletters, as well as closed social media groups. The survey included items associated with side effect management, knowledge and experiences of dose modifications, and supportive medication use among other topics. The survey opened April 14th 2025 and data were pulled on June 22nd for analysis, although data collection is still ongoing. Descriptive statistics, including frequency counts and percentages, were used to summarize participant responses. Associations between knowledge of dose modifications and care primarily by a breast specialist were evaluated using chi-squared tests. Results: As of the abstract submission, 340 responses were available for analysis. Surveyed patients reported all treatment drugs taken in the metastatic setting, including cytotoxic chemotherapy (35%), CDK 4/6 inhibitors (62%), HER2-targeted antibodies (24%), antibody-drug conjugates (23%), and PI3K pathway inhibitors (11%). Of the 26% who started an MBC drug at a lower dose, 69% reported that the oncologist initiated the conversation and 16% said they initiated it themselves. There was no statistically significant difference in who initiated the conversation based on whether the participant was primarily treated by a breast specialist or not (p=0.43). Overall, 57% of the respondents had their dose reduced due to side effects, whether they started at full or reduced dose, and 72% felt better on the lower dose. In addition, 27% of patients reported that their oncologist reduced the frequency of drug administration; 67% of these patients felt better with the reduced frequency. 88% of surveyed patients were aware that an MBC drug with significant side effects may have an approved dose reduction schedule. Further, 59% believed that the highest dose of a drug is not always more effective than a lower dose. Conclusions: Dose modifications are common among people with MBC, often driven by treatment toxicity and side effect management. Experiences with dose reductions did not significantly differ based on receiving care from a breast cancer specialist, suggesting broader awareness and acceptance of dose adjustments in patient and clinical communities. Notably, 83% of respondents reported starting on a lower dose, having the dose reduced, or both, indicating a need for further study into the efficacy of lower doses and for clinical trial designs in MBC that include multiple doses tested in later phases. Given that patients rarely initiated these conversations, further research is needed to understand barriers to discussing dose adjustments and to support more patient-clinician dialogue.

Y. Chen¹, Y. Wang², X. Jiang³, R. Huang¹, H. Liu³; ¹Department of Breast Surgery, Maoming People’s Hospital, Maoming, CHINA, ²Department of Breast Surgery, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, CHINA, ³Department of Plastic Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, CHINA.

Background: Restoring breast contour in Oncoplastic Breast-Conserving Surgery (OBCS) with substantial glandular excision is challenging, as traditional implants or flaps are often invasive, costly, and carry risk of complications. We assessed the feasibility of postoperative cavity remodeling technique (PCRT) that promotes autologous tissue regeneration through mechanical stabilization of the lumpectomy cavity. Methods: This retrospective case series analyzed breast cancer patients with glandular defects ≥50% who underwent PCRT. The procedure involved intraoperative suture fixation of the residual cavity, and seroma-guided endogenous remodeling, supplemented by a mini dermal-fat fascial flap for incision reinforcement. Volume and resolution of postoperative serous effusion, incision-related complication, postoperative pain using visual analog scale (VAS), aesthetic evaluation (Harris score), and patient satisfaction (BREAST-Q) were assessed. Results: Among 60 patients included, 42 (70.0%) had moderate glandular defects (50%-69%) and 18 (30.0%) had severe defects (≥70%). Postoperative fluid accumulation peaked 1 week after drain removal, with 28.3% of patients requiring aspiration. Incision-related complications occurred in 10% of patients (wound dehiscence: 5.0%; suture-site reactions: 5.0%) at 3 months after drain removal, all cases were managed with supportive care. Moderate to severe pain (VAS score of 4-6 points) was reported in 73.3% of patients 1 week postoperatively, declining to 6.7% at 3 months. Aesthetic assessment was rated as good/excellent in 81.6% of patients, and 86.7% reported high satisfaction BREAST-Q score >80 while 78.3% reported very satisfied (Likert scale) at 12 months. Conclusions: PCRT might be a minimally invasive, implant-free reconstructive approach with favorable aesthetic and patient-reported outcomes in patients with significant breast tissue loss.

K. Pfister, H. Schäffler, E. Leinert, K. Veselinovic, J. Haager, S. Lukac, S. Huesmann, B. Rack, W. Janni, V. Fink; Department of Gynecology and Obstetrics, University Hospital Ulm, Ulm, GERMANY.

Background: Mastectomies with immediate implant-based reconstruction are increasingly common, particularly among younger breast cancer (BC) patients and individuals undergoing risk-reducing surgery. Skin-sparing and nipple-sparing mastectomies are now well-established techniques; however, they are associated with specific postoperative complications. Notably, prolonged drain duration and seroma formation can hinder recovery, increasing the risk of infection, potentially requiring further intervention. Identifying risk factors for seroma formation is crucial to improving postoperative outcomes and guiding surgical planning. Methods: All nipple-sparing and skin-sparing mastectomies performed at a high-volume German breast center between January 2017 and June 2024 were retrospectively analyzed. A total of 1,298 mastectomies in 756 patients were included. Patient demographics, clinical characteristics, and perioperative data were evaluated. Seroma formation was defined as either a drain remaining in place beyond postoperative day 7 or the need for seroma aspiration following drain removal. Results: Among the 1,298 mastectomies, 389 (30.0%) met the criteria for seroma formation. Oncologic indications (e.g., DCIS or invasive BC) were significantly associated with higher rates of seroma formation compared to risk-reducing procedures. Older age, higher BMI, and the presence of medically treated hypertension were also significantly associated with increased seroma risk. No significant associations were found with neoadjuvant chemotherapy, diabetes, smoking status, or anticoagulant use. The type of mastectomy (skin-sparing vs. nipple-sparing), the use of mesh for stabilization, and the plane of reconstruction (prepectoral vs. retropectoral) did not affect the incidence of seroma. However, higher implant weight and greater drain output within the first three postoperative days were strongly correlated with seroma formation (p < 0.001). Patients in the seroma group experienced significantly more postoperative infections (8.0% vs. 2.6%, p < 0.001), although rates of revision surgery and delayed wound healing were not significantly different. Conclusion: This large retrospective cohort study identifies key clinical and surgical factors associated with seroma formation following mastectomy with immediate reconstruction. These findings underscore the importance of individualized risk assessment and may inform patient counseling and surgical decision-making to reduce postoperative morbidity.

J. Lucocq¹, H. Baig¹, K. Elder¹, G. Urquhart², R. Sharma³, L. Romics⁴, B. Elsberger⁵; ¹Edinburgh Breast Unit, Western General Hospital, Edinburgh, UNITED KINGDOM, ²Oncology Department, Aberdeen Royal Infirmary, Edinburgh, UNITED KINGDOM, ³Oncology Department, Aberdeen Royal Infirmary, Aberdeen, UNITED KINGDOM, ⁴Department of Academic Surgery, University of Glasgow and National Health Service Greater Glasgow and Clyde, Glasgow, UNITED KINGDOM, ⁵Breast Unit, Aberdeen Royal Infirmary, Aberdeen, UNITED KINGDOM.

Introduction: Recent and historical trials have suggested that the omission of axillary surgery is oncologically safe in node-negative early breast cancer. This meta-analysis investigates the feasibility of the omission of axillary surgery (SLNB or ALND) in terms of oncological outcomes and adjuvant treatment decisions. Method: A systematic search of Medline, Embase and Cochrane Central was conducted. Random-effect meta-analysis was conducted to compare recurrence and survival outcomes between omission of axillary surgery and SLNB or ALND. Differences in real-world adjuvant treatment decisions and patient reported outcomes were investigated. Results: Ten studies (omission, n=3716; SLNB/ALND, n=4604/785) investigated oncological outcomes (pooled rates, T1 – 88%; Grade 1-2, 80%; ER-positive 91.2%; HER2-positive 4.4%; ductal carcinoma 74%). In the omitted group, the pooled rates of local, axillary and distant recurrence (follow-up, 8 years 9 months) were 3.6% (95%CI,2.0-6.5%), 2.5% (95%CI,1.3-4.8%; 5year, 1.0%) and 3.6% (95%CI,2.0-6.5%; 5year, 2.7%), respectively. In comparison to SLNB/ALND, there were no differences in local recurrence (OR 0.91; 95%CI,0.56-1.50), distant metastasis (OR 0.91; 95%CI,0.56-1.50), BCM (OR 1.00; 95%,CI 0.63-1.60), OS (HR 0.88; 95%CI,0.65-1.19) or DFS (HR 0.91; 95%CI,0.76-1.11). Axillary recurrence was higher in the omission group compared to SLNB/ALND (OR 4.42, 95%CI,1.5-12.8) but not in SLNB alone (OR 2.85 95%CI 0.1-133.8). Omission of axillary surgery was associated with lower rates of adjuvant chemotherapy, radiotherapy and hormonal treatment but quality of evidence was poor. Conclusion: Omission of axillary surgery is safe in node-negative early breast cancer. Prospective data is required to investigate the impact of omission on adjuvant treatment decision.

Y. Zheng, Y. Chen, E. Xia, O. Wang; Department of Breast Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, CHINA.

Objectives: Over the last decade, axillary management strategies for patients with breast cancer have experienced several paradigm shifts toward surgical de-escalation, especially in exceptional responders who have achieved a complete response after neoadjuvant systemic therapy (NST). Current trends in axillary surgery for breast cancer patients who achieved clinical complete response (cCR) to neoadjuvant systemic therapy (NST) are unknown.Methods: In this retrospective cohort study, female patients diagnosed with breast cancer who achieved cCR after NST were selected from the Surveillance, Epidemiology, and End Results database (2010-2021). The proportions of patients undergoing each axillary treatment approach were summarized by year of diagnosis to assess the trend of axillary management strategy. The Cox proportional hazard models with the inverse probability of weighting (IPW) were used to evaluate the effects of axillary surgery on overall survival (OS) and disease-specific survival (DSS). A multivariate logistic regression model was used to explore factors associated with axillary pathological (p)CR.Results: In total, 15,111 patients were included. The nodal positivity rate after NST in cCR patients with initially clinical node-negative breast cancer was only 0.56%, while the nodal negativity rate after NST in cCR patients with initially clinical node-positive breast cancer was 49.57%. Between 2010 and 2021, axillary lymph node dissection (ALND) rates decreased from 55.27% to 29.07% while sentinel lymph node biopsy (SLNB) rates increased from 41.04% to 64.84%. From 2010 to 2021, the percentage of patients with initially node-negative disease receiving ALND after NST decreased from 32.92% to 13.03%, whereas those receiving SLNB increased from 66.24% to 80.82%.Patients who received ALND had worse OS than those who received SLNB (hazard ratio [HR] = 1.662, 95% confidence interval [CI], 1.339-2.063, P < .001). After applying the inverse probability weighting (IPW), patients in the ALND group still had a worse OS than those in the SLNB group (HR = 1.491, 95%CI, 1.164-1.911, P < .001). Meanwhile, patients who received ALND were associated with worse DSS than those who received SLNB (HR = 1.909, 95%CI, 1.485-2.453, P < .001). Despite the application of IPW, the DSS of patients in the ALND group remained inferior to that of the SLNB group (HR = 1.654, 95%CI, 1.243-2.202, P < .001).The logistic regression analysis revealed that initial cN0 was a strong predictor of axillary pCR. Patients who were initially diagnosed with N1 (OR, 0.024; 95% CI, 0.022-0.027), N2 (OR, 0.036; 95% CI, 0.029-0.043), and N3 (OR, 0.028; 95% CI, 0.023-0.034) stages had a decreased odds of achieving axillary pCR.Conclusions: In summary, the results of this study indicated that ALND was administered to up to 13% of patients with originally node-negative breast cancer who achieved cCR following NST. Compared to SLNB, ALND may reduce the survival of patients who obtained nodal pCR, indicating potential overtreatment. In this subgroup of patients, we recommend carrying out SLNB first to determine the node status before the decision to undergo ALND.

J. Schneider¹, Y. An², H. Choi³, Y. Suh⁴; ¹Medicine, Texas Tech University Health Sciences Center, Lubbock, TX, ²Diagnostic radiology, The Catholic University of Korea St. Vincent’s Hospital, Suwon, KOREA, REPUBLIC OF, ³Pathology, The Catholic University of Korea St. Vincent’s Hospital, Suwon, KOREA, REPUBLIC OF, ⁴Surgery, The Catholic University of Korea St. Vincent’s Hospital, Suwon, KOREA, REPUBLIC OF.

Objective: In a previous clinical study, we demonstrated that it is feasible to perform volume displacement using diced acellular dermal matrix (dADM) immediately after breast-conserving surgery (BCS) in patients with operable breast cancer. However, we realized that unexpected non-infectious erythema could present as a complication, which led us to develop a new approach to address this issue. Summary Background Data: Previous study proved dADM was effective to fill the defect in the breast after BCS, however, some patients showed intramammary fat necrosis during adjuvant chemotherapy or postoperatively following non-infectious erythema on the skin over the cavity filled with dADM. We take into consideration of embryological characteristics of breast to minimize this complication by changing approach route through retromammary plane, while maintaining its proven advantage. Methods: After institutional review board approval, we prospectively recruited 530 breast cancer patients requiring BCS from August 2019 to June 2022. Incision was made along the periphery of breast mound including axilla or inframammary fold, where the minimum distance was expected from the incision to the index tumor. After breast cancer removal, cavity was filled with dADM. After surgery, all patients received adjuvant local irradiation treatment, systemic chemotherapy, targeted agent or endocrine treatment according to the recommendations of international treatment guidelines according to the type of molecular subtype. All enrolled patients were followed up at 2 months after completion of both chemotherapy and external radiation treatment and up to 3 years from the date of surgery, including systemic evaluation to assess the occurrence of any complications, including non-infectious erythema, and oncologic outcome related to locoregional recurrence or systemic metastasis. Results: Of 530 patients enrolled, only 5 patients showed intramammary fat necrosis. Locoregional recurrence and systemic metastasis rates were also not statistically different from previous results not included in this study.Conclusions: Retromammary BCS and volume displacement with dADM for operable breast cancer is effective for reducing fat necrosis postoperatively, even after repetitive episodes of neutropenia during systemic chemotherapy, and is easy to preserve preoperative breast mound volume and shape. Although further clinical studies are needed in a larger number of patients, we believe that this surgical method could be another oncoplastic BCS that can overcome the limitations of conventional BCS.

L. Weydandt, K. Hein, S. Briest, I. Nel, B. Aktas; Department of Gynecology, University hospital Leipzig, Leipzig, GERMANY.

Purpose: Seroma is the most common postoperative complication following mastectomy, often prolonging hospital stays and increasing the need for additional treatment. Despite its high prevalence, the etiology and predictive factors remain unclear. Therefore, identifying reliable predictors and potential causes remains a critical focus in research. This study aimed to identify potential risk factors associated with seroma formation following mastectomy. Methods: We conducted a retrospective analysis of 244 patients who underwent mastectomy at the University Hospital Leipzig between 2019 and 2023. Data was extracted from the patient’s medical record and from pathology reports. The analysis focused on selected factors including epidemiological patient’s characteristics, preoperative treatments (e.g. neoadjuvant chemotherapy), tumor status (e.g. TNM classification), perioperative (e.g. surgery duration) and postoperative variables (e.g. drainage duration). Seroma formation was assessed based on the flow rate from wound drains placed in the breast and axilla and follow-up visits. Statistical methods included Spearman correlation, t-tests, ANOVA, and multivariate regression to identify risk factors associated with seroma development. Results: The median patient age was 51 years (range 18-88). A total number of 301 mastectomies procedures were performed on 244 patients. Of these mastectomies, 215 (71.4%) were conducted due to breast cancer, 24 (8.0%) due to ductal carcinoma in situ and 62 (20.6%) as a prophylactic intervention. In 145 (48.2%) cases a mastectomy with immediate implant-reconstruction was performed, in 156 (51.8%) a mastectomy without reconstruction was performed. In 123 (40.9%) cases the mastectomy was combined with a sentinel node biopsy procedure, in 89 cases (29.6%) with an axillary dissection and in 89 cases (29.6%) no axillary treatment was performed. The median amount of total seroma was 585 ml (range 35-3625 ml). Epidemiological factors found to be significant were patients’ age (r=0.19; p<0.001), BMI (r=0.24; p<0.0001), hypertension (T=-3.52; p<0.001), and diabetes (T=-2.18; p<0.05). Among preoperative treatments found to be significant was previous breast surgery (T=2.25; p<0.05). Furthermore, significant factors regarding tumor status were, tumor size (r=0.33; p<0.001) and histology (F=3.71; p<0.001), removed specimen weight (r=0.31; p<0.0001), number of metastatic lymph nodes (r=0.42; p<0.0001), lymphovascular invasion (r=0.27; p<0.0001) and nodal status (r=0.41; p<0.0001). Perioperative variables found to be significant were the number of removed lymph nodes regardless of metastastic state (r=0.55; p<0.0001), duration of surgery (r=0.13; p<0.05) and inserted implant size (r=0.27; p<0.001). Significant postoperative parameters were C-reactive protein (CRP) -value on the first postoperative day (r=0.24; p<0.0001), amount of seroma in the first 24 hours (r=0.47; p<0.0001) and the duration of drainage (r=0.68; p<0.0001). Conclusion: These results suggest that both patient-related and treatment-related factors significantly influence postoperative development of seroma following mastectomy. Higher seroma volumes were associated with older age, higher BMI, comorbidities (such as hypertension and diabetes) and lymph node removal. Recognizing these risk factors may help guide postoperative management to reduce complications.

N. Polidorio¹, R. Frederice¹, G. Azevedo Gabriele Carlos¹, T. Dassie¹, R. Sousa-Barroso²; ¹Breast Surgery, Rede Americas Oncology, São Paulo, BRAZIL, ²Breast Medical Oncology, Rede Americas Oncology, Brasília, BRAZIL.

Background: Axillary lymph node dissection (ALND) remains the standard of care for patients with breast cancer with residual nodal disease (ypN+) after neoadjuvant chemotherapy (NAC). While the results of randomized controlled trials on the safety of omitting ALND are still awaited, retrospective studies suggest that de-escalation is already incorporated into clinical practice. This systematic review and meta-analysis aimed to evaluate oncological outcomes of sentinel lymph node biopsy (SLNB) alone versus ALND in patients with residual nodal disease after NAC. Methods: A systematic search of PubMed, Embase, and the Cochrane Library was performed. Eligible studies included randomized controlled trials and observational cohort studies of patients with clinically node-positive breast cancer who received NAC and were found to have ypN+ disease at surgery. Studies reporting outcomes of axillary recurrence, distant recurrence-free survival (DRFS), and/or overall survival (OS) were included. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing SLNB to ALND were extracted or estimated from Kaplan-Meier curves using validated methods. A random-effects meta-analysis was conducted. Results: Nine retrospective studies encompassing a total of 13,160 patients were included in the analysis. Of these, 3,831 patients underwent SLNB alone, while 9,329 underwent ALND. Axillary recurrence outcomes were reported in six studies. The pooled axillary recurrence rate was 5.91% (95% CI: 3.47%-9.92%) in the SLNB group and 5.24% (95% CI: 3.66%-7.44%) in the ALND group. SLNB was associated with a statistically significant reduction in axillary recurrence compared to ALND (HR = 0.94, 95% CI: 0.90-0.99), although the difference may not be clinically meaningful. Five studies reported DRFS with no significant difference between SLNB and ALND (HR = 0.99, 95% CI: 0.83-1.18), though substantial heterogeneity was present (I² = 69.7%), suggesting variability that may affect outcomes. Eight studies reported OS outcomes and no significant difference in OS between the two groups (HR = 1.08, 95% CI: 0.94-1.24, p = 0.26). Notably, all these findings may reflect selection bias, as patients selected for SLNB alone may have been more likely to have favorable baseline characteristics. Conclusion: This meta-analysis of retrospective studies suggests that omission of ALND in ypN+ patients does not compromise axillary control and may be associated with comparable regional and distant control with similar survival. However, due to the inherent limitations of retrospective data—including potential selection bias and unmeasured confounding—these findings should be interpreted with caution. Prospective randomized trials are necessary to confirm the safety of omitting ALND and to identify which patients may be appropriate candidates for axillary surgery de-escalation.

L. d. Paz¹, J. V. Biazús²; ¹Department of Breast Surgery, Aristides Maltez Hospital; Oncoclínicas&Co –Medica Scientia Innovation Research (MEDSIR), Salvador, BRAZIL, ²Postgraduate Program in Health Sciences: Obstetrics and Gynecology, Federal University of Rio Grande do Sul, Porto Alegre, BRAZIL.

Background Breast reconstruction (BR) is an essential component of breast cancer treatment, contributes to quality of life. Implant-based techniques are the most commonly used for immediate reconstruction following mastectomy. Subpectoral implant placement offers benefits such as reduced implant palpability and decreased risk of rippling. Complete implant coverage also provides greater protection and prevents lateral migration of the implant. Traditionally, the inferolateral coverage in total submuscular reconstruction is achieved using the serratus anterior muscle flap (SMF). However, this approach is associated with potential donor site morbidity. Alternatives include synthetic meshes, acellular dermal matrices (ADMs), dermal flaps, and the serratus anterior fascia flap (SFF). The high cost limits the widespread use of ADMs. The SFF has emerged as a promising autologous alternative. Despite its potential, limited data exist on the use of SFF in immediate BR. This study aims to compare clinical, surgical and oncologic outcomes, including time to first adjuvant therapy between patients undergoing subpectoral BR with either the SFF or the SMF for inferolateral implant coverage. Methods A retrospective review was conducted of 209 medical records of women aged 18 years or older diagnosed with stage I-III invasive breast carcinoma. All patients underwent mastectomy followed by immediate subpectoral implant-based BR and received subsequent adjuvant chemotherapy or radiotherapy at Aristides Maltez Hospital, Salvador-BA, Brazil from January 2018 to December 2022. Patients were grouped based on the type of inferolateral implant coverage used: SFF (n=53; 25.4%) or SMF (n=126; 60.3%). Thirty patients with unrecorded flap details were excluded from analysis. Clinical, oncologic, and demographic data were extracted from medical records. The time from surgery to the initiation of adjuvant therapy (defined as either first chemotherapy cycle or first radiotherapy session) was calculated. Results The median age was 44 years (IQR 38-50), with a predominantly black women population (90.5%). The SFF group received significantly larger implants [375 mL (IQR 305-475) vs. 337.5 mL (IQR 300-390); p=0.01] and had a higher rate of direct-to-implant reconstruction (98.1% vs. 61.2%; p<0.01). No significant differences were observed between groups regarding age, menopausal status, clinical stage. The median time from surgery to initiation of adjuvant therapy was 11 weeks in both groups. Conclusions The SFF is a viable and cost-effective alternative to SMF or ADMs in immediate BR. It supports the use of larger implants, does not delay the initiation of adjuvant therapy. These findings highlight the broader applicability of SFF in reconstructive planning, particularly in resource-constrained settings.

E. Kohilakis¹, S. Chow², N. Habboosh², M. Bajwa², M. McEvoy², S. Feldman²; ¹Internal Medicine, Montefiore Medical Center, Bronx, NY, ²Surgery, Montefiore Medical Center, Bronx, NY.

Background: Breast cancer-related lymphedema (BCRL) remains a persistent and impactful morbidity associated with axillary surgery. Even with sentinel lymph node biopsy (SLNB), the reported incidence of BCRL is 5-7%. As surgical oncology shifts toward minimizing treatment-related morbidity—particularly in patients with clinically node-negative, early-stage breast cancer—techniques that reduce the risk of BCRL are increasingly valuable. Large trials such as SOUND and INSEMA support de-escalation of axillary surgery, demonstrating that SLNB may be safely omitted in select low-risk patients. These findings reinforce efforts to refine surgical techniques for those who still require axillary staging. Technique: We propose a novel, broadly applicable surgical approach: lymphatic-sparing sentinel lymph node biopsy (LSSNBX). This technique preserves and reapproximates the afferent and efferent lymphatic channels after sentinel node excision to facilitate lymphangiogenesis and reduce postoperative lymphedema risk. Unlike axillary reverse mapping (ARM)-dependent approaches, LSSNBX avoids additional mapping procedures, making it more feasible in varied practice settings. The procedure begins with dual-agent mapping (Technetium-99m, indocyanine green [ICG], or blue dye). After identification of the sentinel lymph node, an axillary crease incision is used to access the node. During excision, the afferent and efferent lymphatic bundles are carefully preserved and prevented from retracting. These lymphatic channels are then reapproximated using an absorbable suture, promoting potential reconnection and continuity of lymphatic flow. Importantly, this method simplifies prior ARM-based strategies by performing lymphatic preservation routinely, regardless of ARM findings. Results: A retrospective review at our institution included 103 patients: 52 underwent LSSNBX and 51 underwent standard SLNB without lymphatic preservation. Patient demographics indicated the LSSNBX group was older and had a lower mean BMI. At three-month follow-up using bioimpedance spectroscopy (SOZO®), no cases of BCRL were identified in either group. Notably, the LSSNBX technique added minimal operative time and required no specialized equipment, supporting its feasibility and cost-effectiveness. Conclusion: LSSNBX is a safe, simple, and scalable modification of standard SLNB that aligns with the current movement toward minimally invasive, morbidity-reducing surgical oncology. By preserving and reapproximating lymphatic channels intraoperatively, this technique may reduce the incidence of BCRL and improve long-term patient quality of life. As axillary surgery continues to evolve, the LSSNBX technique represents a promising step in optimizing outcomes. Further studies with larger cohorts and extended follow-up are warranted to validate these preliminary findings.

S. Lee¹, J. Ahn¹, S. Lim², H. Alanazi¹, H. Park¹; ¹Surgery, Yonsei University College of Medicine, Seoul, KOREA, REPUBLIC OF, ²Surgery, Inha University Colleage of Medicine, Incheon, KOREA, REPUBLIC OF.

Background : Robotic-assisted breast surgery has emerged as a minimally invasive option to achieve oncologic safety and favorable cosmetic outcomes. While robotic-assisted nipple-sparing mastectomy has been studied, data on robotic-assisted partial mastectomy (RAPM) remain limited. This pilot study aimed to compare surgical and patient-reported outcomes between RAPM and conventional partial mastectomy (CPM) in patients with early-stage breast cancer. Methods : This was a non-randomized, prospective comparative pilot study conducted at Severance Hospital between March and July 2024. Ten patients were enrolled, with five undergoing RAPM and five undergoing CPM. Clinicopathologic characteristics, operative outcomes, complication rates, costs, and patient-reported outcomes were analyzed. Fisher’s exact test and the Mann-Whitney test were used to compare categorical and continuous variables, respectively. Results : There were no significant differences in age (median 54.0 vs 48.0 years, p = 0.095), BMI (24.9 vs 21.7, p = 0.095), menopausal status, hormone receptor status, HER2 expression, Ki-67 index, histologic grade, or TNM stage between groups (all p>0.05). The incision size was significantly smaller in the RAPM group (2.74cm vs. 5.20cm, p=0.008). Operative time, blood loss, drain output, and postoperative complications were similar. One patient in the RAPM group experienced a hematoma and wound dehiscence. Surgical cost was approximately 5,000 USD higher in the RAPM group, but the difference was not statistically significant (p=0.140). Patient satisfaction and health-related quality of life (HRQoL) were assessed using the BREAST-Q and EQ5D_5L. Postoperative satisfaction improved in both groups. BREAST-Q scores were slightly higher in the CPM group (100.2 vs. 95.2, p = 0.690), while EQ5D_5L index scores were slightly higher in the RAPM group (0.8498 vs. 0.8276, p = 1.000). No statistically significant differences were observed. Conclusion : RAPM was shown to be a feasible and safe alternative to CPM for early-stage breast cancer patients. While both techniques yielded comparable clinical and patient-reported outcomes, RAPM demonstrated a significant cosmetic advantage due to a smaller incision size. These findings support further evaluation of RAPM in larger, long-term studies.

R. Nishimura¹, Y. Ueda², K. Kiyohara², M. Funagayama², N. Ikeda², A. Kato², H. Tokiniwa², R. Higashi³, M. Nakahara³, H. Ifuku³, T. Hayashi⁴, Y. Sagara⁵, Y. Sagara⁵, S. Ohno⁵; ¹Department of Breast Surgery, Fukuda Hospital, Kumamoto City, JAPAN, ²Department of Breast Surgery, Sagara Hospital Miyazaki, Miyazaki City, JAPAN, ³Department of Radiology, Sagara Hospital Miyazaki, Miyazaki City, JAPAN, ⁴Department of Pathology, Sagara Hospital Miyazaki, Miyazaki City, JAPAN, ⁵Department of Breast and Thyroid Surgical Oncology, Sagara Hospital, Kagoshima City, JAPAN.

Background: Sentinel Lymph Node Biopsy (SLNB) in breast cancer is a standard procedure used to determine whether breast cancer has spread to the axillary lymph nodes. It has replaced full axillary lymph node dissection (ALND) in early-stage clinically node-negative (cN0) breast cancer patients. However, SLNB is associated with some rare complications such as pain, seroma and lymphedema. Omission of SLNB in breast cancer is an evolving area in clinical practice and may be a safe and reasonable option. To identify cases in which SLNB was negative, we conducted a retrospective study using early breast cancer data from our hospital registry. Methods: A total of 2,589 breast cancer patients underwent SLNB between June 2016 and April 2025. Of these, 1,956 cases of cN0 invasive breast cancer who did not undergo preoperative chemotherapy were included in this retrospective study. Pathological diagnosis using frozen section or one-step nucleic acid amplification (OSNA) method was used for the diagnosis of SLNs. The number of SLNs examined ranged from 1 to 7, with a mean of 1.8 nodes. The disease-free survival (DFS) was calculated using the Kaplan-Meier method and analyzed using the log-rank procedure. The multivariate analysis of factors for negative SLN was performed using logistic regression analysis. Results:1. Metastasis to the SLNs was observed in 379 cases (19.4%) including micro-metastasis. The median number of metastatic SLN was 1.0. SLN metastasis was observed in 139 (14.5%) cases with breast conserving surgery (Bp) and 240 (24.1%) cases with total mastectomy (Bt). Of cases with positive SLN, 378 cases (87.9%) received ALND. 2. Cases with invasive ductal carcinoma (IDC) had a 19.9% positive SLN rate and cases with invasive lobular carcinoma (ILC) and invasive micropapillary carcinoma (IMPC) had higher positive rates than IDC. 3. SLN metastasis was not associated with ER, PgR and HER2 status. However, significant differences were observed in age, tumor size, Ki-67 index value and histological grade. The incidence of SLN metastasis was significantly lower in patients aged 50 years or older (postmenopausal), a tumor size of 2 cm or less, a Ki-67 index value 50 years of age, a tumor size of ≤ 2 cm and a HG of 1 was favorable regardless of the presence or absence of SLN metastasis (99.5% for negative SLN and 100% for positive SLN). Conclusion: Metastasis to SLN was found in 19.4% of cN0 breast cancer cases. Factors related to negative SLN were age (50 years or older), tumor size (2cm or less), and HG (1), and the positive SLN rate was significantly higher in cases with the Luminal B subtype. The prognosis for cases with the above factors was good, and recurrences were rarely observed. In the future, whether SLNB is required will depend on the above-mentioned patient characteristics.

Y. Ishizaka, T. Sakai, M. Kasahara, M. Kai, A. Kanazawa, E. Taniguchi, Y. Ito, Y. Kimura, U. Nakadaira, Y. Inoue, T. Maeda, N. Yamashita, A. Kataoka, N. Uehiro, T. Ueno; Breast Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, JAPAN.

Background Metastasis to the internal mammary lymph nodes (IMLN) plays a critical role in the regional staging and prognosis of breast cancer. Although IMLN involvement often occurs alongside axillary lymph node (AXLN) metastasis, isolated IMLN metastasis without axillary involvement (cN2b) is rare, and the optimal surgical approach for these patients remains uncertain. While axillary lymph node dissection (ALND) is generally recommended for node-positive disease, its necessity in cases of cN2b is debatable. This study aims to clarify the prognostic significance of AXLN status and to assess whether ALND can be safely omitted in breast cancer patients presenting with isolated IMLN metastasis. Methods We retrospectively analyzed patients with IMLN metastases confirmed preoperatively by cytology, who underwent surgery at our institution between 2007 and 2021. Inclusion required cytological confirmation of IMLN metastasis. Exclusion criteria included clinical T4 tumors, supraclavicular or distant metastases, and bilateral breast cancer. Patients were stratified into two groups: cN2b (isolated IMLN metastasis, n=21) and cN3b (IMLN with AXLN metastasis, n=104). Clinicopathological characteristics and 5-year disease-free survival (DFS) were compared between groups. In the cN2b cohort, oncologic outcomes were further evaluated according to the type of axillary surgery performed: sentinel lymph node biopsy (SLNB) alone versus ALND. Results Of 15,231 surgically treated breast cancer patients, 230 had IMLN metastasis. After exclusions, 125 (0.8%) were included: 21 (0.1%) with cN2b and 104 (0.7%) with cN3b. The median follow-up was 59 months. The cN2b group demonstrated a significantly higher frequency of medial tumor location (52% vs. 30%, p=0.046) and tended to present with smaller tumor size compared to the cN3b group (p=0.039). Histologically, invasive ductal carcinoma was the predominant subtype in both groups. Hormone receptor-positive tumors accounted for the majority of cases in both cN2b and cN3b groups (62% and 60%, respectively, p=0.85). HER2-positive tumors were seen in 19% of cN2b and 26% of cN3b cases (p=0.50).The 5-year DFS was significantly better in cN2b patients compared to cN3b (94.7% vs. 64.0%, p=0.0049), indicating favorable prognosis in the absence of axillary involvement. Among cN2b patients, 10 underwent SLNB alone and 10 underwent ALND. The remaining patient did not undergo any axillary surgery due to personal preference. DFS rates did not significantly differ between these subgroups (88.9% for SLNB vs. 100% for ALND, p=0.32). In the cN2b group, 20 patients (95.2%), and in the cN3b group, 101 patients (97.1%) received postoperative radiotherapy, with irradiation fields including the regional lymph node areas in all cases. One SLNB-only patient developed distant bone metastasis, but no regional axillary recurrence occurred in any group. Two ALND patients had previously undetected axillary metastases though it is unclear whether these findings had any effect on DFS. Conclusions This study suggests that breast cancer patients with isolated IMLN metastasis and no axillary involvement (cN2b) have significantly better outcomes than those with combined IMLN and AXLN metastasis (cN3b). Furthermore, omission of ALND in cN2b cases may be feasible and did not appear to compromise disease control, with no locoregional failures observed in the SLNB-only group. These findings support the potential safety and efficacy of a less invasive axillary management strategy—SLNB alone—for appropriately selected cN2b patients. Considering the rarity of this clinical subset, larger prospective studies are warranted to further validate these findings and refine treatment guidelines for isolated IMLN metastasis.

G. Falco¹, Y. L. Eaglehouse², S. Darmon², M. Nealeigh², R. W. Krell², C. D. Shriver², K. Zhu²; ¹Surgery, San Antonio Military Medical Center, Fort Sam Houston, TX, ²Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD.

Background: Breast cancer is the most commonly diagnosed cancer among women—either active duty, retirees, or dependents—in the U.S. Military Health System (MHS). Surgical treatment is an essential component of treatment for patients without metastatic disease. Differences in insurance coverage and access to care by patient age in the general U.S. population may affect breast cancer diagnosis and surgery. The impact of age on surgical outcomes in breast cancer under conditions of universal healthcare access remains unclear. This study compared postoperative outcomes following breast cancer surgery according to patient age at diagnosis in the U.S. MHS, which provides universal access to care to all its beneficiaries with no or minimal out-of-pocket cost. Methods: We identified women aged 18 and older with stage I-III breast cancer between 2001 and 2014 undergoing partial or total mastectomy without reconstruction in the MilCanEpi database. Multivariable Poisson regression estimated the adjusted risk ratios (ARRs) with 95% confidence intervals (CIs) in association with age at diagnosis (18-39, 40-49, 50-64, and >65) for 30-day general and breast complications (surgical site infection, seroma, hematoma, or lymphedema), reoperation, and hospital readmission while controlling for potential confounders. Results: The study included 7,835 women who were 18-39 (9.2%), 40-49 (23.6%), 50-64 (42.7%), and >65 (24.5%). Women 18-39 were more likely to present with stage III tumors (20.2%) and high-grade tumors (51.5%) than other age groups. While older women (>65) had higher unadjusted rates of any complication (RR=1.34; 95% CI=1.12-1.60) or general complication (RR=1.77; 95% CI=1.25-2.50) relative to women diagnosed at age 50-64, these differences were not statistically significant after multivariable adjustment for demographic, tumor, and treatment variables and time to surgery. The overall risk of any breast complication did not differ significantly by age. However, women aged 40-49 had a statistically increased adjusted risk of seroma (ARR=1.50; 95% CI=1.03-2.18) compared to women age 50-64. No significant age-related differences were observed for reoperation or hospital readmission after adjustment. Conclusion: In the universal-access Military Health System, the risk of 30-day postoperative complications and hospital readmissions varied by age among women undergoing surgery without reconstruction for non-metastatic breast cancer. However, these differences were attenuated after adjustment for clinical and demographic factors, suggesting that age may play a limited role in short-term surgical outcomes for breast cancer. Surgical decision-making should continue to prioritize tumor characteristics, comorbidity burden, and other clinical factors rather than age alone when assessing perioperative risk. Disclaimer: The contents of this abstract are the sole responsibility of the authors and do not necessarily reflect the views, assertions, opinions, or policies of the Uniformed Services University of the Health Sciences, the Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., the Department of Defense, or the Departments of the Army, Navy, or Air Force. Mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. government.

M. A. Thill¹, E. Klein², T. Lantzsch³, D. Rezek⁴, L. Bauer⁵, K. Kelling¹; ¹Klinik für Gynäkologie und Gynäkologische Onkologie, Agaplesion Markus Krankenhaus, Frankfurt, GERMANY, ²Klinik für Gynäkologie und Geburtshilfe, Technische Universität München, München, GERMANY, ³Klinik für Frauenheilkunde und Geburtshilfe, Krankenhaus St. Elisabeth und ST. Barbara Halle (Saale) GmbH, Halle (Saale), GERMANY, ⁴Senologie und Ästhetische Chirurgie, Evangelisches Krankenhaus Wesel GmbH, Wesel, GERMANY, ⁵Klinik für Gynäkologie und Gynäkologische Onkologie, GNR-Klinik Weinheim, Weinheim, GERMANY.

Background: Implant reconstruction after breast removal is a common method of restoring the appearance of the breast. For many years, the subpectoral implant position was considered the gold standard. However, due to the advancement of technology, the current standard is the prepectoral implant position. To support this technique, resorbable or non-absorbable meshes or acellular dermal matrices can be used in the reconstruction to stabilize the implant, fix it and preform a capsule. Meta-analyses have shown that neither the pre- nor the subpectoral position is an advantage for the patient in terms of complication rate. With regard to the use of meshes or matrices, there is still no head-to-head comparison between a mesh, an ADM or nothing. The aim of this study is to determine the patient-reported and cosmetic outcome, as well as the complications associated with the use of the fully absorbable TIGR mesh in the prepectoral implant reconstruction of the breast.Trial design: The PRO-TIGR-Matrix-PREPECTORAL study is a national, prospective, multicentre post market surveillance study on „Patient Reported Outcome“ of implant based primary or secondary reconstructive breast surgery after mastectomie using the complete resorbable synthetic Matrix (TIGR-Matrix, Novusscientific Sweden). The observation period is 3 years with a focus on patient reported satisfaction (as measured by BreastQ^TM), cosmetic outcome and complication rate. The study period will be 54 months, per patient: 36 months plus optional further follow-up surveys as part of the usual follow-up until the end of the study. The recruitment phase will be 18 months, the follow-up phase 36 months. 135 patients will be recruited.Primary endpoints: The primary endpoint of this clinical investigation is to assess quality of life after 12 months determined by the questionnaire BreastQ^TM. The study is considered successful, if and only if non-inferiority can be established for all four domains. Secondary endpoints: The secondary endpoints are patient reported outcome/quality of life measured by BreastQ after 6, 24, and 36 months, the feasibility, efficacy, safety of the heterologous complete resorbable TIGR-Matrix in prepectoral implant-based breast reconstructive surgery. This includes the number and rate of occurrence of adverse events and a tabular list of adverse events that have occurred; cosmetic result reported by doctor and patient.Primary Measurements: Comparison of the pre- and postoperative (12 months) mean score of the BreastQ category “breast satisfaction” (well-being-breast); Patient-Reported-Outcome (PRO) measured with the specific questionnaire for breast reconstruction BreastQ 12 months after surgery.Secondary measurements: Comparison of the pre- and postoperative (6, 12, 24, 26 months) mean score of the BreastQ category “breast satisfaction” (well-being-breast); Means scores of all BreastQ categories pre- and postoperatively after 6, 12, 24, 36 months. Complication rate: defined as major complications, minor complications; specific complications, such as seroma-volume, need for aspiration in symptomatic patients and number of aspirations in postoperative follow up, reconstructive failure (defined as unplanned implant loss), cosmetic outcome (domains of cosmesis of BreastQ) and rate of unplanned conversion operations (to mastectomy without reconstruction; to mastectomy with reconstruction; to autologous reconstruction).Current status:20 patients are recruited.First Interim analysis planned: 40 evaluable patients with 6 months FU data availableNo uncommon complications.Sponsor: AWOgynFunding: Novus Scientific

W. Chen, B. Zhu, J. Xue, L. Zheng; Department of Breast Surgery, Changzhou No.2 People’s Hospital, the Third Affiliated Hospital of Nanjing Medical University, Changzhou, CHINA.

Background: Granulomatous lobular mastitis (GLM) is characterized by nonspecific chronic inflammation concentrated in breast lobules. Surgical resection is one of the most common treatment options for GLM. Here we report our 1-year experience with a new treatment approach for GLM that involves the use of a lateral intercostal artery perforator (LICAP) flap. Methods: During March 2024 to May 2024, we enrolled 20 GLM patients who underwent breast surgery with the use of LICAP flap. All patients were women; most of the patients were 18-50 years old; and all the clinical manifestation of GLM was breast mass. Then, we evaluated operative data (time, blood loss, and intraoperative complications), primary healing time, and recurrence, and we also analyzed the safety of day-case surgery and patient-reported outcomes (cosmetic outcome, and improvement in dressing change and bathing) at 12 months. We recorded the occurrence of common postoperative complications of the breast and documented the follow-up conditions with photographs. Results: Median age of the patients was 42 years (range: 27 to 50 years). Duration of GLM was about 1 month, and median size of the lesions was 4.75 cm (range: 3.6 to 8 cm). No significant intraoperative complications occurred. All wounds healed by primary intention. The patients’ satisfaction with the breast shape was as follows: excellent (85%), good (15%), acceptable (0%), and poor (0%). No recurrence was recorded. Day-case surgery was proven to be safe and feasible, and could reduce hospital stay. Conclusion: For GLM patients refractory to conservative therapy or former unsatisfactory surgical management whose lesion is larger than 3 cm, LICAP is a suitable approach to fill the post-operation defect and achieve a relatively satisfactory cosmetic outcome.

W. Chen, Y. Jini, P. Liwei, N. Chao, H. Jian; Department of Breast Surgery, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, CHINA.

Background: Accurate axillary staging after neoadjuvant chemotherapy (NAC) in initially node-positive breast cancer remains controversial, particularly in settings where radioisotopes are unavailable. We prospectively evaluated the performance of single-blue-dye sentinel lymph node biopsy (SLNB) combined with clip-guided targeted axillary dissection (TAD).Methods: Consecutive patients with biopsy-proven cN1-2 disease received standard NAC. The biopsy-positive node was clipped prior to treatment. During surgery, 2-4 mL of methylene blue was injected peritumorally; all blue-stained nodes were resected as sentinel lymph nodes (SLNs), followed by selective excision of the clipped (marked) node. Completion axillary lymph node dissection was performed only in cases where residual nodal disease was identified. The primary endpoints were the SLN identification rate (IR), concordance of pathologic status between the marked lymph node (MLN) and SLNs, and the false-negative rate (FNR; negative SLNs with metastasis in non-SLNs).Results: Twenty-nine women (median age 48 years; range, 31-68 years) were enrolled between July 2022 and February 2024. SLNs were successfully identified in 28/29 patients, yielding an IR of 96.6% (95% CI 82.8-99.4). The MLN was retrieved as an SLN in 28/29 cases (96.6 %), and it constituted the first SLN removed in 19/28 (67.9 %). Residual nodal disease was present in 11/29 patients (37.9%). One of these 11 patients had negative SLNs but positive non-SLNs, leading to an overall FNR of 9.1% (1/11; 95% CI 0-41.3). Nodal pathological complete response (pCR) rates varied by molecular subtype: 90% in triple-negative tumors, 66.7 % in HER2-positive tumors, and 44.4 % in HR+/HER2-negative tumors. No dye-related adverse events were observed.Conclusions: The combination of single-blue-dye SLNB and clip-guided TAD demonstrated a high identification rate, excellent MLN-SLN concordance, and FNR below the 10% benchmark. This pragmatic and minimally invasive approach provides a reliable alternative to routine axillary lymph-node dissection in post-NAC patients when dual tracers or radioisotopes are unavailable.

R. Mukherjee¹, S. K. Pattashanee¹, B. K. Singh¹, A. Krishna¹, S. Soren¹, D. Kandasamy², S. V¹; ¹Department of Surgical Disciplines, All India Institute of Medical Sciences, New Delhi, Delhi, INDIA, ²Department of Radiology, All India Institute of Medical Sciences, New Delhi, Delhi, INDIA.

INTRODUCTION: Breast cancer surgery has shifted towards breast conservation surgery. Perforator-based flaps play a pivotal role. The thoracodorsal artery perforator-based (TDAP) flap is one such. In TDAP, varied amount of skin and subcutaneous fat can be used. It can reach any quadrant of the breast. It can even be converted to a musculocutaneous flap, if a larger volume is required. In this study, the anatomical and vascular basis of TDAP were analysed using computed tomography angiographic (CTA) and cadaveric dissection (CD). METHODS: A prospective observation study was carried out over 2 years in AIIMS, New Delhi. TDAP was dissected in 10 cadavers (20 sides). As part of metastatic workup, CTA was done in 23 locally advanced breast cancer (LABC) patients along with bone scan. Fresh, Theil cadavers, cadavers ≥ 18 years of age, and female BC patients >18 years were included. Injury/ scarring of chest wall, previous axillary surgery and cadavers/ patients <18 years were excluded. Primary objective was to determine course, precise localization and diameter of TDAPs. Secondary objective was to analyse and compare pattern of distribution of TDAPs: Dominant (DP) and Non-Dominant (NDP), in CD and CTA. Perforators were marked in sequence as TDAP 1, 2, 3 and so on. Analysis parameters of TDAP, in CD and CTA were distance from apex of axilla, distance from anterior border of latissimus dorsi (LD), diameter of perforator at its entry into muscle and perforator’s length. DPs and NDPs were analysed. Data was recorded in MS Excel and analysed in SPSS v23. Descriptive statistics were elaborated as means/standard deviations, medians/IQRs for continuous variables. Frequencies and percentages for categorical variables, group comparisons of continuously distributed data using independent sample ‘t’ test, Chi-squared test for group comparisons of categorical data, Paired t-test for paired analysis for continuous variables and Wilcoxon Signed Rank test for non-parametric data were used. RESULTS: A total of 52 TDAPs (20 in males and 32 in females) in cadavers and 57 TDAPs in 23 LABC patients were identified. Spatial distribution-wise (CD), 20 (38.5%) were TDAP1, 20 (38.5%) were TDAP2 and 12 (23.1%) TDAP3. From CTA, 45 (78.9%) were TDAP1 and 8 (14%) were TDAP2. Only 2 perforators were found as TDAP 3 and 4 in CTA. At least 1 DP was identified in CD and CTA. TDAP detection frequency and distance from the anterior border of LD were more in CD. In CD and CTA, the mean length of TDAP and distance from the apex of the axilla were comparable. The diameter of the perforator was significantly more in CTA. Table 1 shows the comparison of CTA and CD findings (significant ones).

CONCLUSION: TDAPs have a consistent distribution pattern, adequate length and vessel calibre, when analysed in CD and CTA. The anatomical and vascular basis of TDAP (DPs and NDPs) are important for better perforator-based reconstructions.

M. Tomiguchi, K. Hidaka, L. Goto-Yamaguchi, Y. Yamamoto; Breast and Endocrine Surgery, Kumamoto University Hospital, KUMAMOTO, JAPAN.

Background; Although the Japanese Breast Cancer Clinical Practice Guideline (2022) allow immediate breast reconstruction (IBR) after neoadjuvant chemotherapy (NAC) with caution, concerns remain regarding delayed would healing, increased surgical complications, and unknown oncologic safety. We aimed to evaluate the safety and oncologic outcomes of IBR following NAC by comparing patients with and without NAC at our institution. Methods: We retrospectively reviewed 228 breast reconstructions performed at the time of mastectomy from July 2013 to September 2024. Of these, 29 breasts (13.0%) underwent IBR after NAC (NAC group), and 194 breasts (87.0%) were reconstructed without NAC (control group). We analyzed clinicopathological characteristics, operative time, blood loss, length of hospital stay, postoperative complications, recurrence, and survival. Median follow-up was 73 months (range, 3-134). Results: Patient age and surgical procedures (including nipple-sparing mastectomy rates: 41.4% vs 44.3%) were comparable. Autologous reconstruction was more frequent in the control group (27.3% vs 10.3%, p=0.06). No significant differences were observed in: operative time: 254 vs 271.5 min (p=0.71), blood loss: 65 vs 63 mL (p=0.71), hospital stay: 13 vs 14 days (p=0.26), overall complication rate: 37.9% (NAC) vs 30.4% (control) (p=0.42), major complications requiring reoperation: 13.3% vs 13.0% (p=1.00). Local recurrence occurred in 1 (3.4%) vs 7 (3.6%) cases (p=1.00). Distant recurrence was significantly more common in the NAC group (17.2% vs 0.52%, p=0.0005), as was breast cancer-specific mortality (10.3% vs 0%, p=0.002). These outcomes likely reflect the higher baseline recurrence risk of the NAC group. Conclusions: Immediate breast reconstruction following NAC was not associated with increased surgical risk. Although oncologic outcomes were worse in the NAC group, this is likely attributable to patient selection with inherently higher recurrence risk. With proper patient counseling and risk stratification, IBR after NAC can be considered a safe and feasible option. Further prospective studies incorporating patient-reported outcomes are warranted.

C. YAMANAKA, S. MATSUZAKI, Y. HAYAKAWA, H. MANABE, M. KUBOTA, T. ITO, Y. KOMOIKE; Department of Surgery, Kindai University, Osaka, JAPAN.

Background: Radiofrequency ablation (RFA) for early-stage breast cancer with tumors ≤15 mm in diameter was approved for coverage under Japan’s national health insurance in December 2023, following favorable results from several clinical trials. Clinical RFA procedures commenced at our institution in May 2024. Small early-stage breast cancers—especially non-mass lesions—are often difficult to visualize or delineate using conventional B-mode ultrasound (US) alone. Additionally, gas formation during RFA may obscure the lesion, complicating precise localization for additional ablation. This study aimed to evaluate the clinical utility of fusion imaging combining contrast-enhanced breast magnetic resonance imaging (MRI) with US and/or contrast-enhanced US (CEUS) to improve lesion targeting and procedural accuracy during RFA. Patients and Methods: Fourteen patients with early-stage breast cancer underwent RFA guided by fusion imaging. A volume navigation system (LOGIQ E10x, GE Healthcare) was used to fuse dynamic contrast-enhanced MRI with US, aligning anatomical landmarks such as the nipple to ensure accurate lesion localization. CEUS using Sonazoid® was performed to evaluate intratumoral microvascularity. A Cool-tip needle (Medtronic, CO, USA) was inserted with a planned 1-cm safety margin around the tumor. Intratumoral impedance was measured upon insertion, and 10-20 mL of 5% glucose was injected into the retromammary space to prevent heat diffusion. Ablation was initiated at 5 W and continued until automatic roll-off occurred, due to increasing impedance. Therapeutic efficacy was assessed ≥4 weeks post-procedure using follow-up imaging and ultrasound-guided vacuum-assisted biopsy (US-VAB) of the ablation zone. Results: Patient ages ranged from 34 to 82 years (mean: 57 years), with tumor sizes from 7 to 15 mm (mean: 12.4 mm). Histopathologic findings included ductal carcinoma in situ (DCIS; n=8) and invasive ductal carcinoma (IDC; n=6). Molecular subtypes included Luminal A-like (n=4) and Luminal B-like (n=2). Tumors were located in the upper outer quadrant (n=8), upper inner quadrant (n=2), lower outer quadrant (n=2), and deep medial or axillary tail regions (n=1 each). Fusion imaging significantly improved visualization and delineation of lesions that were challenging to identify with B-mode US alone. It also enabled accurate re-localization of the original lesion during additional ablation sessions, resulting in successful complete ablation in all cases. Initial impedance ranged from 116 to 245 Ω (mean: 169 Ω), maximum ablation temperature from 83°C to 100°C (mean: 93°C), and ablation time from 14 to 32 minutes (mean: 20 minutes). One case of postoperative nipple retraction was observed; no other major complications occurred. No viable cancer cells were detected in any US-VAB specimens. Conclusion: Fusion imaging combining contrast-enhanced MRI with US/CEUS enhances the precision, safety, and efficacy of RFA for early-stage breast cancer, particularly for lesions that are poorly visualized on conventional US. Further accumulation of clinical cases is needed to standardize fusion imaging protocols and optimize outcomes.

A. O. Gorina¹, P. V. Krivorotko¹, A. S. Emelyanov¹, D. A. Enaldieva¹, E. K. Zhiltsova¹, L. P. Gigolaeva¹, T. T. Tabagua¹, A. V. Komyakhov¹, V. V. Mortada², P. S. Pesotsky¹, D. G. Ulrikh¹, N. S. Amirov¹, V. F. Semiglazov¹; ¹The department of breast tumours, FSBI “N.N. Petrov National Medical Research Center of Oncology” of the Russian Ministry of Health, Saint Petersburg, RUSSIAN FEDERATION, ²The department of oncology and reconstructive plastic surgery, FSBI “N.N. Petrov National Medical Research Center of Oncology” of the Russian Ministry of Health, Saint Petersburg, RUSSIAN FEDERATION.

BackgroundThe indications for and extent of axillary surgery in breast cancer have evolved significantly over the past two decades and remain an area of active research and debate. Sentinel lymph node biopsy (SLNB) is currently the standard approach for axillary staging in patients with early-stage breast cancer. However, emerging data suggest that axillary surgery may be safely omitted in select patients aged ≥60 years with early-stage, luminal A, clinically node-negative breast cancer. This prospective study aimed to assess the applicability of this strategy in patients with hormone receptor-positive (HR+), HER2-negative (HER2−) tumors. MethodThis prospective study included 100 patients diagnosed with cT1-2N0M0, HR+HER2- breast cancer (BC) who underwent combined treatment from 2023 to 2025 at the FSBI «N.N.Petrov National Medical Research Center of Oncology» of the Russian Ministry of Health. All patients had clinically negative axillary lymph nodes confirmed via ultrasound, mammography and mammoscintigraphy/breast molecular imaging with 99mTc-MIBI. Surgical axillary staging was omitted in this patient population. Preoperative sentinel lymph node localization for adjuvant radiation treatment planning was performed using single-photon emission computed tomography (SPECT) lymphoscintigraphy. ResultsAmong 100 patients with cT1-2N0M0 HR+HER2- breast cancer median age was 67 [59; 86] years. Median tumor size was 15 [4; 30] mm and tumors were grade 1 or 2. Estrogen receptor (ER) expression ranged from 90-100% in 95 cases and 70-80% in 5 cases. Progesterone receptor (PR) expression was 0-10% in 17 cases, 20-40% in 4, and 60-100% in 79. The Ki-67 proliferation index was 1-10% in 29 cases, 11-20% in 46, and 21-30% in 25. Histological subtypes included 94 cases of invasive carcinoma of no special type (NST), 3 – lobular carcinomas, and 3 – mucinous carcinomas. All patients in the study received adjuvant radiotherapy, administered in hypo- or ultra-hypofractionation regimens at the discretion of the radiation oncologist for breast and sentinel lymph nodes. Specifically, 15 patients received a 5-fraction regimen, 50 patients received 15 fractions, 35 patients received 16 fractions, and 2 patients underwent high-dose brachytherapy additionally. Adjuvant hormone therapy was recommended for all patients: 79 received Aromatase Inhibitors and 21 received Tamoxifen. No patient was recommended to receive adjuvant chemotherapy. ConclusionWe believe that these findings support careful implementation of omission of surgical staging of the axilla in postmenopausal patients with cT1-2N0, HR+HER2− breast cancer and a negative axillary lymph nodes. At our institution, this approach is currently implemented in patients over 59 years of age with ECOG performance status 20%, and Ki-67 index <30%.

J. D. Prado¹, S. A. Fialho², A. V. Silva¹, J. Moraes³, A. A. Vasconcelos⁴, G. R. Donald⁵, I. C. Rocha⁵, C. F. Monteiro¹, V. V. Pignataro¹, R. J. Vieira⁶, C. E. Barbosa²; ¹Breast Surgery, Hospital Universitário Antônio Pedro (HUAP-UFF), Niterói, BRAZIL, ²Maternal and child care – Gynecology discipline, Universidade Federal Fluminense, Niterói, BRAZIL, ³Statistics Department, Universidade Federal Fluminense, Niterói, BRAZIL, ⁴Diagnostic imaging unit, Hospital Universitário Antônio Pedro (HUAP-UFF), Niterói, BRAZIL, ⁵Oncology and Hematology, Hospital Universitário Antônio Pedro (HUAP-UFF), Niterói, BRAZIL, ⁶Gynecology Department, Fundacao Oswaldo Cruz, Rio de Janeiro, BRAZIL.

Introduction: Breast cancer is the second most common malignancy in women worldwide after non-melanoma skin cancer and remains the leading cause of cancer-related mortality in this population. In Brazil, approximately 74,000 new cases are projected annually through 2025. Sentinel lymph node biopsy is the standard axillary management for early-stage breast cancer. However, emerging evidence suggests that patients with negative preoperative axillary involvement may not benefit significantly from axillary surgery.Objective: The aim of this study was to determine if the preoperative assessment can identify patients with absent or low axillary tumor burden who could safely omit sentinel lymph node biopsy during surgical treatment of luminal/HER2-negative breast cancer.Methods: We conducted a prospective observational study at a public university hospital operating within the Brazilian National Health System (SUS). Eligible candidates were women with early-stage (T1-T2 N0) luminal/HER2-negative breast cancer who exhibited no clinical or ultrasonographic evidence of axillary disease on preoperative assessment and subsequently underwent sentinel lymph node biopsy. Histopathological findings from surgery specimens were then correlated with the clinicopathological parameters during preoperative assessment.Results: Among the 40 participants, 12 (30%) exhibited axillary involvement, and none demonstrated extensive axillary disease (≥ 4 positive lymph nodes). The absence of tumor lymphovascular invasion was significantly associated with a negative axillary status (OR = 9.286; p = 0.018). Age ≥ 60 years was also associated with a negative axilla, although at a 10% significance level (OR = 3.5; p = 0.082).Conclusion: Negative preoperative axillary assessment is an effective strategy for selecting patients without extensive axillary disease in luminal/HER2-negative breast cancer. The absence of lymphovascular invasion and age ≥ 60 years increase the likelihood of a negative axilla. Clinicopathological parameters in early-stage luminal/HER2-negative breast cancer appear to provide sufficient data for selecting candidates for omission of sentinel lymph node biopsy, especially when the presence of low axillary tumor burden does not influence systemic therapy choice.Keywords: Sentinel lymph node biopsy; Breast cancer; Invasive ductal carcinoma; Sentinel lymph node; Lymphatic metastasis. Table: Logistic regression results for estimating the probability of a negative axillary status.

Y. Jung Dug¹, T. Park¹, H. Cho¹, Y. Chang¹, M. Kim², J. Shin², J. Lee¹, J. Lee³, H. Park³, T. Jung⁴; ¹Department of Plastic and Reconstructive Surgery, School of Medicine, Kyungpook National University, Daegu, KOREA, REPUBLIC OF, ²Department of Applied Biosciences, Kyungpook National University, Daegu, KOREA, REPUBLIC OF, ³Department of Surgery, School of Medicine, Kyungpook National University, Daegu, KOREA, REPUBLIC OF, ⁴Department of Physical Medicine and Rehabilitation, School of Medicine, Kyungpook National University, Daegu, KOREA, REPUBLIC OF.

Despite the implication of bacterial biofilms in the etiology of capsular contracture, there is limited research on the microbial structure of the biofilm in patients with capsular contracture. Moreover, the potential role of the skin microbiome in capsular contracture remains undefined. Therefore, we conducted this study to characterize the microbiome of the breast capsular contracture by comparing it with the microbiome of biofilms without capsular contracture. We also investigated the associations between the microbial structures of the skin surrounding the breast and those of the breast capsule. We collected 25 capsules, including 14 samples from biofilms without capsular contracture and 11 samples from biofilms with capsular contracture. Beta diversity analysis demonstrated that the microbial structures in biofilms were distinctly different from those in the skin. The microbial composition of the biofilms was more influenced by individual variation than by the progression of the capsular contracture. Biofilms with capsular contracture showed a higher relative abundance of Staphylococcus, correlating positively with total bacterial load. Capsular contracture is associated with an escalation in total bacterial load and an increase in the abundance of opportunistic pathogens, such as Staphylococcus. This comparative analysis of biofilms in contracted breast capsules emphasizes the management of pathogens, considering bacterial load, in the occurrence of capsular contracture.

S. Lee; Division of Breast Surgery, Samsung Medical Center, Gangnam-gu, Seoul, KOREA, REPUBLIC OF.

Background Robot-assisted nipple-sparing mastectomy (R-NSM) was developed to minimize visible scarring and improve the quality of life in breast cancer patients. However, despite its increasing adoption, data on its oncologic outcomes remain limited. This study aimed to compare the oncologic outcomes of R-NSM and conventional nipple-sparing mastectomy (C-NSM). Methods We retrospectively reviewed patients who underwent NSM with immediate breast reconstruction (IBR) for breast cancer between 2019 and 2022. Risk-reducing cases were excluded. R-NSM and C-NSM groups were compared after 1:5 propensity score matching using nearest-neighbor methods (caliper = 0.2). Results After 1:5 propensity score matching, most clinicopathologic variables were well balanced between groups. The median follow-up duration was 37.5 months for the R-NSM group and 42.6 months for the C-NSM group. No locoregional recurrence, distant metastasis, or death occurred in the R-NSM group. All oncologic events occurred in the C-NSM group, including 3 locoregional recurrences (1.5%), 3 distant metastases (1.5%), and 7 total recurrences (3.5%). Kaplan-Meier analysis showed no statistically significant differences in LRFS (p = 0.162), DMFS (p = 0.255), or DFS (p = 0.050), though all adverse events occurred in the C-NSM group. Event-based comparison revealed a significantly better DFS for R-NSM (p = 0.002). In multivariable Cox analysis, older age (HR = 0.14, p = 0.040) and positive nodal stage (N1: HR = 4.7; N3: HR = 31.9, p = 0.042) were associated with increased recurrence risk. R-NSM showed a lower recurrence hazard in univariable analysis (HR = 0.12, p = 0.177). Conclusion R-NSM showed oncologic outcomes comparable to those of conventional NSM, with no recurrence or mortality observed despite longer follow-up. These results support R-NSM as a safe and effective surgical option for appropriately selected breast cancer patients.

A. A. Fornazari¹, I. Rabinovich¹, A. Sebastião¹, S. Boscoli², I. C. Soares¹, J. M. Jakobson³, E. M. Kac³, F. Cohene³, C. de Souza³, C. Urban⁴, C. Spautz⁴, K. F. Anselmi⁴, F. F. Kuroda⁴, M. T. Doria⁴, L. P. Nissen⁴, E. T. Schunemann⁴, R. S. Lima⁴; ¹Universidade Federal do Paraná, Hospital de Clínicas, Curitiba, BRAZIL, ²Pathology, Hospital Universitário Evangélico Mackenzie, Curitiba, BRAZIL, ³Medicine, Universidade Federal do Paraná, Curitiba, BRAZIL, ⁴CDM, Centro de doenças da mama de Curitiba, Curitiba, BRAZIL.

Background/Objective: Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) is associated with improved event-free and overall survival, particularly in triple-negative and HER2-positive breast cancer. Tumor-infiltrating lymphocytes (TILs) are promising prognostic and predictive biomarkers, correlating with higher pCR rates in these subtypes. However, the clinical relevance of TILs variation before and after NAC remains unclear. This study aimed to investigate associations between TILs variation, pCR, Residual Cancer Burden (RCB), and pre-NAC TILs with clinical outcomes. Methods: Retrospective cohort of 302 patients treated with NAC followed by surgery at two tertiary centers in Curitiba, Brazil, from 2016 to 2020. Data were extracted from electronic medical records. Pre-NAC core biopsies and post-NAC surgical specimens were reviewed by a dedicated breast pathologist. TILs were assessed per International TILs Working Group guidelines, and analyzed as categorical variables (low ≤10%, intermediate 11-49%, high ≥50%). Post-NAC TILs were quantified in stroma adjacent to the residual tumor bed. Pathologic response was defined using the RCB classification. Statistical analysis included the Wilcoxon signed-rank and Stuart-Maxwell tests. ROC curves identified outcome-related cut-offs. Results: Of 302 patients, 30% achieved pCR (Table 1). TILs were evaluated in 183 paired samples. TILs levels significantly declined post-NAC (p25% were associated with reduced distant recurrence risk. No significant association was found with locoregional recurrence or mortality (Table 2). Conclusion: TILs declined after NAC, particularly in pCR cases. Pre-NAC TILs >25% were linked to lower risk of distant recurrence, supporting their prognostic value in the neoadjuvant setting.

T. Jordan, D. L. Rimm, H. Zhan; Pathology, Yale New Haven Hospital, New Haven, CT.

Objective: A subset of invasive lobular carcinoma (ILC) is managed with neoadjuvant therapy (NAT). The clinical and pathologic features of ILC following NAT are not well characterized. The aim of this study is to characterize the pathologic response in patients with ILC treated with NAT, including neoadjuvant endocrine therapy (NET), neoadjuvant chemotherapy (NCT), and Herceptin-targeted NCT (H-NCT). Methods: We conducted a retrospective cohort study of 65 patients with ILC and 290 patients with invasive ductal carcinoma (IDC) who received neoadjuvant therapy followed by resection between 2019 and 2024. Clinicopathologic parameters were recorded, including age, tumor grade, histologic type, staging, ER, PR, and HER2 status. Residual cancer burden (RCB) was evaluated on the post NAT resection specimens through an  online calculator  (www.mdanderson.org/breastcancer_RCB). Cases were categorized into three subtypes: ER+/HER2-, HER2+, and triple negative. Statistical analyses were performed to compare ILCs and IDCs with the same immunohistochemical (IHC) profiles. Results: Patients with ER+/HER2- and HER2+ ILCs were older at diagnosis compared to those with ER+/HER2- and HER2+ IDCs (p<0.01). Among patients with ILCs, 41 (63%) had ER+/HER2- tumor and received NET or NCT, 6 (9%) had triple negative tumor and received NCT only, and 18 (28%) had HER2+ tumor and received H-NCT. The pathologic complete response (pCR) rate was 44% in HER2+ ILCs and 60% in HER2+ IDCs. No pCR was achieved in triple negative and ER+/HER2- ILCs and IDCs. The majority of ER+/HER2- ILCs (87%) and all triple negative ILCs (100%) were classified as RCB II or RCB III, comparable to IDC cases with the same immunohistochemical subtypes (Table 1). Conclusion: ILCs demonstrated a similar response to neoadjuvant therapy as IDCs when matched by IHC subtype. These findings suggest that the effectiveness of neoadjuvant therapy is primarily determined by IHC-based tumor subtype rather than histologic subtype.

Y. Hara¹, R. Yamaguchi², M. Matsumoto¹, M. Oshi³, S. Urakawa¹, A. Tanaka¹, M. Akashi⁴, S. Kuba⁴, R. Otsubo¹, S. Eguchi⁴, K. Matsumoto¹; ¹Department of Surgery, Division of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JAPAN, ²Department of Diagnostic Pathology, Nagasaki University Hospital, Nagasaki, JAPAN, ³Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, JAPAN, ⁴Department of Surgery, Division of Digestive Surgery and Transplantology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JAPAN.

[Introduction] Mucinous carcinoma (MC) of the breast is histologically defined by the World Health Organization as either pure (comprising >90% mucinous component) or mixed (comprising 10-90% mucinous component) subtypes. Typically, the tumor nests within MC display conventional cluster morphology or invasive micropapillary carcinoma (IMPC) architecture. Intriguingly, some MCs contain hypercellular solid nests with neuroendocrine features that closely resemble solid papillary carcinoma (SPC), a distinct entity characterized by mucin production and fibrovascular cores. Given the overlapping morphological and secretory features between SPC and some forms of MCs, we hypothesized that a subset of MCs may arise from or share a lineage with SPC. To explore this, we stratified MCs based on the presence or absence of SPC-like histological features and conducted a comprehensive molecular characterization using data from The Cancer Genome Atlas Breast Invasive Carcinoma Collection (TCGA-BRCA). This study aims to elucidate the biological distinctions between SPC-related and non-SPC MC subtypes, potentially refining our understanding of MC heterogeneity and its clinical implications. [Material & Method] We systematically re-evaluated all available hematoxylin and eosin (H&E) digital slides from the TCGA-BRCA cohort (n=1084). Tumors exhibiting >10% mucinous component were selected and subclassified into two groups based on histopathological features: those with a SPC component (MC-SPC) and those without a SPC component, including IMPC patterns (MC-OTHER). Clinicopathological parameters were collected and compared between the groups using the chi-square or Fisher’s exact test, as appropriate. To explore transcriptional differences, differentially expressed genes (DEGs) were identified using a false discovery rate-adjusted p-value 1. DEGs were visualized using principal component analysis (PCA), volcano plots, and heatmaps. Functional enrichment analyses were performed using the clusterProfiler R package, referencing the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. R (version 4.4.3) was used for all statistical analyses. [Result] We identified 29 mucinous carcinoma cases from the TCGA-BRCA cohort with > 10% mucinous component, including 18 with MC-SPC and 11 with MC-OTHER. The median age was 67.5 years (range, 41-85) in the MC-SPC group and 55 years (range, 38-79) in the MC-OTHER group. There was no significant difference in age between the two groups (p = 0.16). The HER2-positive subtype was significantly more frequent in MC-OTHER compared to MC-SPC (p = 0.014). Transcriptomic analysis revealed distinct molecular profiles between the two groups, as demonstrated by volcano plots and a heatmap of the top 30 differentially expressed genes, although PCA did not show clear separation. Functional enrichment analysis showed that MC-OTHER tumors exhibited upregulation of pathways related to extracellular matrix (ECM) organization and cell adhesion, suggesting a more mesenchymal-like phenotype. In contrast, MC-SPC tumors were enriched for pathways associated with synaptic signaling and neurotransmitter transport, reflecting potential neuroendocrine-associated biology. [Conclusion] This study identifies two transcriptionally distinct subtypes of mucinous carcinoma, MC-SPC and MC-OTHER, based on histopathological features. These subtypes exhibit divergent biological characteristics, including mesenchymal-like features in MC-OTHER and neuroendocrine-associated pathways in MC-SPC. This subclassification may have clinical relevance and warrants further investigation in larger cohorts.

N. Abele¹, M. Berner¹, R. Stöhr¹, H. Arndt¹, C. Mawrin², R. Erber³; ¹Institute of Pathology, University Erlangen, Erlangen, GERMANY, ²Institute of Neuropathology, University Magdeburg, Magdeburg, GERMANY, ³Institute of Pathology, University Regensburg, Regensburg, GERMANY.

Introduction: Breast cancer brain metastasis (BCBM) represents a significant clinical challenge with poor prognosis. Certain breast cancer subtypes, notably HER2-positive and triple-negative breast cancer (TNBC), are associated with a higher risk of brain metastasis. Understanding these unique properties, distinct from primary tumors, is crucial for therapeutic strategies. In this study, we aimed to characterize key biomarkers in BCBM to enhance understanding of their distinct molecular and immunological profiles. Methods: We retrospectively evaluated 36 intracranial BCBM from 36 patients for hormone receptor (ER/PR), HER2-status (including HER2-low and -ultra-low), proliferation (Ki-67), PD-L1 expression, tumor-infiltrating lymphocytes (TILs) as well as PIK3CA mutations. Biomarker frequencies were compared against published data from primary breast cancer cohorts (TCGA, METABRIC, SEER, KEYNOTE-355). Results: The BCBM cohort exhibited a significantly skewed subtype distribution compared to primary breast cancer. While primary breast cancer is predominantly HR+/HER2- (Luminal A/B HER2-) (approx. 74.4%), this subtype comprised only 16.7% (6/36) of our BCBM cases. Conversely, TNBC (44.4%, 16/36) and HER2-positive subtypes (38.9%, 14/36) were notably overrepresented in our cohort compared to their prevalence in primary breast cancer (approx. 11.4% and 14.2%, respectively). This significant difference suggests a differential propensity for brain metastasis among subtypes and is in line with previous findings. The overall mean Ki-67 was 42.6% and most cases (88.9%, 32/36) showed high proliferation (Ki-67 ≥ 20%), with 75.0% (27/36) demonstrating very high proliferation (Ki-67 ≥ 30%). Subtype-specific Ki-67 levels generally reflected the expected proliferative activity of corresponding primary breast cancer subtypes. PD-L1 expression (22C3, CPS ≥ 10%) was very low, found in only 2.8% (1/36) of cases. A slightly larger subset (8.3%, 3/36) met the IC positivity criterion (IC ≥ 1%) with SP142. This low prevalence of actionable PD-L1 expression in BCBM contrasts sharply with the higher rates observed in primary TNBC (e.g., 38% for CPS ≥ 10% in KEYNOTE-355). Furthermore, TILs were significantly lower compared to primary breast cancer and across all subtypes; only 5.9% cases had high TILs (>=60%) compared to the 19% for primary found in literature. This suggests a very different tumor microenvironment for metastasis to the CNS, with implications for immunotherapy efficacy. PIK3CA analysis revealed 20% (6/30) of cases with mutations and no significant deviation from the expected frequencies in respect of the molecular subtype. Conclusion: Our findings indicate that BCBMs exhibit a distinct molecular landscape characterized by an enrichment of TNBC and HER2-positive subtypes with high proliferation (Ki-67). PD-L1 expression and TILs appears to be markedly lower than in primary breast cancer, especially in TNBC. These insights highlight the unique biology of BCBM, emphasizing the need for biomarker analysis on metastatic tissue to guide personalized therapeutic strategies.

R. Otsubo¹, Y. Hara¹, S. Urakawa¹, A. Tanaka¹, M. Akashi¹, S. Kuba¹, M. Matsumoto¹, R. Yamaguchi², K. Matsumoto¹; ¹Surgery, Breast and Endocrine Surgery, Nagasaki University Hospital, Nagasaki, JAPAN, ²Pathology, Nagasaki University Hospital, Nagasaki, JAPAN.

Background:The semi-dry dot-blot (SDB) method is a diagnostic technique used to detect lymph node (LN) metastases by identifying cytokeratin (CK) proteins in the lavage fluid of sectioned LNs. This method is based on the principle that CK, an epithelial marker, is absent in normal lymphatic tissue. We prospectively evaluated novel SDB kits incorporating a newly developed anti-CK19 antibody and an automatic reader for diagnosing LN metastases in breast cancer patients. In a previous analysis of 1734 sentinel LNs (SLNs) from patients not receiving neoadjuvant chemotherapy (NAC), the kit demonstrated a sensitivity of 93.0%, specificity of 97.1%, and overall agreement of 96.7% for detecting macrometastases (>2.0 mm). However, the impact of NAC—especially in triple-negative and HER2-positive subtypes—on the diagnostic performance of the SDB method remains unclear, given that chemotherapy can cause cancer cell degeneration. This study aimed to evaluate whether the SDB kit could accurately detect macrometastases in patients undergoing NAC. Methods:A total of 127 LNs were collected from 74 breast cancer patients who underwent NAC followed by surgery between May 2022 and December 2024 at Nagasaki University Hospital. Both patients with and without axillary LN metastases were eligible. Eligible LNs were defined as all SLNs in patients who underwent SLN biopsy and two axillary LNs in patients who underwent axillary LN dissection. Each LN was sliced at 2-mm intervals and rinsed with phosphate-buffered saline. The resulting lavage fluid was centrifuged, and the cells were lysed to extract protein, which was then analyzed using the SDB kit and automatic absorbance reader. Pathologists, blinded to the SDB results, independently diagnosed LN metastasis using hematoxylin and eosin (H&E) staining. SDB-based diagnoses were compared with permanent histopathological diagnoses. Results:Among the 127 LNs, 56 were obtained via SLN biopsy and 71 via axillary LN dissection. Histological evaluation identified 16 macrometastases and 111 non-macrometastases (including 4 micrometastases and 1 case with isolated tumor cells). Using a CK19 absorbance cutoff of 11.9 milli-absorbance units (mAbs) for detecting macrometastases, the SDB kit correctly identified 15 of the 16 macrometastases and all 111 non-macrometastases. The resulting sensitivity, specificity, and overall agreement were 93.8%, 100%, and 99.2%, respectively. The single false-negative case involved a sparsely distributed residual tumor measuring 2.1 mm. The diagnostic process required approximately 20 minutes and cost less than USD 30 per kit. Conclusions:The novel SDB kits combined with an automatic reader provided rapid, accurate, and cost-effective detection of LN macrometastases without tissue loss, even after NAC. These findings support the potential utility of this method in clinical decision-making. A prospective multi-center study is planned to further validate clinical performance.

T. Jeon¹, Y. Sung², J. Lee², J. Oh¹, J. Ahn³, A. Kim¹; ¹Department of Pathology, Korea University Guro Hospital, Seoul, KOREA, REPUBLIC OF, ²Department of Pathology, Korea University Anam Hospital, Seoul, KOREA, REPUBLIC OF, ³Department of Pathology, Ewha Womans University Mokdong Hospital, Seoul, KOREA, REPUBLIC OF.

Background: Dysfunction of the E-cadherin/catenin complex is a hallmark of invasive lobular carcinoma (ILC) of the breast, which is associated with poorer long-term outcomes compared to invasive ductal carcinoma (IDC). However, accurate histologic diagnosis of ILC remains challenging due to complex morphologic and immunohistochemical (IHC) patterns. This study aimed to compare the expression patterns of E-cadherin, beta-catenin, and P120 catenin in breast carcinomas, focusing on aberrant patterns and their clinicopathologic significance. Methods: We retrospectively analyzed 264 breast carcinoma cases with suspected lobular morphology. Tissue microarray (TMA) blocks were constructed from surgical specimens. IHC for E-cadherin, beta-catenin, P120 catenin, N-cadherin, and P-cadherin was performed on TMA sections, and staining patterns were classified as membranous, aberrant, or loss. Results: Morphologically, 43 cases (16.3%) showed IDC features and 221 (83.7%) showed ILC features. After integrating IHC results, 18 cases (6.8%) were classified as IDC and 246 (93.2%) as ILC based on aberrant or loss of marker expression. The distribution of staining patterns was similar among E-cadherin, beta-catenin, and P120 catenin, with a high concordance (95.1%) between E-cadherin and beta-catenin. Beta-catenin demonstrated a distinct Golgi pattern in aberrant cases, enhancing interpretability and sensitivity compared to E-cadherin and P120 catenin. Interpretation of P120 staining was sometimes difficult due to the small size of lobular carcinoma cells and the presence of intracytoplasmic vacuoles. Twelve cases (4.5%) showed discordant results between E-cadherin and beta-catenin, with beta-catenin being more sensitive in detecting aberrant/loss patterns. Aberrant beta-catenin expression was significantly associated with higher N and M stage, higher histologic grade, lymphovascular invasion, lower estrogen receptor (ER) expression, higher HER2 expression, and increased N-cadherin and P-cadherin expression. Conclusions: Beta-catenin IHC is more sensitive and interpretable than E-cadherin or P120 catenin for distinguishing ILC from IDC, due to its unique localization patterns. Aberrant expression of adhesion complex molecules, especially beta-catenin, is associated with adverse clinicopathologic features and may reflect atypical features among breast carcinomas. These findings support incorporating beta-catenin IHC into the diagnostic workup of breast carcinomas with ambiguous morphology.

N. Amirov¹, N. Mikhaskova², P. Krivorotko¹, A. Kudaybergenova²; ¹Breast Tumor Department, NMRC of Oncology named after N.N. Petrov, Saint Petersburg, RUSSIAN FEDERATION, ²Pathology Department, NMRC of Oncology named after N.N. Petrov, Saint Petersburg, RUSSIAN FEDERATION.

Background: One of the important prognostic and predictive markers in the histological assessment of breast cancer (BC) after neoadjuvant therapy (NAT) is the Residual Cancer Burden (RCB) index. In the original formula developed by MD Anderson Cancer Center the linear dimensions of the tumor bed are taken into account, which makes it impossible to assess fragmented material, for example, when performing vacuum-assisted biopsy. Considering this limitation, an attempt was made to modernize the method for evaluating tumor response to NAT by recalculating the RCB index using the area of the tumor bed based on digital images (scans) of histological slides obtained from sectoral resections in patients with early-stage BC. Methods: A single-center retrospective study included 20 patients with ypT1a-cN0 stage breast carcinoma who had undergone neoadjuvant systemic therapy (FAC-T — 3 patients, AC-T — 8, AC — 2, DHP — 1, T — 2, EC+D+TRAST — 1, TCARB — 1, TCHP — 2) and were classified as RCB class 1. Digital scans of histological slides were obtained using the 3D HISTECH PANORAMIC 1000 scanner. Measurements of the tumor bed were carried out using two methods: traditional MD Anderson technique, which defines the tumor bed area with the assessment of the two largest dimensions of the tumor bed, and a modified in-house technique, which implies manual delineation of the entire area of tumor bed on the histological scans using a stylus within the 3D HISTECH SlideViewer 2.5.0 software. The measured areas were then used to recalculate the RCB index according to the original formula, which includes extracting the square root of the area. Results: The mean tumor bed area calculated using the MD Anderson method was 76.67 mm² (range: 14.2-258.7), whereas for the modified method, the mean was 153.65 mm² (range: 35.6-535). The mean RCB index for the standard method was 1.034 (range: 0.804-1.316), and for the modified method — 1.102 (range: 0.829-1.461). The obtained data was normally distributed in both groups. A high correlation was found between the two methods, indicating a high consistency between the methods (Pearson’s Correlation r = 0.96, p<0.001; Spearman’s Correlation ρ = 0.95, p<0.001). The mean difference in RCB index between two methods was 0.068 (95% CI: +0.040 to +0.096). According to the t-test, the difference between the two methods was statistically significant (p < 0.01). The modified method demonstrated systematically higher values of RCB index. Moreover, when applying the modified method, 2 out of 20 patients (10%) were reclassified from RCB class 1 to RCB class 2. Conclusion: The proposed modified method of tumor bed assessment correlates highly with the classical approach in calculating the RCB index. Larger studies are needed to determine the clinical significance of a persistent slight overestimation of the RCB index using the modified method.

A. Zhang¹, A. Cozzo², L. Olsson², E. Kirk², X. Gao², S. Nyante³, B. Calhoun¹, R. Vierkant⁴, M. Sherman⁴, M. Troester²; ¹Department of Pathology, UNC Medical School, Chapel Hill, NC, ²Department of Epidemiology, UNC Medical School, Chapel Hill, NC, ³Department of Radiology, UNC Medical School, Chapel Hill, NC, ⁴Department of Biostatistcs, Mayo Clinic, Rochester, MN.

Benign breast disease (BBD) confers elevated risk for breast cancer, yet current tools lack precision in identifying lesions likely to progress. Immune mechanisms may influence progression, but the spatial and molecular features of immune responses in BBD versus invasive cancer remain poorly characterized. We applied Digital Spatial Proteomics (DSP) to evaluate immune-related protein expression across 1,540 regions of interest (ROIs) from breast tumors (n=58, Carolina Breast Cancer Study [CBCS]), a UNC BBD cohort (n=20), and a Mayo BBD cohort (n=177). Using Consensus Clustering in CBCS and UNC BBD, we identified two stable immune phenotypes: “High Immune,” enriched in tumors and high-risk benign lesions, and “Quiet Immune,” predominant in low-risk BBD. ROIs were classified by immune marker expression, and patients were labeled as “High” if ≥50% of their ROIs were High Immune. In CBCS, High Immune profiles were associated with ER-negative status (OR=2.92 [0.99-8.65] participant-level; OR=3.28 [1.34-8.04] ROI-level). In BBD, High Immune profiles trended toward higher odds of high-risk lesions (OR=1.00 [0.15-6.70] participant-level; OR=1.68 [0.57-4.97] ROI-level), though this pattern was not replicated in the Mayo cohort. BBD samples exhibited substantial spatial heterogeneity in immune expression (40% within-patient ROI agreement vs. 74% in tumors), potentially limiting biomarker reliability. Nonetheless, four immune proteins (CD44, CD80, CD14, CD66b) were significantly associated with future cancer development in the Mayo cohort, though these findings require validation due to within-person variability. Our findings highlight the challenges posed by spatial heterogeneity in assessing immune biomarkers in BBD and suggest that immune activation may emerge later in disease progression. These results raise important questions about the timing and consistency of immune responses in the natural history of breast cancer.

M. Kubeczko¹, M. Mianowska-Malec¹, A. Polakiewicz-Gilowska¹, K. Swiderska¹, A. Lesniak¹, B. Lanoszka¹, B. Grandys¹, K. Chomik¹, N. Lisovska¹, B. Pycinski², E. Stobiecka³, J. Simek³, E. Chmielik³, A. Prat⁴, M. Jarzab¹; ¹Breast Cancer Center, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, POLAND, ²Faculty of Biomedical Engineering, Silesian University of Technology, Gliwice, POLAND, ³Tumor Pathology Department, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, POLAND, ⁴Cancer Institute and Blood Disorders, Hospital Clínic; Translational Genomics and Targeted Therapies in Solid Tumors, August Pi I Sunyer Biomedical Research Institute; Reveal Genomics; SOLTI Cancer Research Group; University of Barcelona, Barcelona, SPAIN.

Background: The TPH regimen (docetaxel, trastuzumab, pertuzumab) has long been the standard first-line treatment for HER2-positive metastatic breast cancer (MBC). However, recent findings from the DESTINY-Breast09 trial have challenged this paradigm, underscoring the need for predictive biomarkers to personalize treatment selection. Estrogen receptor positivity (ER+) may inform the use of CDK4/6 inhibitors, such as palbociclib, during the maintenance phase. While molecular classifiers—such as ERBB2 expression within the HER2Dx signature—have shown promise in identifying patients likely to benefit from prolonged TPH treatment, the prognostic potential of routinely available histopathological parameters remains insufficiently explored. This study aimed to evaluate whether histological grade, Ki67 proliferation index, and ER status predict progression-free survival (PFS) in patients receiving first-line TPH. Methods: We conducted a retrospective analysis of 134 female patients with de novo HER2-positive MBC, treated with first-line TPH between 2017 and 2024, all of whom had available breast tumor biopsy samples for histopathological evaluation. The median age was 60.2 years (range, 27.1-84.3 years). ECOG performance status was 0 in half of the patients, while the other half had a status of 1 or 2. Oligometastatic disease (OMD, ≤5 metastatic lesions) was present in 46.3%, liver metastases in 32.8%, and lung metastases in 24.6%. Histological grade was G1 in 2.2%, G2 in 44.8%, and G3 in 53.0%; G1 and G2 were grouped as G1-2. ER positivity was observed in 55.2% of cases, and the median Ki67 index was 32% (IQR: 20-60%). All evaluations were based on the initial breast tumor biopsy. Prognostic factors were assessed using Cox proportional hazards models; variables with p < 0.2 in univariate analysis were included in the multivariate model. Statistical significance was defined as p < 0.05. Results: The median PFS in the entire cohort was 38.3 months. Histological grade correlated strongly with outcome: patients with G1-2 tumors had a median PFS of 79.1 months versus 25.2 months for those with G3 tumors. The 2-year PFS rate was 71.2% (95% CI: 57.7-81.1%) for G1-2 and 52.1% (95% CI: 39.7-63.2%) for G3. In univariate analysis, G3 grade (HR 1.93; 95% CI: 1.05-3.53; p = 0.034) and OMD (HR 0.49; 95% CI: 0.29-0.81; p = 0.006) were significantly associated with PFS. ER-positive status (HR 0.65; 95% CI: 0.38-1.11; p = 0.115) and Ki-67 index (HR 1.01; 95% CI: 0.996-1.021; p = 0.178) met the threshold for inclusion in multivariate analysis. In the multivariate model, both OMD and G3 grade remained independently associated with PFS. High histological grade was confirmed as a significant negative prognostic factor (HR 2.40; 95% CI: 1.08-5.28; p = 0.030). Conclusions: Histological grade emerged as an independent prognostic factor, whereas ER status and Ki67 did not reach statistical significance. This finding highlights the prognostic relevance of traditional histopathological features in de novo HER2-positive MBC treated with TPH. High-grade tumors were associated with significantly shorter PFS, suggesting the need for intensified or alternative therapeutic strategies in this subgroup. While histopathology offers valuable prognostic insights, molecular profiling holds the potential to deliver a deeper biological understanding and enables more precise treatment stratification in this heterogeneous disease.

R. Levenson¹, E. Seibel², B. Wiafe-Addai³, F. Fereidouni⁴; ¹Dept. of Pathology and Laboratory Medicine, UC Davis Health, Sacramento, CA, ²Mechanical Engineering, University of Washington, Seattle, WA, ³Surgery, Peace and Love Hospital, Kumasi, GHANA, ⁴Pathology and Laboratory Medicine, Emory University, Atlanta, GA.

Fluorescence imitating brightfield imaging (FIBI) and related modes provide near-instantaneous slide-free histology. Benefits include greatly accelerated patient-lesion assessment in major clinical center, but also accessible diagnostics for lower- and middle-income countries. In addition, the technology can be an improvement over standard histology, as it achieves visualization of novel tissue features not readily assessed on standard slides. The approach used is termed FIBI (fluorescence imitating brightfield imaging), which features inexpensive and robust hardware, automated specimen scanning and forthcoming computer-aided diagnosis. This innovative, non-destructive technique employs affordable optics and sensors to image intact tissues within seconds to minutes. A previously published preliminary validation study demonstrated approximately 97% clinical concordance across diverse tumor types. Complementing FIBI, we are developing a sample management platform to stain and image core-needle biopsy specimens with minimal physical manipulation, preserving tissue integrity.While this set of features will be helpful in well-resourced medical centers, they are also well-suited to responding to patient care needs in lower resource settings. One example: lower- and middle-income countries (LMICs) face an urgent need for point-of-care breast cancer diagnosis and treatment planning. With no mammography screening available, many patients present with late-stage tumors that are typically evaluated using core-needle biopsies. However, it is not possible to obtain complete time-of-procedure diagnostic feed-back, as formalin-fixation, embedding, sectioning, and pathologist examination are typically involved, and the facilities required are scarce and unevenly distributed. Even when presenting with large lesions, patients often endure weeks to months of waiting before receiving a diagnosis and commencing appropriate treatment. FIBI can be implemented with automated specimen scanning and, soon, computer-aided diagnosis. A prototype system for needle biopsy staining and automated specimen scanning using FIBI slide-free surface imaging has been developed at UC Davis in conjunction with Emory University, and a version of this designed at the University of Washington has been deployed to the Peace & Love Hospital in Kumasi, Ghana. Images are captured within a few minutes after core-needle biopsy acquisition and have similar appearance to standard 20X H&E-stained slides. However, while the main histological features in FIBI derive from optical absorbance of superficial hematoxylin and eosin stains, there is information also being detected arising from the simultaneous fluorescence of tissue features such as elastin and collagen. This gives rise to images with a color gamut that goes beyond the pinks and blues usually visible in standard H&E-stained slides. In addition, because FIBI images thick specimens, some extended structures, such as blood vessels, are captured with much improved structural fidelity.

N. Thampy¹, K. Young-Zvandasara¹, C. M. Bacon², C. Chen³, N. Harris¹, M. Howe¹, A. Long¹, L. Mansfield¹, J. Ness¹, K. A. Wharton Jr⁴, S. Dance⁵, L. J. Inge³; ¹Cellular Pathology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UNITED KINGDOM, ²Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UNITED KINGDOM, ³Ventana Medical Systems, Roche Diagnostics Ltd, Tuscon, AZ, ⁴Oncology, Genetics and Pathology, Roche Diagnostics Ltd, Boston, MA, ⁵Medical Science Liaison Oncology, Roche Diagnostics Ltd, West Sussex, UNITED KINGDOM.

Background: Accurate detection of HER2 gene amplification via in situ hybridization (ISH) is critical for guiding targeted therapy use in patients with breast cancer. Traditionally, this involves manual quantification of the HER2-to-chromosome 17 (HER2/CHR17) signal ratio; however, this process is often time-consuming and may be complicated by factors such as chromosome 17 polysomy or intratumoral heterogeneity. The uPath HER2 Dual ISH image analysis algorithm is a tool for research use only, developed to assist medical laboratory scientists with determining HER2 gene status from images of formalin-fixed, paraffin-embedded (FFPE) neoplastic breast tissue. The algorithm was previously validated with samples stained using the VENTANA BenchMark ULTRA platform, but its performance across alternative staining platforms has not yet been evaluated. Methods: This study was designed to evaluate agreement between the BenchMark ULTRA and XT staining platforms, and between manual and algorithm-assisted methods for scoring across both platforms. In total, 120 advanced breast cancer FFPE samples with varying levels of HER2 amplification were selected for analysis (amplified [HER2/CHR17 ratio > 2.6], n = 50; non-amplified [HER2/CHR17 ratio < 1.4], n = 50; borderline amplified [HER2/CHR17 ratio ≥ 2.0 and ≤ 2.5], n = 10; borderline non-amplified [HER2/CHR17 ratio ≥ 1.5 and ≤ 1.9], n = 10). Tissue sections were prepared and stained using the VENTANA HER2 Dual ISH DNA probe cocktail using both the BenchMark ULTRA and XT platforms. Two trained medical laboratory scientists performed blinded manual quantification of HER2 ISH across all samples. These results were then checked by pathologists (n = 3). Following a washout period, these pathologists repeated the analysis using the algorithm. Results: High inter-platform agreement was observed with the algorithm across 118 evaluable samples, with an overall percent agreement (OPA) of 94.9% (95% confidence interval [CI], 89.3-97.6); positive percent agreement (PPA) and negative percent agreement (NPA) were 95.1% (95% CI, 86.5-98.3) and 94.7% (95% CI, 85.6-98.2), respectively. High agreement was observed between the algorithm and manual reads irrespective of the platform used for staining (Table 1). Perfect agreement was observed between manual reads across the two platforms. Conclusions: These data demonstrate that the uPath HER2 Dual ISH image analysis algorithm offers similar performance to manual scoring across samples stained using either the BenchMark ULTRA or XT platforms, and across samples with varying levels of HER2 amplification. With further validation, the algorithm may provide pathologists with a reliable adjunctive tool to support the diagnosis of patients with breast cancer.

L. Schwartzberg¹, T. Gillespie², E. Roeland³, T. Tyler⁴, R. Agarwal⁵, A. Alonzi⁶, T. Fralich⁷, P. Mudumby⁸, G. Aweh⁸, M. Fisher⁸, H. Rugo⁹; ¹William N. Pennington Cancer Institute, Renown Health, Reno, NV, ²Department of Hematology and Medical Oncology, Emory University School of Medicine, Winship Cancer Institute, Atlanta, GA, ³Division of Hematology and Medical Oncology, Oregon Health and Sciences University, Portland, OR, ⁴Desert Regional Medical Center, Comprehensive Cancer Center, Palm Springs, CA, ⁵Department of Medicine, Division of Hematology and Oncology, Vanderbilt University Medical Center, Vanderbilt-Ingram Cancer Center, Nashville, TN, ⁶Medical Affairs, Helsinn Healthcare, Lugano, SWITZERLAND, ⁷Medical Affairs, Helsinn Therapeutics, Inc., Iselin, NJ, ⁸Real-World Evidence, STATinMED, Dallas, TX, ⁹Department of Medical Oncology & Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte, CA.

Background: Antibody-drug conjugates (ADCs) are increasingly used to treat breast cancer (BC) and are often administered over prolonged periods. While nausea and vomiting (NV), including long-delayed nausea, are well-established side effects, limited real-world evidence exists evaluating antiemetic outcomes over extended treatment durations. This analysis evaluated 12-month real-world clinical and economic outcomes in U.S. patients with BC receiving ADCs, using national claims data. Outcomes were assessed for NCCN-guideline recommended antiemetic agents: NEPA (netupitant/palonosetron), distinguished by its prolonged NK1 receptor occupancy and extended half-life, and fos(aprepitant). Methods: A retrospective claims analysis using the STATinMED RWD Insights all-payer medical and pharmacy claims database evaluated patients with BC treated between January 1, 2019, and December 31, 2023. The index date was defined as the earliest claim for either NEPA or (fos)aprepitant. Eligible patients were ≥18 years with a BC diagnosis who received one of three ADCs—trastuzumab emtansine (T-DM1), trastuzumab deruxtecan (T-DXd), or sacituzumab govitecan (SG)—and maintained continuous medical and pharmacy benefits for 12 months before and after the index date. To minimize confounding, 1:1 propensity score matching was conducted to create balanced cohorts for NEPA vs fos(aprepitant) based on demographics and clinical variables including sex, geographic region, payer type, and comorbidity burden. Clinical outcomes were compared for NEPA vs (fos)aprepitant and included claims for nausea or vomiting or related complications (i.e., dehydration, IV fluid use, and/or electrolyte imbalance) occurring at least once during the 12-month evaluation period. Nausea occurring >72 h after the index date was also assessed. Outpatient hospital services (i.e., hospital-based care not involving admission or emergency treatment) and outpatient and emergency room costs were also determined for the two cohorts. NV-related utilization and costs were identified based on the presence of a NV diagnosis code in any position on the medical claim. Statistical analyses included descriptive statistics and hypothesis testing to evaluate differences between cohorts. Results: In the matched cohort analysis of 209 patients per group (n = 192 T-DM1, n = 154 T-DXd, and n = 72 SG of total population), NEPA had improved clinical and economic outcomes compared with (fos)aprepitant. During the 12-month post-index period, significantly fewer NEPA patients (82.3%) experienced nausea or vomiting or related clinical complications than (fos)aprepitant patients (90.4%; p=0.0154). Nausea rates >72 h were significantly lower for NEPA (27.8%) compared to (fos)aprepitant (40.2%; p=0.0073). Outpatient hospital services related to NV were also significantly lower with NEPA (43.0%) compared to (fos)aprepitant (69.4%; p<0.0001). The mean NV-related outpatient and emergency room cost for NEPA was $14,884, less than half the cost for (fos)aprepitant ($30,665; p<0.0001). While claims data offer valuable insights into real-world treatment patterns and outcomes, they have inherent limitations including potential coding inaccuracies, lack of clinical detail, and incomplete capture of patient-reported outcomes or uninsured care. Conclusion: These findings highlight clinical and economic benefits of NEPA-based antiemetic prophylaxis in patients with BC receiving ADCs. Given that patients often undergo prolonged ADC treatment, selecting an antiemetic regimen with sustained efficacy─such as NEPA in this database analysis─may be particularly important to minimize complications, lower healthcare utilization and cost, preserve quality of life, and support treatment continuity.

L. Visani¹, I. Ratosa², R. Bartsch³, B. Linderholm⁴, G. Griguolo⁵, C. Becherini¹, M. Valzano¹, V. Salvestrini¹, A. Starzer³, P. Kus⁶, M. Lambertini⁷, V. Guarneri⁵, L. Livi⁸, I. Meattini⁸; ¹Radiation Oncology & Breast Unit, Azienda Ospedaliero-Universitaria Careggi, Firenze, ITALY, ²Medical faculty and Division of Radiotherapy, University of Ljubljana and Institute of Oncology Ljubljana, Ljubljana, SLOVENIA, ³Clinical Research Unit, Division of Oncology, Department of Medicine I, Medical University of Vienna, Wien, AUSTRIA, ⁴Medical Oncology Unit, Department of Oncology, Sahlgrenska Academy and University Hospital, Göteborg, SWEDEN, ⁵Department of Surgery, Oncology and Gastroenterology, Division of Oncology 2, University of Padova and Istituto Oncologico Veneto IRCCS, Padova, ITALY, ⁶Department of Oncology, University Medical Centre Maribor, Maribor, SLOVENIA, ⁷Department of Internal Medicine and Medical Specialties (DiMI), School of Medicine, University of Genova, Genova, ITALY, ⁸Department of Experimental and Clinical Biomedical Sciences “M. Serio”, University of Florence, Firenze, ITALY.

Background. Trastuzumab deruxtecan (T-DXd) has emerged as the standard treatment for patients with metastatic HER2-positive (HER2+) breast cancer (BC) following disease progression on first-line therapy containing taxanes and trastuzumab. Results from DESTINY-Breast04 have extended the approval of T-DXd to include metastatic BC patients with HER2-low expressing tumours. Radiation therapy (RT) is an integral component of multimodal treatment in the metastatic setting. This retrospective study aims to evaluate the safety of the concurrent use of T-DXd and RT in a consecutive, multicentre international cohort. Material/Methods. A retrospective analysis was conducted on patients with metastatic HER2+ or HER2-low BC treated at six leading European institutions. Ablative RT was defined based on a biological dose threshold of a minimum of 50Gy EQD2(10) delivered in no more than 12 fractions, as per the European Society for Radiotherapy and Oncology (ESTRO) OligoCare study. The primary objective was to assess the association between RT administration and adverse events (AEs) greater than grade 2 (G2). In all cases, RT was administered within one month prior to cycle 1 or during systemic treatment, without any interruption of T-DXd. Results. Data from 147 consecutive patients were evaluated. Sixty-seven patients received RT immediately before or during T-DXd treatment, amounting to 71 concurrent RT treatments, while 80 patients did not receive RT. The median age was 53 years old (range 28-88), and the median follow-up from T-DXd initiation was 15 months (range 1-46). Most patients received T-DXd as fourth or beyond line of systemic therapy (52.4%, N=77/147). The median total RT dose was 44Gy (range 8-48), delivered over a median of 4 fractions (range 1-20). The median EQD2 dose was 82Gy (range 12-104), and the median BED was 98Gy (range 14-125). The central nervous system was the most frequently treated site (58.2%; N=39/67), followed by bone (31.3%; N=21/67). Thirty-six patients (53.7%) received RT with ablative intent, and 31 patients (46.3%) received palliative RT. The relationship between RT and the development of >G2 overall toxicity was not statistically significant (p=0.30), nor when considering acute toxicity >G2 (p=0.31) and late toxicity >G2 (p=0.59) separately. There was no significant association between EQD2 (<50Gy or ≥50Gy) and BED (G2 and any grade acute and late toxicity. The only factor associated with an increased risk of acute toxicity was age ≥50 years old (p=0.035). Grade 2 interstitial lung disease (ILD) or G2-3 pneumonitis were observed in 7 cases in the RT group (10.5%) and 7 cases in the no-RT group (8.8%). Only one case of radionecrosis was reported among the 39 patients treated with intracranial RT (median follow up of 11 months). Overall, 19 patients permanently discontinued T-DXd due to toxicity, 8 in the RT group (11.9%) and 11 in the no-RT group (13.8%). Conclusion. Our preliminary findings suggest that the combination of T-DXd and concurrent RT does not increase the risk of severe acute and late toxicity.

S. Sardesai¹, M. Ru², X. Ma³, C. Keane³, J. Wang³, M. Miranda⁴, X. Xu², C. Isaacs⁵; ¹Internal Medicine, Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, ²Oncology Outcomes Research, AstraZeneca, Gaithersburg, MD, ³Flatiron Health, Inc., New York, NY, ⁴Oncology Outcomes Research, AstraZeneca, Cambridge, UNITED KINGDOM, ⁵Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC.

Background: In 2022, the US FDA approved adjuvant olaparib for patients (pts) with germline pathogenic/likely pathogenic mutations in BRCA1 and/or BRCA2 (gBRCAm) and high-risk HER2-negative (HER2−) early breast cancer (eBC), based on significant survival improvements with olaparib vs placebo in OlympiA. In clinical practice, select pts with high-risk HER2− eBC may also receive CDK4/6 inhibitors (CDK4/6i) or immuno-oncology (IO) therapies; however, data are limited on treatment preference and sequencing in these pts. We describe real-world treatment patterns in US pts with gBRCAm HER2− eBC. Methods: Data from pts aged ≥18 years diagnosed with HER2− eBC (stage I-III) between January 1, 2021, and January 31, 2025, and with gBRCAm, were captured in the deidentified, electronic health record-derived Flatiron Health Research Database. Demographics, clinical characteristics, and treatment patterns were described across tumor subtypes (hormone receptor-positive [HR+] or triple-negative eBC [TNBC]). Pts with high-risk eBC were defined using criteria adapted from OlympiA (Tutt et al. NEJM 2021). Results: A total of 1954 pts with gBRCAm HER2− eBC were included (Table). Median age at diagnosis was 51 years among 1241 pts with HR+ eBC and 47 years among 713 pts with TNBC. Of 1010 pts with HR+ eBC who received adjuvant therapy, 217 (21%) received olaparib (including 19 pts who received olaparib before, 2 with, and 5 after CDK4/6i); 61 pts (6%) received CDK4/6i with endocrine therapy (ET) but without olaparib, 42 (4%) received IO without olaparib, and 282 (28%) received chemotherapy alone; 845 (84%) received ET, with or without other adjuvant therapies. Of 443 pts with TNBC who received adjuvant therapy, 162 (37%) received olaparib (93 received olaparib without IO; of 69 pts who received olaparib with IO, 18, notably, initiated olaparib before/concurrently with IO and 51 initiated olaparib after IO, including 50 within 27 weeks of initiating adjuvant IO); 196 (44%) pts received IO without olaparib and 82 (19%) received chemotherapy alone (including capecitabine in 8 pts). Among pts who received adjuvant therapy, 98/215 (46%) pts with high-risk HR+ eBC and 112/182 (62%) with high-risk TNBC received olaparib. Of 176 pts with TNBC without a pathological complete response (pCR) after neoadjuvant chemotherapy/IO, 90 (51%) did not receive olaparib. Among olaparib-treated pts, 119/217 (55%) with HR+ eBC and 50/162 (31%) with TNBC were not high risk. Conclusions: Real-world analysis showed that >40% of pts with gBRCAm, high-risk HER2− eBC did not receive adjuvant olaparib. Real-world olaparib use often did not align with restrictive criteria outlined in OlympiA, highlighting the need for comprehensive risk assessment to inform adjuvant treatment decisions in pts with gBRCAm HER2− eBC. Although prospective data is lacking, olaparib was frequently used concurrently with or after IO in pts with TNBC.

J. L. Meisel¹, T. Pham², C. Chen², A. Kris³, J. Roose⁴; ¹NA, Winship Canter Institute of Emory University, Atlanta, GA, ²Oncology Outcomes Research, AstraZeneca, Gaithersburg, MD, ³NA, Flatiron Health, Durham, NC, ⁴NA, Flatiron Health, New York, NY.

Background: Estrogen receptor alpha 1 (ESR1) mutations (m) are a significant driver of resistance to endocrine therapy (ET) in estrogen receptor-positive (ER+) advanced breast cancer (BC), leading to disease progression. Although the PADA-1 and SERENA-6 clinical studies highlighted the clinical relevance of monitoring for ESR1m emergence during first-line therapy (1L) and showed improvement in outcomes when therapy is changed upon detection, less is known about the real-world practice for patients with emergent ESR1m before progression and their outcomes. This study aims to characterize treatment patterns of patients whose tumors were tested for ESR1m during 1L and assess the impact of ESR1m on clinical outcomes, including real-world overall survival (rwOS) and real-world progression-free survival (rwPFS). Methods: This retrospective, observational cohort study used the US-based, deidentified Flatiron Health Research Database. Adult patients with a confirmed diagnosis of ER+/human epidermal growth factor receptor 2-negative (HER2-) metastatic BC from 1/1/2018 to 6/30/2024 were included. Treatment patterns were descriptively analyzed. rwOS and rwPFS were estimated for those with ESR1m emergence at first ESR1 test during 1L (time zero) using the Kaplan-Meier methodology and compared to those without ESR1 emergence at first ESR1 test using 1:1 propensity score matching on key covariates (time from 1L start to first ESR1 test result, ER expression level, presence of liver metastases, age, duration of prior aromatase inhibitor (AI) therapy, menopausal status). Results: This study included 8581 eligible patients, of whom 7772 (91%) initiated 1L therapy. Tumor ESR1m status was evaluated for 1335 (17%) during 1L, and 1086 were eligible for rwOS and rwPFS analyses. Treatment patterns in 1L were comparable between patients with (n=240) and without (n=1095) ESR1m emerging during 1L, with cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) + AI being the most common 1L treatment for patients with (140/240; 58%) and without (591/1095; 54%) ESR1m. CDK4/6i + fulvestrant was the second most common treatment for patients with (56/240; 23%) and without (248/1095; 23%) ESR1m. Patients not receiving 1L CDK4/6i + AI or CDK4/6i + fulvestrant received either ET monotherapy (9%), chemotherapy (3%), or other therapy (8%). Among patients who initiated 2L, those with an ESR1m detected during 1L compared to those without an ESR1m were more likely to receive 2L CDK4/6i + fulvestrant (49/202; 24% vs 93/573; 16%) or 2L elacestrant (29/202; 14% vs 1/573; 0.2%). Among those with an ESR1m detected during 1L (n = 240), median time to positive ESR1 test result was 18 months (mos) (IQR, 4-33) Median time from ESR1m detection during 1L to progression was 5.9 months.Eligible patients with an ESR1m detected on their earliest ESR1 test during 1L (n = 105) had shorter median rwPFS and median rwOS compared with those without an ESR1m (n = 981, rwPFS 7.7 mos [95% CI: 5.8-11.4] vs. 15.3 mos [95% CI: 14.0-16.8]) and (rwOS 32.2 mos [95% CI: 21.1-Not Reached (NR)] vs 45.6 mos [95% CI: 41.7-54.0]). After propensity score matching, both median rwPFS (7.7 mos [95% CI: 5.7-11.4] vs 13.6 mos [95% CI: 9.9-16.5]; hazard ratio [HR] 0.68 [95% CI: 0.48-0.96]) and median rwOS (32.2 mos [95% CI: 21.1-NR] vs NR [95% CI: 35.4-NR], HR: 0.58 [95% CI: 0.36-0.95]) were shorter in patients with an ESR1m detected during 1L. Conclusion: Patients with metastatic BC whose tumors were found to harbor an ESR1m during 1L had worse clinical outcomes than those who did not have an ESR1m. These findings highlight the potential clinical benefit of surveillance for ESR1m during 1L, and the need for treatment options that delay progression and improve clinical outcomes for patients with emerging ESR1-mutated, ER+ breast cancer.

A. Alexander¹, M. Kai¹, K. A. Abou-Hussein², S. Ali³, C. Anderson⁴, S. W. Bahadur⁵, Y. C. Cheng⁶, N. T. Ueno⁷, X. Wang⁸, A. Lucci⁹, W. A. Woodward¹⁰, S. Saleem¹¹, MDACC Inflammatory Breast Cancer Team; ¹Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, ²Hematology and Oncology, Cooper MD Anderson Cancer Center, Camden, NJ, ³Breast Medical Oncology, Scripps Health, La Jolla, CA, ⁴Breast Radiation Oncology, Baptist MD Anderson Cancer Center, Houston, TX, ⁵Breast Medical Oncology, Mayo Clinic Cancer Centet, Phoenix, AZ, ⁶Medical Oncology, Medical College of Wisconsin, Milwaukee, WI, ⁷Medicine, University of Hawaii Cancer Center, Honolulu, HI, ⁸Surgical Oncology, Rush MD Anderson Cancer Center, Chicago, IL, ⁹Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, ¹⁰Breast Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, ¹¹Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Sugar Land, TX.

IBC Clear: A decentralized multi-center MRD Registry for Inflammatory Breast CancerInflammatory breast cancer is an aggressive subtype of breast cancer with distinct clinical phenotypes, including early recurrence post-tri-modal care (neoadjuvant systemic therapy, surgery, adjuvant radiation). Preliminary data from MDACC have shown a high rate of baseline and serial MRD positivity in IBC patients (35-40% at 6-12 months post-surgery), suggesting that newly diagnosed IBC is an ideal population to test MRD as a standard of care and design adjuvant interventional trials. However, to date, our understanding of the optimal monitoring cadence and interventions following MRD positivity remains limited. IBC Clear is a decentralized protocol developed to collect real-world data from patients treated amongst our IBC Connect network of 19 US-based and three international institutions (7 of whom have expressed interest in participating). Patients who have had, or plan to have Signatera® ordered at the post-chemo/pre-surgery timepoint can self-enroll from the community by emailing IBCClear@mdanderson.org for information on the consent process. Study DesignEligibility criteria include English-speaking patients > 18 years of age with a clinical diagnosis of IBC, with Signatera testing ordered or planned. The post-chemo/pre-surgery timepoint is the only study-mandated timepoint; however, any additional serial testing conducted before or after this timepoint will also be collected. Patients who have at least one Signatera test ordered and plan to have a pre-surgery/post-chemo collection as standard of care will be enrolled in a central REDCap database. Physicians enrolling patients may act on the results according to their clinical judgment, including imaging assessments and treatment changes. These interventions will be captured in the database. An electronic EORTC QLQ C30 survey will also be administered prior to and after receiving Signatera results to gather information about the impact of testing on the patient’s quality of life. A total of 200 patients from all sites will be enrolled over a period of two years. Patients will be followed remotely for up to 2 years from the first Signatera test or until clinical recurrence, whichever comes first.EndpointsData collected will include the feasibility of decentralized data collection studies, as well as Signatera and recurrence information. The goals are to gather real-world data regarding the association of MRD positivity with pathologic response in IBC, patient-reported QOL for worry about recurrence, median lead time between the first MRD-positive result and clinical recurrence, and, if possible, whether the adjuvant therapies decrease the amount of MRD in IBC patients (pending optional longitudinal testing).Status of the study: The study was activated in June 2025. As of abstract submission, 2 patients have been enrolled at the lead site. Collaborating sites are being added. Sponsor: The University of Texas MD Anderson Cancer Center Clinicaltrials.gov Accession number: NCT06966050

A. Roy¹, Y. Gokun², B. Slover², N. Lopetegui-Lia¹, D. Quiroga¹, G. Bader¹, M. Cherian¹, A. Davenport¹, K. Johnson¹, S. Sardesai¹, R. Wesolowski¹, S. Myers³, E. Burke³, M. Gatti-Mays¹, N. Williams¹, D. Stover¹; ¹Department of Medicine, The Ohio State University, Columbus, OH, ²Center for Biostatistics, The Ohio State University, Columbus, OH, ³Department of Surgery, The Ohio State University, Columbus, OH.

Background: Invasive lobular carcinoma (ILC) accounts for 10-15% of breast cancer (BC) cases and is predominantly hormone receptor-positive (HR+) and HER2-negative (HER2-). Although existing data indicates that ILC is less responsive to chemotherapy (CT) than invasive ductal carcinomas, the benefit of adjuvant CT in early-stage (ES) ILC is incompletely characterized. Further, the utility of the Oncotype DX Recurrence Score (RS), which has been used to predict response to CT in HR+/HER2- BC, has been debated for ILC. To address these issues, we studied the role of adjuvant CT on overall survival (OS) and by RS categories in ES ILC. Methodology: We queried the National Cancer Database for patients (pts) with ES HR+ HER2- ILC who underwent upfront surgical resection between 2010-2021. Pts were categorized to two cohorts based on receipt of adjuvant CT (CT+ and CT-). Subgroup analyses were performed based on RS score categories: low (L) 0-15, intermediate (I) 16-25, high (H) ≥26). Kaplan-Meier curves and log-rank tests determined OS between cohorts. Multivariate Cox proportional hazards models assessed OS, adjusting for potential confounders including age, race, stage, grade, and treatment variables. Results: Of the 162,430 ILC pts identified, 79.6% received adjuvant CT. The CT+ cohort were more likely to be younger pts (median age, IQR: 65 (55, 75) vs 66 (56, 72) years), have fewer comorbidities (Charlson-Deyo score (CDS) 0: 82.5 vs 82.3%, CDS 1: 13.1 vs 12.6%), intermediate grade disease (64.1 vs 62.2%), tumors <2 cm (67.1 vs 50.7%), clinically node negative disease (92.0 vs 77.7%), and receive radiation (63.5 vs 52.3%), and hormonal therapy (98.4 vs 51.4%), (all p<0.001). In the CT+ cohort, more pts had RS L (20.2 vs 8.9%), I (17.1 vs 7.5%), H (3.1 vs 1.7%) compared to CT-cohort (p<0.001). CT receipt conferred higher 5-year and 10-year OS. This survival benefit with adjuvant CT was observed among all RS groups with the highest benefit observed in H RS group (10Y OS: 84.5 vs 63.9%, p<0.001) (Table 1). In multivariate analysis adjusting for relevant confounders, receipt of adjuvant CT was associated with decreased morality in the overall ILC cohort (Hazard ratio (HR), 95% CI: 0.79, 0.76-0.83, p<0.001) and the RS subgroups, though not statistically significant in L RS group (HR, 95% CI: L – 0.77, 0.59 – 1.01, p= 0.06; I – 0.78, 0.62 – 0.98, p= 0.04; H – 0.67, 0.50 – 0.89, p= 0.006). Conclusion: In this study, adjuvant CT was associated with improved OS in ILC pts with RS> 15. These data support use of RS for CT decision-making in appropriate candidates. Further investigations are needed to identify ILC pts who would benefit the most from adjuvant CT.

A. Rodríguez-Hernández¹, J. Quintanilla², R. Graf², A. Schrock², A. Gasco², B. Bychkovsky¹, R. Kitadai¹, S. Morganti¹, D. Abravanel¹, S. Tolaney¹, J. Garber¹, R. Jeselsohn¹, N. Lin¹, F. Lynce¹; ¹Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, ²Foundation Medicine, Foundation Medicine, Boston, MA.

Background: PARPi are used to treat MBC, particularly in pts with genomic alterations (GA) in BRCA1/2 by targeting homologous recombination deficiency (HRD). This study explored clinical and genomic factors associated with PARPi sensitivity in a real-world MBC cohort. Methods: This retrospective study included 290 pts with MBC who had genomic testing via FoundationOne/FoundationOne CDx tissue comprehensive genomic profiling (CGP) and prior to treatment with a PARPi. Clinical data were sourced from the US-wide de-identified Flatiron Health-Foundation Medicine clinic genomic database, including ~800 sites across ~280 US cancer clinics (Jan 2011-Dec 2024). HRD alterations (alts) were defined as mutations, homozygous copy loss, or structural rearrangements in any of the following genes: BRCA1/2, ATM, ATR, ATRX, BAP1, BARD1, BRIP1, CHEK1/2, CDK12, FANCA, FANCL, MRE11, RAD51B/C/D, RAD54L or PALB2. HRD signature (HRDsig) status, which is offered as a laboratory professional service, was calculated using genome-wide copy number features, with scores from 0 to 1 and a predefined cutoff of 0.7 to call HRDsig (+). BRCA1/2 germline status was inferred using a validated somatic-germline-zygosity algorithm. Time to next treatment or death (TTNT) on PARPi was analyzed using Cox models adjusted for clinical variables. Results: Among 290 pts, most were female (96.6%, n=280), with a median age of 57 years at PARPi initiation. Of these, 186 (64.1%) had hormone receptor-positive (HR+) disease and 104 (35.9%) had HR- disease. In total, 21 had HER2+ tumors (12 HR+, 9 HR-). PARPi was given +/- endocrine therapy in 236 pts (81.4%) and in combination with other therapies in 54 (18.6%). PARPi was given in 1L (14.1%), 2L (26.9%), 3L (19.3%), and ≥4L (39.7%). Tumors from 199 patients (59.2%) were HRDsig (+): 120 (60.3%) HR+ and 79 (39.7%) HR−. Overall, 237 pts (81.7%) harbored ≥1GA (mutation, homozygous copy loss, or rearrangement) in BRCA1 (n=90), BRCA2 (n=130), or PALB2 (n=19). Nineteen pts had BRCAloss (8 in BRCA1 and 11 in BRCA2). In pre-PARPi CGP samples, HR+ tumors most frequently harbored BRCA2 (52.7%), TP53 (32.8%), BRCA1 (21.0%), while HR- tumors showed higher rates of TP53 (85.6%), BRCA1 (49.0%), BRCA2 (30.8%), and PALB2 (4.8%). Among pts with HR+ disease, those with a BRCAloss vs other BRCA GA detected prior to PARPi exposure had more favorable TTNT (median 15.2 vs. 8.5 months HR:0.40; p=0.012). No differences in TTNT were observed by BRCA1/2 mutation origin (germline (g) vs somatic (s)), type (truncating vs missense), or location (Table 1). Conclusions: Response to PARPi varied across different GA. Among pts with HR+ MBC, those with BRCAloss appeared to derive the greatest benefit. These findings highlight the potential utility of CGP in guiding PARPi treatment decisions.

S. Yadav¹, Q. Li², Z. Tan³, K. E. Mishkin⁴, J. F. Hayes⁵, X. Xu², F. J. Couch¹; ¹Department of Oncology, Mayo Clinic, Rochester, MN, ²Oncology Outcomes Research, AstraZeneca, Gaithersburg, MD, ³Oncology Outcomes Research, AstraZeneca, Mississauga, ON, CANADA, ⁴Oncology Outcomes Research, Merck & Co., Inc., Rahway, NJ, ⁵US Medical Affairs Oncology, AstraZeneca, Gaithersburg, MD.

Background: Clinical benefit with PARP inhibitors (PARPi) has been demonstrated in patients (pts) with HER2-negative (HER2−) metastatic breast cancer (mBC) and germline or tumor mutations in BRCA1 or BRCA2 (g/tBRCAm). Understanding real-world PARPi use and its impact on clinical outcomes may improve the treatment of pts with BRCAm HER2− mBC. Methods: This retrospective study captured data from US pts aged ≥18 years diagnosed with HER2− mBC from January 12, 2018, to March 31, 2024, in the deidentified electronic health record-derived Flatiron Health Research Database. PARPi use and outcomes were described by tumor subtype (hormone receptor-positive [HR+]/HER2− mBC or triple-negative mBC [mTNBC]), g/tBRCA status, disease stage at diagnosis (de novo or recurrent), line of therapy (LoT), and prior treatments. Real-world overall survival (rwOS) by PARPi use was estimated using the Kaplan-Meier method. Results: Of 848 pts with gBRCAm mBC, 352 (42%) received PARPi (Table), with consistent PARPi initiation rates of 42%-48% from 2018-2022. PARPi was initiated in 223/566 (39%) pts with gBRCAm HR+/HER2− mBC, 125/275 (45%) pts with gBRCAm mTNBC, and 4/7 (57%) pts with unknown tumor subtype. Among 304 pts with gBRCAm who had received ≥3 LoT by the end of follow-up, 93/225 (41%) pts with HR+/HER2− mBC and 18/78 (23%) pts with mTNBC received PARPi in the third LoT or later (3L+); 50/103 (49%) pts with de novo mBC and 54/184 (29%) pts with recurrent mBC received PARPi in 3L+. PARPi was also initiated in 13/231 (6%) pts with gBRCA variants of uncertain significance (VUS) and 176/662 (27%) pts with tBRCAm and non-gBRCAm/unknown gBRCAm status. Among 539/1573 (34%) pts with g/tBRCAm who received PARPi, 167 had not received prior chemotherapy in any setting; 40 of these pts (39 with HR+/HER2− mBC and 1 with mTNBC) received PARPi in 3L+. With a median follow-up of 17.0 months from initiation of 1L therapy, median rwOS was numerically longer among pts with gBRCAm who received PARPi versus pts who did not (HR+/HER2− mBC: 39.3 months [95% CI: 35.5-46.8], n=208 vs 24.2 months [95% CI: 21.4-33.0], n=259; mTNBC: 27.6 months [95% CI: 18.0-41.7], n=119 vs 16.9 months [95% CI: 14.5-31.9], n=81). Among pts with tBRCAm who were negative for gBRCAm, median rwOS was numerically longer in pts who received PARPi versus pts who did not. Conclusions: Pts with HR+/HER2− mBC had slightly lower rates of PARPi use, and received PARPi later, than pts with mTNBC. Although improved efficacy with PARPi use in earlier LoT has been demonstrated, many pts first received PARPi in 3L+, suggesting unmet potential to ensure timely testing and optimize treatment. Although immortal time bias and other factors should be considered, rwOS was numerically longer in pts with BRCAm HR+/HER2− mBC and with BRCAm mTNBC who initiated PARPi versus pts who did not. Further research into PARPi use and survival trends in pts with BRCAm and/or other actionable biomarkers in mBC is needed.

A. de Nonneville¹, D. Loirat², J. Ribeiro³, S. Becourt⁴, M. Benderra⁵, N. Benard⁶, M. Campone⁷, F. Dalenc⁸, O. Derbel⁹, I. Desmoulins¹⁰, A. Deleuze¹¹, G. Emile¹², A. Goncalves¹, J. Grenier¹³, W. Jacot¹⁴, C. Liautard⁶, L. Mansi¹⁵, M. A. Mouret Reynier¹⁶, C. Perkins⁶, B. Pistilli³, J. P. Spano¹⁷, A. Vasseur¹⁸, F. Penault Llorca¹⁹, O. Tredan²⁰; ¹Medical Oncology, Aix-Marseille Univ, CNRS, INSERM, Institut Paoli-Calmettes, CRCM, Marseille, FRANCE, ²Medical Oncology, Institut Curie- Institut of Women’s Cancers, Paris, FRANCE, ³Breast Unit, Medical Oncology Department, Gustave Roussy Cancer Campus, Villejuif, FRANCE, ⁴Medical Oncology, Centre Oscar Lambret, Lille, FRANCE, ⁵Department of Medical Oncology, Institut Universitaire de Cancérologie, Sorbonne University, AP-HP, Tenon Hospital, Paris, FRANCE, ⁶Medical affairs, MSD France, Puteaux, FRANCE, ⁷Medical Oncology, Institut de Cancérologie de l’Ouest, Saint Herblain, FRANCE, ⁸Medical Oncology, Oncopole Claudus Regaud, Toulouse, FRANCE, ⁹Medical Oncology, Hopital privé Jean Mermoz, Puteaux, FRANCE, ¹⁰Medical Oncology, Centre Georges-François Leclerc, Dijon, FRANCE, ¹¹Medical Oncology, Centre Eugene Marquis, Rennes, FRANCE, ¹²Medical Oncology, François Baclesse Comprehensive Cancer Center, Caen, FRANCE, ¹³Medical Oncology, Institut Sainte Catherine, Avignon, FRANCE, ¹⁴Medical Oncology, Institut du Cancer de Montpellier, Montpellier University, INSERM U1194, Montpellier, FRANCE, ¹⁵Medical Oncology, CHRU Jean Minjoz, Besancon, FRANCE, ¹⁶Medical Oncology, Centre Jean Perrin, Clermont, FRANCE, ¹⁷Medical Oncology, Pitié Salpêtrière AP-HP, Sorbonne Université, INSERM U 1136,, Paris, FRANCE, ¹⁸Medical Oncology, Institut Curie, Saint-Cloud, FRANCE, ¹⁹Pathology, Centre Jean Perrin, Université Clermont Auvergne, INSERM, U1240 Imagerie Moléculaire et Stratégies Théranostiques, Clermont Ferrand, FRANCE, ²⁰Medical Oncology, Centre Leon Berard, Cancer Research Center of Lyon (UMR Inserm 1052 – CNRS 5286), Lyon, FRANCE.

Background: Since the KEYNOTE-522 trial demonstrated improved pathological response and survival outcomes, pembrolizumab in combination with neoadjuvant chemotherapy, followed by adjuvant administration, is the current standard of care for stage II-III triple-negative breast cancer (eTNBC). Objective: This prospective national observational cohort analysis aims to describe real-world data from high-risk eTNBC patients treated with this schema through the French KN522 Early Access Program (EAP) from April 13, 2022, to November 20, 2024. Methods: Eligible patients were adults with confirmed stage II-III TNBC, including ER 1-9% according to French guidelines. Data were collected via physician-completed EAP forms and patient-reported EORTC QLQ-C30 questionnaires. Clinical and safety data were recorded until the EAP concluded or the end of the treatment. Results: A total of 7,687 patients were enrolled during the 31-month EAP across 427 healthcare centers and by 1,259 physicians. Participating centers included comprehensive cancer centers (34%), private clinics (34.1%), and public hospitals (31.8%). Median age of patients was 52 years (range 19-92 years) including 21.8% >65 years old and mean BMI was 26.3 kg/m² (IQR 22.2 – 29.4). 3002 (39,1%) patients had stage III disease, and 87.5% had an ECOG-PS of 0. Pembrolizumab was administered at the planned dose of 200 mg every three weeks for nearly all patients and 96.1% planned the chemotherapy regimen used in KN522 (carboplatin/paclitaxel -anthracycline/cyclophosphamide). A total of 1105 patients (14.4%) have temporary interrupted pembrolizumab treatment, predominantly during the neoadjuvant phase (74.3%), with 38.1% related to immune-mediated adverse events. The median duration of this interruption was 13 days. 1240 patients (16%) have permanently discontinued pembrolizumab with the main cause being suspected immune-related toxicity (49.1%). The second reported reason for permanent discontinuation was physician decision related to the pathological response (19.3%), whether it was complete (6.3%) or not (13%). The breast-conserving surgery rate was 63,8%, with a median interval of 28 days between the completion of neoadjuvant therapy and surgery. The overall pathological complete response (pCR) rate was 71.6%. For patients who experienced treatment interruption due to immune toxicity (n=737), the pCR rate was 71.2% and was 73.3% for patients younger than 30 years old (n=45). Additional systemic treatments were received by 8.8% of patients in the adjuvant phase (with a higher incidence for patients with residual disease). In most cases, it was chemotherapy, but PARPi and endocrine therapies were also reported. Quality of life data, assessed via the QLQ-C30, showed stable global health scores (mean score of 85.3 at neoadjuvant Cycle one (n=423) vs. 81.3 at adjuvant Cycle nine (n=40)). Pharmacovigilance reported a total of 417 serious treatment-related cases, including eight deaths. Conclusions: Thanks to the substantial participation of physicians and centers across France, FR-POP represents one of the largest real-world cohorts collecting relevant efficacy and safety data on KN522 regimen in clinical practice. With an observed pCR rate exceeding 70% despite the high proportion of stage III tumors, and in a non-selected and older population, these findings clearly point out the efficacy of this treatment strategy and the external validity of KN522 results. However, underreporting of adverse events and the absence of follow up after the end of treatment remain potential limitations of EAP-derived safety data and tolerance of this regimen should continue to be closely monitored.

D. Rodin¹, R. Sutradhar¹, E. Hahn¹, K. Jerzak¹, L. Nguyen², S. Trebinjac³, L. Laszat³, E. Rakovitch³; ¹Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, CANADA, ²Institute for Clinical Evaluative Sciences, Sunnybrook Health Sciences Centre, Toronto, ON, CANADA, ³Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, ON, CANADA.

PurposeTo determine the impact of adjuvant endocrine therapy (ET) among older women diagnosed with hormone positive (HR+), early-stage breast cancer (EBC) on the risks of recurrence and death, and on services utilization. Methods: We identified a population-based cohort of individuals >65 years with T1N0 HR+EBC, treated with breast-conserving surgery (BCS), with or without breast radiotherapy (RT), from Jan 2012- Aug 2021, and followed until December 2023. Exposure to ET was calculated for the 2-year interval following diagnosis, with ET adherence defined as ET use for >65% of the interval, with 1:1 matching performed for cases <65% adherent and those without ET exposure. We calculated the cumulative incidence of ipsilateral local recurrence (LR), contralateral breast cancer (CBC), and breast cancer mortality, adjusting for competing risk of death and stratified by receipt of RT. A difference-in-differences analysis with a Poisson regression was used to compare health service utilization between cases and controls. Results The study cohort included 3486 individuals (median age 71 years, 2,796 received RT); with 1162 in each group (>65% adherent, <65% adherent, and no ET). Among individuals who received RT, >65% adherence to ET was associated with a small absolute reduction in the 10-year cumulative risk of LR compared to no ET (>65% ET: 0.2% (95%CI: 0.05, 0.84); no ET: 3.4% (95%CI: 1.75, 5.93; p=.01)). There was no difference in 10-year risks of CBC or breast cancer mortality. Among individuals who did not receive RT, >65% adherence to ET was associated with a greater reduction in 10-year LR risk (1.8% (95% CI: 0.33, 6.13) vs 7.0% (95%CI: 3.6, 12.0; p=.04)) and a small reduction in breast cancer mortality (0% vs 3.3% (95% CI: 1.2, 7.3; p=0.03)), compared to those who did not receive ET. Health care utilization was significantly increased with ET use and was greatest for individuals >65% adherent, with significantly more diagnostic imaging tests, primary care, and specialist physician visits compared to those who did not receive ET (Table). Individuals <65% adherent had a smaller absolute benefit from ET, but similarly high health service utilization.. Conclusions For older individuals with stage T1N0 HR+EBC, adjuvant ET is associated with a significant increase in health care utilization. For individuals treated with BCS+RT, ET was associated with a small absolute reduction in LR but no difference in CBC or BC mortality, suggesting that the burden of ET may outweigh the benefit in this population.

H. Abdallah¹, O. Ayodele², A. Ghose³, Y. Owoseni², A. Maniam⁴, B. Baraka⁵, S. Horne⁶, A. Nazir⁶, L. Mooney⁷, F. Nazeer⁸, N. Atsumi⁴, L. McAvan⁹, M. Abraham¹⁰, E. Bean¹¹, D. Morgan¹², G. Langford¹², E. Morris¹³, R. Muhammad¹⁴, E. Daniels¹⁵, R. Pravinkumar¹⁶, S. Mohammed¹⁷, S. Raza¹⁸, C. Blair¹⁹, R. Khan²⁰, M. Tsalic⁶, R. Kussaibati⁶, R. Douglas⁷, K. Panagiotis²¹, S. Waters¹², J. Smith¹¹, E. Papadimitraki¹³, C. Michie¹⁶, C. Wilson²⁰, A. Konstantis¹⁴; ¹Oncology Department, Cambridge Clinical Research Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, UNITED KINGDOM, ²Oncology Department, University Hospitals of Leicester NHS Trust, Leicester, UNITED KINGDOM, ³Oncology Department, Barts Cancer Centre, Barts Health NHS Trust, London, UNITED KINGDOM, ⁴Oncology Department, Portsmouth Hospitals University NHS Trust, Portsmouth, UNITED KINGDOM, ⁵Oncology Department, Nottingham University Hospitals NHS Trust, Nottingham, UNITED KINGDOM, ⁶Oncology Department, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UNITED KINGDOM, ⁷Oncology Department, Northern Ireland Cancer Centre, Belfast Health and Social Care Trust, Belfast, UNITED KINGDOM, ⁸Oncology Department, Royal Surrey Cancer Centre, Royal Surrey NHS Foundation Trust, Surrey, UNITED KINGDOM, ⁹Oncology Department, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, UNITED KINGDOM, ¹⁰Oncology Department, Dorset Cancer Centre, University Hospitals Dorset NHS Foundation Trust, Poole, UNITED KINGDOM, ¹¹Oncology Department, Northern Centre for Cancer Care, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle, UNITED KINGDOM, ¹²Oncology Department, Velindre Cancer Centre, Velindre University NHS Trust, Cardiff, UNITED KINGDOM, ¹³Oncology Department, University College London Hospitals NHS Foundation Trust, London, UNITED KINGDOM, ¹⁴Oncology Department, Princess Alexandra Hospital NHS Trust, Harlow, UNITED KINGDOM, ¹⁵Oncology Department, Dyson Cancer Centre, Royal United Hospitals Bath NHS Foundation Trust, Bath, UNITED KINGDOM, ¹⁶Oncology Department, Edinburgh Cancer Centre, Edinburgh, UNITED KINGDOM, ¹⁷Oncology Department, Great Western Hospitals NHS Foundation Trust, Swindon, UNITED KINGDOM, ¹⁸Oncology Department, Hull University Teaching Hospitals NHS Trust, Cottingham, UNITED KINGDOM, ¹⁹Oncology Department, University Hospitals of Bristol and Weston NHS Trust, Bristol, UNITED KINGDOM, ²⁰Oncology Department, The Christie NHS Foundation Trust, Manchester, UNITED KINGDOM, ²¹Oncology Department, Frimley Health NHS Foundation Trust, Camberley, UNITED KINGDOM.

Background Adjuvant Abemaciclib (AA) combined with endocrine therapy (ET) significantly improves invasive disease-free survival (IDFS) in patients with hormone receptor-positive (HR+), HER2-negative (HER2 -), node-positive early breast cancer (EBC), as demonstrated in the monarchE trial. However, only 15.6% of patients in monarchE were aged ≥65 and no dedicated geriatric safety analysis was performed. Managing older adults with EBC is complex due to comorbidities, reduced physiological reserve and polypharmacy. There is limited real-world evidence on the safety and tolerability of AA in this population. Methods The CONCISE study is a retrospective, multicentre audit of UK practice across 21 centres, including patients treated with AA from July 2022 to April 2025. This analysis focuses on patients aged ≥65 years. Data were collected using the Ledidi platform and analysed using descriptive statistics in Jamovi. Key outcomes include treatment duration, dose modifications and adverse events (AEs), stratified by two subgroups: Cohort 1 (age 65-75) and Cohort 2 (>75). Group comparisons were performed using chi-squared and t-test. Results Of 1,026 patients, 215 (21%) were aged ≥65: 152 in Cohort 1 (median age 69) and 63 in Cohort 2 (median age 78). Most were female (96.3%) and Caucasian (88.4%). Stage II disease was most common (56.7%), with grade 2 tumours (57.8%) and nodal involvement (72.8%). Chemotherapy use differed by age: in Cohort 1, 68% received adjuvant chemotherapy and 11% neoadjuvant chemotherapy; in Cohort 2, only 31% received adjuvant chemotherapy and one patient had neoadjuvant chemotherapy.Median AA duration was 12.6 months in Cohort 1 vs. 8.3 months in Cohort 2 (p=0.028). Discontinuation of the treatment due to toxicity was significantly more common in Cohort 2 (79%) than in Cohort 1 (49%) [p=0.002]. Treatment completion (24 months) was achieved in 47% (Cohort 1) and 21% (Cohort 2). At data cut-off, 53% and 40% of patients remained on treatment in Cohorts 1 and 2, respectively. Disease progression occurred in 4% (Cohort 1) and 0% (Cohort 2).One-level dose reductions were required in 70% (Cohort 1) and 76% (Cohort 2) [p=0.29], while further reductions were needed in 34% and 38% [p=0.55], respectively. The most frequent AEs were diarrhoea (75% vs. 71.4%), anaemia (40% in both), and neutropenia (34.2% vs. 30.2%), with grade ≥2 rates comparable between groups.

Conclusion In this large UK real-world cohort, older adults with high-risk EBC experienced similar AE profiles to younger counterparts, but with numerically higher discontinuation rates, particularly in those aged >75. Dose reductions were common across both age groups. These findings underscore the importance of careful patient selection, supportive care, and geriatric assessment when offering AA in routine clinical practice.

D. Shankarraman¹, G. Sivaramalingam², N. Govindarajan³, S. Radhakrishna¹; ¹Breast Surgery, Chennai Breast Centre, Chennai, INDIA, ²Radiology – Breast Imaging and Interventions, Chennai Breast Centre, Chennai, INDIA, ³Pathology, Chennai Breast Centre, Chennai, INDIA.

Bridging Diagnostic Gaps in LMICs: Real-World Functionality of a One-Stop Breast Centre in South IndiaBackgroundIn low- and middle-income countries (LMICs), fragmented diagnostic pathways often result in delayed breast cancer diagnosis and treatment. Patients are typically referred across departments (surgery, radiology, pathology), leading to multiple visits and potential loss to follow-up. The One-Stop Breast Clinic (OSBC) model, which integrates clinical evaluation, imaging, and biopsy into a single coordinated visit, aims to streamline this process. We present real-world data from a high-volume OSBC in South India to evaluate its diagnostic performance and workflow efficiency.ObjectiveTo assess the feasibility, diagnostic accuracy, and operational efficiency of the OSBC model in a private healthcare setting in India.MethodsThis retrospective audit included all female patients seen at Chennai Breast Centre from January 1 to December 31, 2024. Data were collected on patient demographics, imaging origin and quality, need for repeat evaluations, biopsy results, and diagnostic timelines. New symptomatic patients and follow-up visits were analyzed separately. Key outcome measures included the rate of repeat imaging/biopsy, time to biopsy, and time to treatment planning.ResultsAmong 12,156 patients, 2,777 were new symptomatic cases; 9,379 were follow-ups. New patients ranged in age from 12–93 years (mean: 47.5); Final diagnosis (new patients): Benign: 2,126 (76.5%), Malignant: 627 (22.6%)- Imaging origin: 1,158 (41.7%) had primary imaging at CBC; 1,619 (58.3%) presented with external scans- Repeat imaging required: 1,450 (52.2%), including 550 mammograms and 935 ultrasounds- Biopsies performed: 674 US-guided core biopsies, 2 punch, 8 stereotactic- MRI additionally performed in 70 patientsOf the 495 patients biopsied after repeat imaging, 384 had not been previously advised biopsy externally, suggesting significant diagnostic upgrades. Among 479 patients with prior external biopsies, 120 required a repeat biopsy; of these, 75 (62.5%) were malignant and 45 (37.5%) benign. This highlights a potential for missed malignancies with suboptimal external evaluations and emphasizes the critical need for quality-controlled, structured diagnostic workflows like the OSBC model. Workflow EfficiencyMedian time from patient entry to completion of history, clinical exam, imaging, and biopsy was 125 minutes. Biopsy reports were available within 72 hours. Unlike multispecialty hospitals that require multiple visits for triple assessment, the OSBC model completed this in a single session.Integrated Pathway– Visit 1: Triple assessment and biopsy- Visit 2: Biopsy review; staging and baseline workup initiated for malignancies- Visit 3: Treatment decision finalized with complete reports- Visit 4: Preoperative documentation- Visit 5: Daycare surgeryThis model particularly benefits patients traveling long distances. Staging workup and general health evaluations are performed while awaiting pathology results, ensuring that treatment planning occurs within 2–3 visits. The approach enhances patient compliance, reduces dropouts, and improves system-level efficiency.ConclusionThe OSBC model provides a practical, scalable solution to reduce diagnostic delays in LMICs. In this high-volume South Indian setting, triple assessment was achieved in <2 hours and definitive treatment planning within 3 visits. The model minimizes attrition, improves diagnostic accuracy, and optimizes patient flow. Expansion of such integrated breast care centers may be key to strengthening cancer care infrastructure in resource-limited settings.KeywordsOne-stop breast clinic, LMIC, breast cancer, triple assessment, diagnostic delay, India, integrated care, real-world evidence

J. Liu¹, G. Gong¹, S. Pandya², J. Xie³, J. Parikh³, N. Fischbach⁴, P. Kunz⁴, L. Pusztai¹, M. Lustberg¹; ¹Yale Cancer Center, Yale School of Medicine, New Haven, CT, ²Department of Laboratory Medicine, Yale School of Medicine, New Haven, CT, ³Yale College, Yale University, New Haven, CT, ⁴Department of Medicine, Division of Medical Oncology, Yale School of Medicine, New Haven, CT.

Background: Significant enrollment gaps persist in breast cancer clinical trials, particularly among patients with high-risk hormone receptor-positive (HR+), HER2-negative early breast cancer (EBC). Traditional manual methods are challenged by high patient volume, unstructured clinical notes, and limited research staffing. These barriers hinder recruitment efficiency and contribute to limited inclusion of all patient populations. To address these gaps, we deployed a Clinical Trial Patient Matching (CTPM) system powered by artificial intelligence (AI) and natural language processing (NLP) to enhance identification of eligible patients for two multi-site interventional trials: EMBER-4 (NCT05514054) and DARE (NCT04567420). Methods: The CTPM algorithm was deployed across 13 breast oncology sites within the Yale New Haven Health (YNHH) Smilow Cancer Hospital network. From September 2022 to May 2024, the system performed automated weekly pre-screening of all breast cancer patients seen across the network. CTPM extracted both structured and unstructured data from the electronic health record (EHR), applying trial-specific eligibility criteria for two multi-site interventional trials: EMBER-4 and DARE. Identified patient matches underwent manual chart review by a clinical research coordinator (CRC) to confirm eligibility prior to outreach and enrollment. Results: Between September 2022 and May 2024, the CTPM system pre-screened 45,380 unique breast cancer patients across YNHH. Based on trial-specific criteria, the system identified 429 patients as potentially eligible for EMBER-4 and 353 for DARE. Following manual chart review by CRCs, 263 patients were confirmed as eligible for EMBER-4 and 140 for DARE. For the EMBER-4 trial, CTPM identified 263 eligible patients, of whom 2.28% were aged 18-39, 26.6% were >70 years, 26.6% were racial/ethnic minorities, 6.1% NES, 22.8% Medicaid-insured, and 6.1% rural residents. Thirty-seven patients (13.81%) enrolled, with higher representation among racial/ethnic minorities (27.0%), patients > 70 years (13.5%), and Medicaid-insured patients (16.2%). For DARE, the 140 eligible patients identified by CTPM included 5.7% were aged 18-39, 22.1% were >70 years, 25.7% were racial/ethnic minorities, 8.6% NES, 24.3% Medicaid-insured, and 7.1% rural residents. Thirty-one patients (22.1%) enrolled in DARE, with notable representation among patients >70 years (22.6%), racial/ethnic minorities (19.4%), and Medicaid-insured (19.35%) patients. As a result of this enhanced identification and screening process, YNHH was a top enrollment site for patients nationally in both trials. Conclusions: This study presents the first prospective application of an AI-driven trial-matching system for high-risk HR+/HER2- EBC patients. Integration with EHRs enhanced identification of eligible patients, particularly among historically underrepresented groups. The subset of patients deemed ineligible after manual review reflects the difference between the CTPM system’s design— prioritizing sensitivity using a limited set of high-priority eligibility criteria from structured EHR data— and CRCs’ comprehensive reviews including unstructured clinical data not readily extractable through AI/NLP methods. While relaxed algorithm criteria minimized false negatives, we found that a two-tiered approach of broad AI-driven prescreening followed by expert validation supported efficient, scalable trial matching while preserving protocol fidelity. Yet, improved identification did not translate to proportional increases in consent or enrollment rates. To maximize clinical trial participation, AI tools like CTPM must be combined with expert review and targeted interventions that address downstream barriers to patient consent and enrollment.

N. Dalal¹, H. Tang², M. Reitsma³, J. Dickerson¹, S. Phillips³, B. Staiger⁴, J. Goldhaber-Fiebert³, J. Caswell-Jin¹; ¹Division of Oncology, Stanford University, Stanford, CA, ²Center for Population Health Sciences, Stanford University, Stanford, CA, ³Department of Health Policy, Stanford University, Stanford, CA, ⁴School of Public Health, UC Berkeley, Berkeley, CA.

Background: In 2017, the American Society of Clinical Oncology (ASCO) and Cancer Care Ontario (CCO) jointly published guidelines recommending discussion of adjuvant bisphosphonate therapy for all postmenopausal patients with early-stage breast cancer deemed candidates for systemic therapy. We evaluated the impact of this guideline on the use of adjuvant bone-modifying agents (BMAs) among patients in SEER-Medicare to understand if 1) the guidelines were effective in changing prescribing patterns and 2) there was a difference in the effect of the guidelines on specialized vs generalist oncologists.Methods: We identified women aged 65-85 years with localized or regional breast cancer diagnosed between 2012 and 2018 and continuously enrolled in Medicare fee-for-service for at least 1 year after diagnosis. We excluded patients with missing hormone receptor (HR) or HER2 status, no claims for surgery, radiation, or systemic therapy after diagnosis, death within 6 months of diagnosis, BMA use before breast cancer diagnosis, and those without an identifiable primary oncologist. Primary endpoints were: 1) use of a BMA within 1 year of diagnosis and 2) choice of bisphosphonate vs denosumab. We used multivariate logistic regression to examine the correlation of key factors (age, comorbidity, race/ethnicity, the treating oncologist’s degree of breast cancer specialization) with each endpoint. We report odds ratios (OR) and 95% confidence intervals (CI) from the multivariate analyses. We defined an oncologist’s breast cancer specialization as the percentage of patients with breast cancer they treated, relative to the total SEER-Medicare patients with colon, lung, or breast cancer. We designate oncologists with the highest quartile of breast cancer cases as “specialized” and the other 75% as “generalists.”Results: The cohort included N=76,498 patients. BMA use increased in HR+ disease from 7.4% (95% CI 6.8-8.0%) in 2012 to 12.1% (11.5-12.7%) in 2018, while there was no change in usage in HR- disease (2.2% [1.3-3.1%] in 2012 and 2.2% [1.4-3.0%] in 2018). Specialized oncologists used less BMA overall than generalist oncologists (OR 0.84 [0.80-0.89]). This difference was driven by lower BMA use by specialists in localized HR+ disease (OR 0.79 [0.74–0.84]), with no significant difference in regional or HR- disease (OR 0.97 [0.88–1.08]). There was no clear effect of the guideline publication on the temporal trend of overall BMA use. However, we observed an increase in the selection of bisphosphonate over denosumab after the guideline publication, with the proportion using bisphosphonate increasing from 21.5% (19.8-23.3%) (2015-2016) to 36.1% (34.2-38.0%) (2017-2018). This shift post-guideline was more pronounced in the specialized oncologists (p for interaction = 0.003); the proportion using bisphosphonate (vs denosumab) increased from 20.7% (17.9-23.6%) to 40.7% (37.5-43.8%) in specialized oncologists, compared to an increase from 22.0% (19.8-24.1%) to 33.4% (31.1-35.7%) in generalist oncologists. Overall, BMA use was higher for HR+ vs HR- disease (OR 4.40 [3.82-5.07]), regional vs localized stage (OR 1.17 [1.10-1.24]), older vs younger patients (OR 1.10 [1.04-1.16] for 75-85 vs 65-74), and Asian vs White patients (OR 1.38 [1.23-1.55]), and lower for Black vs White patients (OR 0.63 [0.55-0.71]). Conclusions: Specialized oncologists used adjuvant BMAs less frequently in patients with lower-risk HR+ disease compared to generalist oncologists. They were also more sensitive to the guideline release, demonstrating greater uptake of the recommendation for bisphosphonate over denosumab. Broader alignment with specialist prescribing patterns could promote more efficient resource utilization across the Medicare population.

S. K. Agrawal¹, M. Nadkarni², R. Ahmed¹, R. Sarin³; ¹Breast Oncosurgery, Tata Medical Center, kolkata, INDIA, ²Surgical Oncology, Kokilaben Dhirubahi Ambani Hospital and Medical Research Institute, Mumbai, INDIA, ³Surgical Oncology, Apollo Hospitals Indraprastha, Delhi, INDIA.

Background: In early-stage estrogen receptor-positive (ER+), HER2-negative breast cancer, adjuvant chemotherapy decisions are increasingly guided by the Oncotype DX (ODX) Recurrence Score (RS). However, the high cost of ODX limits its use in resource-constrained settings. NHS PREDICT, a validated clinical prognostic tool, is often used to estimate survival benefit from adjuvant therapy. This study aimed to assess the correlation between NHS PREDICT estimates and ODX RS, to evaluate whether NHS PREDICT can help identify patients who would benefit most from ODX testing.Methodology: This multicentric retrospective study included 320 patients with early-stage ER+/HER2− breast cancer who underwent ODX testing between January 2012 and May 2025 across 3 tertiary cancer centers in India. The study was approved by the Institutional Ethics Committee (Waiver No. 2025/TMC/350/IRB7). NHS PREDICT scores were calculated using the online PREDICT tool. Chemotherapy recommendations based on NHS PREDICT were derived via multidisciplinary team (MDT) discussions, while final decisions were based on ODX RS. Clinical data were retrieved from REDCap databases and institutional electronic records. Statistical analysis was performed using SPSS version 25.Results: The mean age was 57.5 ± 10.2 years, mean tumor size 2.57 ± 1.15 cm, Ki-67 24.0 ± 17.6%, ODX RS 17.9 ± 10.8, and NHS PREDICT chemotherapy benefit score 3.29 ± 2.35%. A weak, non-significant correlation was observed between ODX RS and NHS PREDICT benefit score (Pearson r = 0.060, p = 0.285).Concordance Between NHS PREDICT and ODX RS for Chemotherapy Decision-Making:

Clinical risk and Recurrence Score (RS) were concordant in 55.9%. Concordance was highest in postmenopausal node-negative patients (72.5%) and lowest in postmenopausal node-positive patients (43.8%). RS upgraded 23.8% of clinically low-risk patients, highest in premenopausal node-negative cases (36.7%) and lowest in postmenopausal node-positive cases (2.8%). RS downgraded 79.8% of clinically high-risk patients, most notably in postmenopausal node-positive cases (84.1%). On a median follow-up of 29 months (IQR 24-33), there were 8 recurrences (4 local, 4 distant) and 6 deaths (2 cancer-related). The 5-year estimated distant disease-free survival was 96.5%, and cancer-specific survival was 98.9%.Conclusion: In this large multicentric Indian cohort, concordance between NHS PREDICT and RS for adjuvant chemotherapy decision-making was poor. NHS PREDICT frequently overestimated chemotherapy benefit, especially in postmenopausal node-positive patients, where 84% were downgraded by RS. Notably, in postmenopausal node-positive patients with low predicted benefit on NHS PREDICT, only 2.8% were upgraded by RS, suggesting that Oncotype DX testing may be safely omitted in this subgroup. These findings support a selective, cost-effective testing strategy in resource-limited settings

R. Colombo Bonadio¹, L. Lapuchesky², M. C. Tavares³, N. C. Nunes⁴, L. Testa¹, I. Salas², M. Winocur², F. C. Balint³, I. M. de Sousa³, M. O. Andrade⁵, M. C. Gouveia⁶, F. Madasi⁷, J. Bines⁷, R. P. Ferreira⁸, D. D. Rosa⁸, C. L. Santos⁹, M. R. Monteiro¹⁰, Z. S. de Souza¹¹, D. Assad-Suzuki¹¹, C. dos Anjos¹², D. M. Gagliato¹³, A. U. Gomes¹³, B. M. Zucchetti⁶, A. Ferrari¹⁴, M. L. de Brito¹⁵, M. F. Monteiro¹⁶, P. A. Signorini¹⁷, N. J. Gomes¹⁸, G. G. Abuin², S. Sanches³, M. Tavares¹⁹, P. M. Hoff¹, M. Estevez-Diz²⁰, R. Barroso-Sousa⁵; ¹Oncology, Instituto D’Or de Pesquisa e Ensino, São Paulo, BRAZIL, ²Oncology, SUMA (Grupo Cooperativa Argentino para el estudio y la investigación del Cáncer de Mama), Buenos Aires, ARGENTINA, ³Oncology, A.C.Camargo Cancer Center, São Paulo, BRAZIL, ⁴Oncology, Grupo Américas, Rio de Janeiro, BRAZIL, ⁵Oncology, Brasilia Hospital, Oncologia Américas, Brasília, BRAZIL, ⁶Oncology, Hospital 9 de Julho, Grupo Américas, São Paulo, BRAZIL, ⁷Oncology, Instituto D’Or de Pesquisa e Ensino, Rio de Janeiro, BRAZIL, ⁸Oncology, Hospital Moinhos de Vento, Porto Alegre, BRAZIL, ⁹Oncology, Instituto D’Or de Pesquisa e Ensino, Recife, BRAZIL, ¹⁰Oncology, Grupo Americas, Hospital Samaritano, São Paulo, BRAZIL, ¹¹Oncology, Hospital Sírio-Libanês, Brasília, BRAZIL, ¹²Oncology, Hospital Sírio-Libanês, São Paulo, BRAZIL, ¹³Oncology, Hospital Beneficência Portuguesa, São Paulo, BRAZIL, ¹⁴Oncology, Hospital Santa Paula, Grupo Américas, São Paulo, BRAZIL, ¹⁵Oncology, Clínica AMO, Salvador, BRAZIL, ¹⁶Oncology, Instituto do Câncer do Ceará, Fortaleza, BRAZIL, ¹⁷Oncology, Centro Integrado de Pesquisa da Amazônia (CINPAM), Manaus, BRAZIL, ¹⁸Oncology, Hospital São Domingos, DASA Oncologia, São Luiz, BRAZIL, ¹⁹Oncology, Instituto D’Or de Pesquisa e Ensino, Salvador, BRAZIL, ²⁰Oncology, Instituto do Câncer do Estado de São Paulo, Faculdade de Medicina da Universidade de São Paulo, São Paulo, BRAZIL.

The High Unmet Need of Patients with Early Relapse After the KEYNOTE-522 Regimen – Evidence from the Neo-Real/GBECAM-0123 Study Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of tumor characterized by early disease recurrence, with most events occurring within the first two years after definitive treatment. With the adoption of the KEYNOTE-522 regimen—pembrolizumab (P) added to neoadjuvant chemotherapy (NAC)—we aimed to describe the patters and rates of early recurrence events in a real-world population treated with this regimen. Methods: The Neo-Real/GBECAM-0123 study is a real-world data analysis of patients with TNBC treated with P+NAC at sites in Brazil and Argentina since July 2020. The current analysis evaluated recurrence patterns following P+NAC. Early recurrence was defined as recurrence occurring during or within six months after completion of neoadjuvant/adjuvant therapy. Disease progression during NAC that precluded surgery was also classified as early recurrence. Recurrence occurring more than six months after therapy completion was considered late recurrence. Event-free survival (EFS) was calculated from diagnosis to either progression preventing surgery, recurrence, or death from any cause. Overall survival (OS) was calculated from diagnosis to death from any cause. Results: A total of 726 patients were included. The median age was 44 years (range 21-91). Most patients had stage II disease (70.5%), grade 3 tumors (68.9%), and Ki-67 index ≥50% (71.1%); 105 patients (14.5%) had a known pathogenic BRCA1/2 variant.After a median follow-up of 22 months, 74 patients (10.2%) experienced disease recurrence, and 8 patients (1.1%) died without recurrence. The 2-year EFS was 86.9%. Among those with recurrence, 50 (67.6%) were classified as early (including 4 patients with disease progression during P+NAC, which precluded surgery) and 24 (32.4%) as late recurrences.Early recurrence occurred in 2.1% of patients with pCR and in 15.2% of those with residual disease (P < 0.001). From another perspective, among patients with early recurrence after surgery (n = 46), 80.4% (n = 37) had residual disease at surgery, while 19.6% (n = 9) had achieved pCR.Most patients with early recurrence received adjuvant therapy. In patients with pCR, 8 out of 9 (88.9%) received adjuvant P. Among patients with residual disease, 32 out of 37 (86.5%) received adjuvant treatment, including P plus capecitabine in 19 (51.3%), P alone in 6 (16.2%), capecitabine alone in 6 (16.2%), P plus Olaparib in 1 (2.7%). 5 patients (13.5%) received no adjuvant therapy, mainly due to early relapse.Among patients with pCR, the main recurrence sites were the central nervous system (CNS) (33.3%), lymph nodes (22.2%), pleura (22.2%), and locoregional (14.3%). For those with residual disease, the main sites were locoregional (33.3%), lymph nodes (24.3%), CNS (21.6%), bones (21.6%), lung (13.5%), and liver (13.5%).Post-recurrence deaths occurred in 18 patients with early relapse and 7 with late relapse. The 2-year OS rate in the overall cohort was 95.6%. Among patients with recurrence, the 2-year OS rate was 62.3% for those with early relapse and 91.0% for those with late relapse. Discussion: The majority of recurrences after the KEYNOTE-522 regimen occurred early. These patients are resistant to four chemotherapeutic agents and an immune checkpoint inhibitor (ICI) and face markedly poor survival outcomes. Our findings underscore a critical unmet need for effective therapeutic options in this population, which is often excluded from clinical trials investigating first-line regimens, including studies of antibody-drug conjugates combined with ICIs.

A. Bounedjar¹, M. A. Melzi¹, H. Mahfouf², A. Dib³, C. Sedkaoui⁴, H. Djeddi⁵, E. Kerboua², W. Benbrahim⁶, T. Filali⁷, H. Zidane⁸, F. Seghier⁹, D. Yekrou¹⁰, F. Bereksi¹¹, A. Bensalem⁷, B. Larbaoui¹¹, A. Bousahba¹¹, M. Abada¹², R. Miloudi¹², M. A. Bahi¹³, H. Fizi¹⁴, A. Djellaoui¹⁵, F. Benmhidi¹⁵, K. Kouidri¹⁶, N. Boualaoui¹⁷, Z. Benlahreche¹⁸, M. Oukkal²; ¹Laboratoire de Recherche en Cancérologie, University of Blida 1, Blida, ALGERIA, ²Faculty of medecine, University of Algiers 1, Algiers, ALGERIA, ³Faculty of medecine, University of Setif, Setif, ALGERIA, ⁴Faculty of medecine, University of Tizi Ouzou, Tizi Ouzou, ALGERIA, ⁵Faculty of medecine, University of Annaba, Annaba, ALGERIA, ⁶Faculty of medecine, University of Batna, Batna, ALGERIA, ⁷Faculty of medecine, University of Constantine, Constantine, ALGERIA, ⁸Faculty of medecine, University of Mostaganem, Mostaganem, ALGERIA, ⁹Faculty of medecine, University of Blida 1, Blida, ALGERIA, ¹⁰Faculty of medecine, University of Sidi Belabes, Sidi Belabes, ALGERIA, ¹¹Faculty of medecine, University of Oran, Oran, ALGERIA, ¹²Medical oncology department, Public hospital of Ain Defla, Ain Defla, ALGERIA, ¹³Medical oncology department, Public hospital of El Oued, Oued Souf, ALGERIA, ¹⁴Medical oncology department, Anti cancer center of Ouergla, Ouergla, ALGERIA, ¹⁵Medical oncology department, Public hospital of Medea, Medea, ALGERIA, ¹⁶Medical oncology department, Anti cancer center of Adrar, Adrar, ALGERIA, ¹⁷Medical oncology department, Public hospital of Aflou, Aflou, ALGERIA, ¹⁸Faculty of medecine, University of Laghouat, Laghouat, ALGERIA.

Background : Breast cancer is the most frequently diagnosed cancer among women in Algeria, accounting for 46.0% of all female malignancies, with 13,161 new cases reported in 2022 according to the National Network of Cancer Registries. This trend is consistent with global estimates from GLOBOCAN, which also identify breast cancer as the leading cause of cancer among women worldwide. Despite its public health burden, national-level epidemiologic and clinicopathologic data on breast cancer in Algeria remain scarce. Most available studies are single-center or regional, limiting their generalizability. Furthermore, North African populations, including Algerian women, have distinct lifestyle, reproductive, and sociodemographic characteristics compared to Western populations, which may influence disease presentation and biology. To address this gap, we conducted a large, retrospective, multicenter study aiming to describe the demographic, clinical, and pathological characteristics of Algerian breast cancer patients diagnosed in 2024, based on real-world data from major oncology centers across the country. Patients and Methods : We conducted a national, retrospective, multicenter study involving 23 oncology centers across Algeria. Eligible participants were female patients diagnosed and treated for breast cancer between January 1 and December 31, 2024. Data were collected from medical records as part of real-world clinical practice. Variables extracted included age at diagnosis, menopausal status, family history of cancer, clinical stage at presentation, histological type and grade, estrogen receptor (ER), progesterone receptor (PR), HER2 status, Ki67 index, and molecular subtype classification. All data were anonymized and centralized in a secure national database. Descriptive analyses were planned to summarize the demographic, clinical, and pathological characteristics of the study population. Results : A total of 6,044 women with breast cancer diagnosed in 2024 were included from 23 oncology centers across Algeria. The median age at diagnosis was 52 years (range: 20-86), and 60% of patients were postmenopausal. The majority of tumors were detected through self-examination (67.72%), while screening accounted for only 4.17% of cases. The left breast was affected in 48.99% of cases, the right breast in 48.25%, and bilateral involvement was observed in 2.76%. Invasive carcinoma of no special type was the predominant histology (79.90%). Grade III tumors (SBR) accounted for 19.33% of cases. Molecular subtypes were distributed as follows: luminal B (49.33%), luminal A (18.11%), HER2-positive (20.70%), and triple-negative (11.86%). Tumor size distribution showed 13.63% of cases were T1. Advanced tumors (non-inflammatory T4a/b/c) were found in 21.56%, and inflammatory breast cancer (T4d) in 4.74%. Node-negative disease (N0) was present in 36.87%, while N3 involvement was seen in 3.54%. Distant metastases at diagnosis were documented in 15% of patients. The median time to initial treatment was 50.5 days. Conclusion: This large, retrospective multicenter study provides the first national real-world overview of breast cancer in Algeria. The majority of patients presented with luminal subtypes, but a substantial proportion had locally advanced (T4: 26.3%) or metastatic disease (15%) at diagnosis. Most tumors were detected through self-examination, while organized screening remained limited. The observed diagnostic and treatment delays, as well as the frequency of advanced-stage presentation, highlight the urgent need to strengthen early detection programs and promote timely access to care across the country. These findings serve as a foundation for future national strategies aimed at improving breast cancer outcomes in Algeria.

M. C. Anyanwu¹, A. Raza², A. Nawaz³, U. Khan⁴; ¹Dubin Breast Cancer, Icahn School of Medicine at Mount Sinai, New York, NY, ²Medical Sciences, Services Institute of Medical Sciences, Lahore, Pakistan, Pakistan, PAKISTAN, ³Medical Sciences, Pakistan Atomic Energy Commission Hospital, Islamabad., Islamabad, PAKISTAN, ⁴Cardiovascular diseases, University of Maryland School of Medicine, Baltimore, Baltimore,, MD.

Background: Advances in breast cancer treatment have improved survival outcomes, with the 5-year survival rates approximately 99% for early-stage breast cancer patients. Despite these therapeutic achievements, cardiovascular complications, particularly heart failure (HF), have emerged as a leading cause of non-cancer mortality among breast cancer survivors aged 65+, thereby compromising long-term survival and posing a greater mortality risk than cancer itself. We aim to analyze trends in HF-related mortality among women with breast cancer in the U.S. over two decades (1999-2020) and highlight key demographic and regional disparities. Methods: We used the CDC WONDER (Wide-ranging ONline Data for Epidemiologic Research) mortality database to extract age-adjusted mortality rates (AAMRs) per 100,000 US women aged ≥25 years for breast cancer and HF mortality from 1999 to 2020. The Joinpoint Regression Program calculated the average annual percentage change (AAPC) in AAMRs. Results: From 1999 to 2020, HF caused 56,006 deaths among U.S. women with breast cancer, with a decline over time (AAPC: -1.16%; 95% CI: -1.50 to -0.86). The overall AAMR was 1.94 (1.93 – 1.96). Older adults (≥65 years) showed a significantly higher AAMR [8.88 (8.80 – 8.96)] with an AAPC of -1.17% (-1.45 to -0.93) than younger adults (25-64 years) [0.26 (0.25 – 0.27)] with an AAPC of -1.24% (-2.37 to -0.36). Among the racial and ethnic groups, the highest AAMR was observed in non-Hispanic (NH) Blacks [2.37 (2.31 – 2.43)], followed by NH Whites [2.03 (2.01 – 2.05)], Hispanics [0.98 (0.94 – 1.03)], and NH Asians or Pacific Islanders [0.66 (0.61 – 0.72)]. NH Blacks showed the highest mortality burden and a slight increase in AAMRs [AAPC: 0.15% (-0.48 to 0.66)]. NH Asians or Pacific Islanders showed the lowest mortality burden with the highest decline in AAMRs [AAPC: -1.47% (-2.71 to -0.28)], followed by Hispanics or Latinos (-1.27%) and NH Whites (-1.01%). Regionally, the Midwest showed the highest AAMR [2.25 (2.21 – 2.29)], followed by the West [1.95 (1.92 – 1.99)], the Northeast [1.85 (1.81 – 1.88)], and the South [1.81 (1.78 – 1.83)]. The Northeast showed the highest decline in AAMRs [AAPC: -1.48% (-2.06 to -0.98)], and the South showed the lowest [-0.59% (-0.99 to -0.20)]. Women in non-metropolitan areas had higher AAMRs [2.36 (2.32 – 2.41)] than those in metropolitan areas [1.87 (1.85 – 1.88)]. Metro and non-metropolitan regions showed a similar decline in AAMRs over the study period (-1.05% vs. -1.20%). Conclusion: HF-related mortality among U.S. female breast cancer survivors has declined over the past two decades; however, older adults, NH Blacks, patients residing in the Midwest, and non-metropolitan areas experienced higher mortality burdens, highlighting the need for targeted interventions that incorporate risk stratification, integrated cardiovascular surveillance and equity centered interventions into survivorship planning. Ultimately, addressing demographic and regional disparities is essential to improving long-term survival outcomes for breast cancer survivors.

V. Kaklamani¹, S. Valliant², S. Hunter³, O. Tymejczyk⁴, A. Yu⁵, P. Earla⁶, S. Mehta⁷, E. Pang⁸; ¹Medicine, UT Health San Antonio, San Antonio, TX, ²Global Oncology HEOR, V&E, Daiichi Sankyo, Inc., Basking Ridge, NJ, ³RWE, Daiichi Sankyo, Inc., Basking Ridge, NJ, ⁴Global Oncology RWE Generation, Daiichi Sankyo, Inc., Basking Ridge, NJ, ⁵Global Scientific & Medical Affairs Oncology, Merck & Co., Inc, Rahway, NJ, ⁶Outcomes Research Value & Implementation (V&I), Merck & Co., Inc., Rahway, NJ, ⁷HEOR, Daiichi Sankyo, Inc., Basking Ridge, NJ, ⁸Global Oncology Medical Affairs, Daiichi Sankyo, Inc., Basking Ridge, NJ.

Background Endocrine therapy (ET) in combination with a cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) is a preferred first-line (1L) treatment for patients (pts) with HR+/HER2− mBC. However, ET resistance frequently emerges after 1L treatment, with many pts receiving subsequent chemotherapy or other targeted regimens. This study aimed to assess treatment patterns and clinical outcomes in pts with HR+/HER2− mBC that progressed on 1L ET + CDK4/6i in real-world (rw) practice settings. Methods This was a noninterventional, retrospective, observational cohort study using the US-based Flatiron Health Enhanced Datamart. Adult pts with HR+/HER2− mBC (with no other actionable genomic alterations [ESR1, PIK3CA, AKT1, PTEN, or gBRCA]) that progressed on 1L ET + CDK4/6i were included if they initiated a second-line (2L) therapy between Jan 2017 and Sep 2024 with ≥90 d of potential follow-up. Pt demographics, clinical characteristics, and treatment utilization were assessed descriptively. Treatment data were recorded as documented by physicians and may reflect off-label use. The primary (rw progression-free survival [rwPFS]) and secondary (rw overall survival [rwOS], rw time to discontinuation or death [rwTTD/D], and rw time to next treatment or death [rwTTNT/D]) endpoints were assessed using Kaplan-Meier methods. Analyses were performed in all pts, by 2L regimen, and by time to progression on 1L treatment. Results 1415 pts with HR+/HER2− mBC were included (median age, 65 y; 66.2% were White). Of these, 57.3% (n=811) had disease progression on ET + CDK4/6i within 12 mo of 1L initiation (early progression; 33.3% in ≤6 mo); 25.5% had disease progression in 12 to 24 mo and 17.2% within >24 mo. In the 2L, 63.6% of pts received an ET-based regimen, 27.1% received chemotherapy (CT; monotherapy, 23.8%; multiagent, 3.3%), and 9.3% received other regimens (including AKTi, PARPi, and the ADC sacituzumab govitecan or trastuzumab deruxtecan). Pts with early vs later times to disease progression on 1L ET + CDK4/6i used 2L CT more frequently (40.6% [≤6 mo] vs 14.0% [>24 mo]); the opposite was true for 2L ET (52.2% [≤6 mo] vs 75.3% [>24 mo]). With a median follow-up of 14.6 mo, the 2L median rwPFS ranged from 4 to 8 mo and median rwOS ranged from 14 to 32 mo; the shortest estimates were among pts on 2L CT and with early disease progression on 1L ET + CDK4/6i (Table). Conclusions In this study of pts with HR+/HER2− mBC that progressed on 1L ET + CDK4/6i, over half had 1L disease progression within 12 mo and about one-third received CT in a subsequent line. The median rwPFS on 2L treatments was shorter among those who were using CT in 2L or had early progression (<12 months) on 1L ET + CDK4/6i, highlighting the emergence of ET resistance and a need for more effective therapeutic alternatives to improve pt outcomes.

A. Danilova¹, P. Shilo², I. Nigmatullina¹, D. Stroyakovskiy¹; ¹Medical oncology, Moscow City Oncology Hospital 62, Stepanovskoe, RUSSIAN FEDERATION, ²Medical oncology, Lahta clinic, Saint Petersburg, RUSSIAN FEDERATION.

Background: Invasive lobular carcinoma (ILC) is a distinct histological subtype of hormone receptor-positive/HER2-negative (HR+/HER2−) breast cancer, accounting for up to 15% of cases. Despite its unique clinical behavior, patients with ILC have been underrepresented in pivotal CDK4/6 inhibitor trials, and real-world data on treatment outcomes in this population remain limited.Methods: We conducted a retrospective study of patients with metastatic ILC treated with CDK4/6 inhibitors at City Clinical Hospital No. 62 (Moscow) from 2015 to 2023. Among 803 patients with HR+/HER2− metastatic breast cancer, 141 had confirmed ILC. Demographic, clinical, and treatment-related data were extracted from medical records. Survival outcomes were estimated using the Kaplan-Meier method, and comparisons between subgroups were performed using log-rank tests.Results: The median age was 60 years, and the median follow-up was 46 months. Most patients had grade 2 tumors (82.9%) and high ER expression (Allred 8 in 72.3%). At the time of CDK4/6 inhibitor initiation, 64.7% received treatment in the first line. The most frequently used agents were palbociclib (49.3%) and ribociclib (45.7%), while abemaciclib was prescribed in 5% of cases. The median overall survival (OS) in the full ILC cohort was 49 months (95% CI: 46.1-51.9). When stratified by CDK4/6 inhibitor, the median OS was 50 months for palbociclib (95% CI: 46.4-53.6), 44 months for ribociclib (95% CI: 32.9-55.1), and not reached for abemaciclib, with no statistically significant differences between groups (log-rank p=0.276). The median progression-free survival (PFS) was 30 months overall (95% CI: 22.2-37.8), with 32 months for palbociclib, 30 months for ribociclib, and 17 months for abemaciclib (p=0.156). Subgroup analyses showed no significant differences in OS by age (<60 vs ≥60; p=0.620), presence of bone (p=0.316), liver (p=0.854), or lung metastases (p=0.410). The type of endocrine backbone (aromatase inhibitor, fulvestrant, or exemestane) was not associated with differences in OS (p=0.778). Patients treated in the first line had longer OS (49 months) compared to those treated after progression on prior therapies (30 months), though the difference did not reach statistical significance.Conclusions: In this real-world cohort of patients with metastatic ILC, CDK4/6 inhibitors demonstrated clinically meaningful survival outcomes consistent with previously reported results in broader HR+/HER2− populations. No significant differences in OS or PFS were observed between individual CDK4/6 inhibitors or across clinical subgroups. These findings support the use of CDK4/6 inhibitors in ILC, while highlighting the need for prospective studies to better define optimal treatment strategies in this distinct population.

C. Pereira dos Santos, M. Celeleste Tavares, C. Campanholo Marques, S. Moraes Sanches; Oncology, Hospital A.C Camargo Cancer Center, São Paulo, BRAZIL.

Title:Impact of Body Mass Index on the Efficacy and Safety of Adjuvant Abemaciclib in a Real-World Brazilian Cohort of Patients With High-Risk Early Breast CancerBackground:Obesity is an increasing concern in breast cancer, influencing both prognosis and treatment tolerance. While abemaciclib has demonstrated efficacy in high-risk HR (hormone receptor) +/HER2- patients, real-world evidence regarding its safety and efficacy across BMI (body mass index) categories remains limited.Methods:We conducted a retrospective and prospective, observational study involving 146 patients who received adjuvant abemaciclib combined with endocrine therapy between January 2021 to June 2025 at a comprehensive cancer center. Patients were stratified by BMI (kg/m²) as obese (≥30), overweight (25 ≤ BMI < 30), and non-overweight (<25). We assessed treatment-related toxicities, dose reductions, pathological response to neoadjuvant chemotherapy (RCB), recurrence, and disease-free survival. Statistical analyses included chi-square tests, Spearman correlation, Kaplan-Meier survival curves, and Cox regression.Results:Obese patients experienced higher rates of dose reduction (72%) compared to non-obese (47%) and overweight patients (29%), although the difference did not reach statistical significance (p = 0.075). Regarding neoadjuvant response, non-overweight patients achieved more RCB-0 (complete response), while 30.8% of obese patients had RCB-III (high residual disease). Although no significant association was found between BMI and RCB (p = 0.135), a clinical trend was observed. Larger tumors (>5 cm) were more frequent in obese patients (23.1%) compared to non-obese (14.3%).Anemia showed a positive correlation with BMI (Spearman p = 0.043), with a higher frequency in obese patients (27.3%) versus non-overweight (15.2%). No statistically significant associations were observed between BMI and other toxicities (diarrhea, neutropenia, transaminase elevation, arthralgia).Four recurrences were documented: three in obese and one in a non-overweight patient. Kaplan-Meier curves suggested a trend toward longer disease-free survival among obese patients (median: 641 days) compared to non-overweight patients (237 days). However, this finding did not reach statistical significance (Cox regression HR = 2.6; p = 0.235). ANOVA for time to recurrence showed a significant difference between BMI groups (p = 0.003), favoring delayed recurrence in obese patients.Conclusion:In this real-world Brazilian cohort, obesity was associated with higher rates of dose reduction due to toxicity, lower pathological response to neoadjuvant chemotherapy, and larger tumors. Paradoxically, obese patients demonstrated longer disease-free survival, a finding consistent with the “obesity paradox” described in the literature. These results highlight the need for further research into the complex role of body composition in HR+/HER2- breast cancer treated with CDK4/6 inhibitors.

M. Shah, S. Patel, T. Shah, D. G. Vijay, S. Alurkar; Medical oncology, HCG Aastha Cancer Center, Ahmedabad, INDIA.

Background:Breast cancer has emerged as the most prevalent malignancy among women in India. Its epidemiological pattern in the Indian subcontinent differs significantly from that seen in Western countries. One of the most notable differences is the earlier age of onset in Indian women. In young women, breast cancer poses unique challenges due to its aggressive biological behaviour, concerns regarding fertility, and worse outcomes. This study aims to evaluate the clinicopathological characteristics, treatment approaches, and clinical outcomes of patients aged 40 years or younger, treated at a tertiary cancer center.Methods:We retrospectively analyzed the records of 102 breast cancer patients aged ≤40 years, presented between January 2023 and February 2025 at HCG Aastha cancer center Ahmedabad. Data were collected on demographics, family history, genetics, tumor histology, staging, receptor status, treatment modalities, and recurrence. Results:The median age was 36 years (range 21 to 40 years). 4.9% of the patients were nulliparous, and 75.5% had no family history of malignancy. Genetic testing was done in 40 patients (39.2%). Among them, results were positive in 19 patients (18.6%), negative in 16 patients (15.7%), and showed variants of uncertain significance (VUS) in 5 patients (4.9%). Among these, BRCA mutations were predominant. In 51% of patients, genetic testing was advised but, they did not undergo the testing. Histology revealed Invasive Ductal Carcinoma (IDC) in 97 (95.1%) patients. Imaging for diagnosis primarily included bilateral mammography (79.4%). MRI and PET-CT were used in selected cases. Stage II was the most common stage at diagnosis, observed in 51 patients (50%), followed by Stage IV in 20 patients (19.6%). Hormone receptor positive, HER2neu negative was observed in 42 patients (41.1%), while both hormone receptor and HER2neu positivity were seen in 31 patients (30.4%). HER2neu positivity alone was noted in 9 patients (8.8%), triple-negative breast cancer (TNBC) was found in 15 patients (14.7%). Mammogram showed mainly dense breasts, well circumscribed and multicentric lesions. Surgical management was offered to the majority of patients who did not present with Stage IV disease. Among them, breast-conserving surgery (BCS) was performed in 34 patients (33.3%), while modified radical mastectomy (MRM) was performed in 33 patients (32.4%), indicating a nearly equal distribution between the two surgical approaches. Neoadjuvant chemotherapy (NACT) was given to 28 patients (27.4%), of whom 5 achieved a pathological complete response (pCR). Most patients remained on follow-up, with 10.8% experiencing disease recurrence. Among these, sites of recurrence included bone-only (1.9%), brain-only (1.9%), visceral-only (1.9%), and combined bone and visceral metastases (4.9%). Nearly half of the patients (47.1%) had no recurrence, while 40.2% were lost to follow-up. Recurrences were predominantly seen in those initially diagnosed with Stage II and III disease.Conclusion:Young women (</= 40 years) with breast cancer present with stage II-III disease, multicentric lesions that can be picked up on digital mammography most of the times. Most common subtype is hormone positive breast cancer, and 18% were deteced with germline mutations, BRCA being the most common. Recurrence was observed even in early-stage cases, underscoring the need for vigilant follow-up. Multidisciplinary care, including routine genetic counselling, remains essential. Future research should prioritize fertility preservation, psychosocial support, and long-term outcomes in this high-risk population.

J. Hundal¹, D. Parekh², A. Harisingani³, A. Abushamma⁴, Omer Ashruf, J. Sukumar⁵; ¹Taussig Cancer Institute, Cleveland Clinic, Clevelan, OH, ²Internal Medicine, SUNY Upstate Medical Univeristy, Syracuse, NY, ³Internal Medicine, Loyola Medicine MacNeal Hospital, Berwyn, IL, ⁴Internal Medicine, Akron General Medical Ctr, Akron, OH, ⁵Hematology and Oncology, MD Anderson Cancer Institute, Houston, TX.

Background:Obesity and cardiometabolic dysfunction are common in breast cancer survivors and linked to higher treatment toxicity, cardiovascular morbidity, and worse outcomes. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), including semaglutide and Tirzepatide, show cardiometabolic benefits in non-cancer populations, but their impact in breast cancer survivors remains unclear. This study compared the effects of semaglutide and Tirzepatide versus metformin on weight trajectory and major adverse cardiovascular events (MACE) in a real-world oncology cohort.Methods:We conducted a retrospective cohort study using the TriNetX Analytics Research Network, a federated, de-identified electronic health record database. Female breast cancer patients with obesity and/or type 2 diabetes mellitus who were prescribed semaglutide (n=3,009) or Tirzepatide (n=1,652) from January 1, 2018, to June 1, 2025, were identified and matched 1:1 to metformin users without GLP-1 RA exposure using propensity scores. Baseline characteristics included demographics, comorbidities, cancer therapies, and cardiometabolic risk factors. Matching was performed using age, sex, race, BMI, hemoglobin A1c, and comorbidities. Outcomes included weight change at 12 and 24 months, and incidence of MACE, defined as myocardial infarction, stroke, or cardiovascular death. Cox proportional hazards models estimated hazard ratios (HRs) and 95% confidence intervals (CIs).Results: At 12 and 24 months, both semaglutide and Tirzepatide groups demonstrated significantly greater weight loss compared to matched metformin users (Table 1). Semaglutide was associated with a significant reduction in MACE versus metformin (HR 0.78, p=0.032), including MI (HR 0.68, p=0.045), with favorable trends in cardiovascular death (HR 0.75, p=0.07) and stroke (HR 0.81, p=0.18). Tirzepatide demonstrated more pronounced cardioprotective effects, reducing MACE (HR 0.63, p=0.001), MI (HR 0.52, p=0.004), and cardiovascular death (HR 0.61, p=0.033), with a trend toward stroke reduction (HR 0.72, p=0.09). Conclusions:In this real-world analysis of breast cancer patients with cardiometabolic comorbidities, both semaglutide and Tirzepatide led to clinically meaningful and sustained weight loss at 12 and 24 months and reduced cardiovascular risk, with Tirzepatide showing the greatest benefit. Our findings underscore the potential of GLP-1 receptor agonists to improve cardiometabolic health, a key modifiable risk factor in breast cancer survivors, by enhancing weight and cardiovascular outcomes. These results support the role of GLP-1 receptor agonists as adjuncts to lifestyle interventions in survivorship care. Prospective trials in breast oncology populations are needed to confirm these findings and guide the integration of strategies for cardiovascular, metabolic, and cancer risk reduction.

T. Ackbarali¹, L. Braithwaite², C. Tellez³, S. Tolaney⁴; ¹Hematology/Oncology Team, Medlive, Lake Worth, MA, ²Cancer Center, University of Wisconsin-Carbone Cancer Center, Madison, WI, ³Hispanic Breast Cancer Clinic, Northwestern University, Chicago, IL, ⁴Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA.

BACKGROUND: In recent years, TNBC has transformed from a difficult-to-treat malignancy with few effective treatment options into an active area of research, where new treatments are emerging each year. As novel treatments are established in advanced disease settings, and the focus of research turns to improving options in earlier stages of disease, it is important that oncologists remain up to date on the current and future care of patients with TNBC. This is particularly important for Hispanic and Latina patients, who face numerous disparities in treatment access and quality of care. A tethered educational initiative was designed to ensure that clinicians and patients/caregivers stay up-to-date on current and emerging TNBC treatments, disparities in Hispanic/Latina populations, and strategies to improve quality of care. METHODS: Two, interactive, video-based programs were designed for patients/caregivers, and clinicians in collaboration with Surviving Breast Cancer and Salud America. The programs were hosted on Medlive.com from April 2024 to June 2025. Patients were interviewed and their real-world stories embedded within the program. We report on an analysis of patient outcomes and the intersection of patient and clinician perspectives, including behavioral impact, and qualitative insights. RESULTS: To date, more than 2,273 clinicians have engaged with the education program and over 70,000 views via social media of the patient/caregiver program. Of participating patients/caregivers, 80% were non-White (50% Hispanic/Latina) and 78% were people diagnosed with breast cancer, 22% of whom had TNBC. Following the program, 82% felt confident discussing a treatment plan with their healthcare team, and 71% were likely to consider participating in a clinical trial. Qualitative data elucidating specific intended changes and patient experiences will be shared. Patients/caregivers prioritized community-centric resources more than HCPs recognized. Ethnicity-specific barriers were felt more strongly by patients. Of the participants in the clinician program, 80% were physicians, 76% of whom noted their specialty as oncology. Increased recognition (42%) of ADCs as the preferred second-line option for biomarker-negative TNBC, reflected by a rise in ADC selection post-activity.​ Improved understanding (47%) of immune checkpoint inhibitor toxicities, though some learners may still underestimate long-term endocrine-related side effects.​ Modest gains in awareness of racial disparities in TNBC, suggesting clinicians recognize inequities but may need further education on actionable solutions.​ CONCLUSIONS: The disparities highlight the importance of culturally attuned approaches that extend education and support to familial/social networks, which are often critical for patients from Hispanic and Latina populations.​ Ethnicity-specific barriers highlights a disconnect in recognizing the importance of peer representation and cultural similarity within support networks, which can greatly affect patient comfort and outcomes.​ ​These findings underscore a notable disconnect between what patients/caregivers prioritize and what clinicians perceive as their challenges. Patients tend to emphasize the importance of community and cultural representation in support systems, while HCPs focus on logistical barriers, such as language services. ​​Bridging this gap requires a dual focus: addressing systemic barriers while fostering culturally tailored support networks that resonate with patients’ lived experiences.​ Support was provided by an independent educational grant from Gilead Sciences, Inc.

V. Prasath¹, A. N. Riner², J. Kim³, A. Clark², B. Slover³, R. Wesolowski¹, J. C. Kai¹, S. Jhawar⁴, C. Spears⁵, B. A. Oppong², S. D. Sardesai¹; ¹Medical Oncology, The Ohio State University College of Medicine, Columbus, OH, ²Surgery, The Ohio State University College of Medicine, Columbus, OH, ³Biomedical Informatics, The Ohio State University College of Medicine, Columbus, OH, ⁴Radiation Oncology, The Ohio State University College of Medicine, Columbus, OH, ⁵Medical Genetics, The Ohio State University College of Medicine, Columbus, OH.

Introduction: There is conflicting evidence on the prognosis of patients with HER2-negative early breast cancer (HER2- eBC) and germline pathogenic variants (PV) including BRCA1, BRCA2, PALB2, ATM, and CHEK2. Studies are limited by marked heterogeneity and a small number of evaluable patients. Here, we present treatment patterns and prognosis in hereditary breast cancer(BC) susceptibility gene mutation carriers with HER2- eBC from CancerLinQ, a health technology platform comprised of de-identified real-world data from over 2.5 million patients across the United States. Methods: Patients with stage I-III HER2- eBC diagnosed between 2002-2023 were identified in CancerLinQ. Those with germline PVs in BRCA1, BRCA2, PALB2, ATM, and CHEK2 constituted the mutation carrier (MC) group while those with negative genetic testing made up the non-MC group. Demographics, pathology findings, genomic testing, and cancer treatment data were extracted. Patients with metastases within 9 months of diagnosis, and patients without stage information, and those without germline genetic testing were excluded. The primary outcome was recurrence free survival (RFS). Secondary objectives included overall survival (OS) and utilization rate of contralateral prophylactic mastectomy (CPM) in each group. RFS and OS were presented with Kaplan-Meier curves and were analyzed with the Cox proportional hazard regression method. Results: 1105 patients with germline PVs in BRCA1 (360,32.6%), BRCA2 (461,41.7%), PALB2 (76,6.9%), ATM (67,6.1%), and CHEK2 (91,8.2%) constituted the MC cohort; the non-MC cohort included 2129 patients. The MC cohort had a younger age at diagnosis and a higher rate of triple negative and nodal disease (p<0.05). The MC group also received neoadjuvant chemotherapy more frequently and had a higher pathologic complete response rate. The adjusted RFS was improved for the non-MC group (HR 0.84,p=0.019) in comparison to the MC cohort; however, there was no statistically significant difference in OS between groups or by gene mutation. CPM use was more common in patients younger than 50 years and differed by gene mutation (p<0.05). CPM vs breast conserving therapy or therapeutic mastectomy showed improved adjusted RFS (p=0.04) and OS (p=0.007) in the MC cohort. Black patients demonstrated worse OS (HR 1.3,p=0.005) regardless of MC status. Conclusions: This is one of the largest real-world analyses of hereditary BC susceptibility gene MCs with HER2- eBC. The MC group reported worse RFS. CPM use was more common in younger patients and in those with PVs in BRCA1/2. CPM use was independently associated with improved OS in MC group. This highlights the need for timely genetic testing and identification of at-risk patients who will benefit from personalized treatment approaches. Table 1:

H. M. Johnson¹, W. Dong¹, Y. Shen¹, W. Irish², J. H. Wong², N. A. Vohra², N. Tamirisa¹; ¹Breast Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ²Surgery, East Carolina University, Greenville, NC.

Background: Accumulating evidence supports age at diagnosis as an independent prognostic variable for breast cancer-specific and overall survival (OS). Using SEER data, we previously developed a novel prognostic staging system that incorporates age at diagnosis and demonstrated more refined risk stratification compared with the current American Joint Committee on Cancer (AJCC) staging schema. We now aim to externally validate this novel breast cancer staging system. Methods: The National Cancer Database was used to identify adult females diagnosed with invasive breast cancer from 2010-2015. Women with prior history of malignancy, unknown vital status, or unknown AJCC clinical prognostic stage (CPS) variables were excluded. Serial multivariable Cox’s proportional hazards models were used to evaluate associations between OS and CPS +/- age +/- effect modification between CPS and age. Models were evaluated using the Akaike information criterion (AIC). Results: Among 663,659 patients, the median age was 60 years (IQR 51-70) and the median follow-up was 91.3 months (95% CI 91.2-91.4). At last follow-up, 133,273 patients (20.1%) were dead. The model that incorporated both age and effect modification had the lowest AIC (3320681, versus 3400173 for the model excluding age and 3326910 for the model including age without effect modification), indicative of the best fit. This model was used to predict OS at various timepoints, stratified by CPS. Within each stage group, differential survival was seen across the age spectrum, consistent with the initial model developed in SEER (Table). Within each stage group from IB-IIIC, women diagnosed at age 40 had the best survival, whereas women at the extremes of age had inferior survival. For example, 3-year OS for patients with stage IIIA disease was 0.648 across all ages, highest (0.831) for patients diagnosed at age 40, lower (0.714) for age 20, and lowest (0.127) for age 90. Conclusion: This analysis provides external validation of our novel prognostic staging system for breast cancer. Including age at diagnosis as a prognostic variable results in more refined risk stratification across all AJCC stage groups. Future editions of AJCC should consider utilization of not only anatomic and pathologic variables, but also age at diagnosis, to achieve more accurate survival predictions. While poorer OS is expected for older women due to age-related competing mortality risks, further research is necessary to understand why younger women with breast cancer have higher morality than those diagnosed closer to age 40.

R. Moreira¹, D. Huo², A. Pearson³, I. Small⁴, O. Olopade³, J. Bines¹, F. Howard³; ¹Oncology, Instituto Nacional de Cancer, Rio de Janeiro, BRAZIL, ²Department of Public Health Sciences, University Chicago Medicine, Chicago, IL, ³Oncology, University Chicago Medicine, Chicago, IL, ⁴Data Management and Analysis, Instituto Nacional de Cancer, Rio de Janeiro, BRAZIL.

Purpose Genomic assays are unavailable in Brazil’s public health system and are not covered in the private sector, limiting risk stratification in early stage HR+/HER2- breast cancer. Previous studies have developed machine learning tools to predict the 21-gene recurrence score directly from quantitative immunohistochemistry results and clinical factors. We evaluated this approach in a Brazilian cohort to determine the ability to predict prognosis and guide chemotherapy decisions in a resource‑constrained setting without genomic testing. Patients and methods We retrospectively analyzed HR+/HER2- breast cancer patients (stage I-III, ≤3 positive nodes) treated at the Instituto Nacional de Cancer, in Brazil (INCA) from 2016 – 2018. Age, grade, histologic subtype, and quantitative ER, PR, and Ki-67 expression were used to predict the 21-gene recurrence score with the previously published machine learning tool. Patients were separated into low-risk group and a high-risk group using a predefined threshold that achieves 90% sensitivity for recurrence score > 25. Disease free interval (DFI) and overall survival (OS) were estimated by Kaplan-Meier curves; hazard ratios were derived from Cox models to determine the prognostic difference of the low / high risk groups. Results We identified a sample of 299 cases for this analysis, with an average age of 59. 92 (31%) were PR negative, 212 (70%) had tumor sizer ≥ 2 cm, 163 (55%) had Ki-67 expression of 20% or higher, and 181 (61%) received chemotherapy. Median follow‑up was 73 months (95% CI, 71-75). Using the 90% sensitivity threshold, 15.4% of patients were low risk. Recurrence rates were 2.2% in low‑risk versus 19.4% in high‑risk patients. Five‑years DFI at 90% sensitivity was significantly better for low‑risk versus high‑risk (97.4% vs. 81.8%; long-rank p=0.0054). No significant differences in 5‑year OS were observed. In multivariate analysis, stage III disease and Ki‑67 ≥ 20% were also independent predictors of recurrence. Although chemotherapy was not associated with a reduction in disease free interval in either group, the excellent outcomes in the low risk cohort with (recurrence rate 6.3%) or without (recurrent rate 0%) chemotherapy, suggest this subgroup can safely forgo such treatment without genomic testing. Conclusion This machine learning prognostic tool demonstrated strong prognostic performance in a Brazilian cohort of HR+/HER2- early stage breast cancer patients, identifying a low‑risk subgroup with excellent DFI and no apparent benefit from chemotherapy, and is available for use online (rsncdb.cri.uchicago.edu). These findings support its use for therapy de‑escalation when genomic assays are unavailable. Further prospective studies are required to validate these findings.

M. Li¹, V. Wong¹, S. Baron-Hay², R. de Boer³, F. Boyle⁴, A. Campbell¹, I. M. Collins⁵, K. Cuff⁶, L. Gately⁷, C. Georgiou⁸, S. Greenberg⁹, E. Jude¹⁰, B. Karki¹¹, K. Mok¹², C. Morton¹, L. Nott¹³, M. Nottage¹⁴, N. Rainey¹⁵, J. Torres¹⁶, I. Tung¹⁷, P. Gibbs¹, S. Lok¹; ¹Gibbs Lab, Walter Eliza Hall Institute of Medical Research, Victoria, AUSTRALIA, ²Medical Oncology, Northern Cancer Institute, New South Wales, AUSTRALIA, ³Medical Oncology, St Vincent’s Private Hospital, Victoria, AUSTRALIA, ⁴Medical Oncology, Mater North Sydney Hospital, New South Wales, AUSTRALIA, ⁵Medical Oncology, South West Healthcare, Victoria, AUSTRALIA, ⁶Medical Oncology, Princess Alexandra Hospital, Queensland, AUSTRALIA, ⁷Medical Oncology, Alfred Health, Victoria, AUSTRALIA, ⁸Medical Oncology, Bendigo Health, Victoria, AUSTRALIA, ⁹Medical Oncology, Western Health, Victoria, AUSTRALIA, ¹⁰Medical Oncology, Austin Health, Victoria, AUSTRALIA, ¹¹Medical Oncology, Toowoomba Hospital, Queensland, AUSTRALIA, ¹²Medical Oncology, Liverpool Hospital, New South Wales, AUSTRALIA, ¹³Medical Oncology, Royal Hobart Hospital, Tasmania, AUSTRALIA, ¹⁴Medical Oncology, Royal Brisbane and Women’s Hospital, Queensland, AUSTRALIA, ¹⁵Medical Oncology, Cairns Hospital, Queensland, AUSTRALIA, ¹⁶Medical Oncology, Goulburn Valley Health, Victoria, AUSTRALIA, ¹⁷Medical Oncology, Eastern Health, Victoria, AUSTRALIA.

BACKGROUND: The incorporation of cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) into first line (1L) systemic treatment for patients with HR+ ABC is now standard practice and leads to improved survival. However, there is a paucity of data on uptake of standard therapies and their associated toxicities in the real-world setting. Here, we present updated results from the ARORA registry. METHODS: ARORA is a secondary data use study of Australian patients aged ≥18 years and diagnosed with HR+ ABC after 1 Jan 2020. Prospective data is captured on patient characteristics, disease course, systemic therapy sequencing and treatment outcomes in routine clinical practice. Database lock for analysis was 19 May 2025. RESULTS: Data was analysed from 457 patients at 17 sites, with a median follow-up of 38.8 months. Median age was 64 years (24% ≥75 years). 65.6% were ECOG 0-1 and 2.8% had a BRCA1/2 pathogenic variant. 44.2% had liver or lung metastases, and 19% had bone-only disease. 60.4% had relapsed metastatic disease. Of these, 9.1% and 46.7% had received neoadjuvant and adjuvant chemotherapy respectively following early stage disease, and 75.2% had received adjuvant endocrine therapy (ET). 44.5% relapsed within 12 months of stopping adjuvant ET. 9 patients (2%) did not receive any systemic therapy for ABC. Of the 448 patients on 1L therapy, 335 (74.8%) received CDK4/6i + ET, 67 (15%) received ET alone and 41 (9.1%) received chemotherapy. Clinician preference for 1L CDK4/6i was palbociclib (32.6%), followed by ribociclib (27.2%) and abemaciclib (11.2%). Patients who received 1L ET alone were older (median 79 vs 63 years, 62.7% vs 18.5% ≥75 years), with poorer performance status (44.8% vs 8.7% ECOG ≥2) and more co-morbidities (29.8% vs 10.5% Charlson index ≥2). Conversely, those who received 1L chemotherapy were younger (median 58 years, 7.3% ≥75 years), with better performance status (46.3% vs 37.9% ECOG 0) and fewer co-morbidities (92.7% vs 88.9% Charlson index <2). They were more likely to have visceral metastases compared to those on CDK4/6i + ET (58.5% vs 45.7%), particularly liver metastases (46.3% vs 19.1%). Median 1L progression-free survival with 1L CDK4/6i + ET was 33.9 months, consistent with the upper end reported in trials (23.8–33.6 months). Common reported toxicities with CDK4/6i were diarrhoea (62.2% abemaciclib vs 10% ribociclib vs 6.6% palbociclib), neutropenia (44.9% palbociclib vs 40.8% ribociclib vs 22.2% abemaciclib) and nausea/vomiting (28.3% ribociclib vs 22.2% abemaciclib vs 17.6% palbociclib). Hepatotoxicity occurred in 5.8% ribociclib vs 4.6% abemaciclib vs 0.7% palbociclib. 2.5% of patients on ribociclib had QTc prolongation. Pneumonitis occurred in 1 patient on each CDK4/6i. Treatment was stopped due to toxicity for 20.5% ribociclib, 18% abemaciclib and 12.3% palbociclib. At the time of database lock, 117 of 335 patients (34.9%) who received 1L CDK4/6i + ET had moved to second line (2L). 60 (51.3%) received chemotherapy alone, 39 (33.3%) received ET alone and 5 (4.3%) received targeted therapies (e.g. mTOR or PIK3CA inhibitors). Capecitabine was the most common chemotherapy regimen (44/60, 73.3%). Median 2L duration of treatment was longest with targeted therapies (6.8 months), followed by chemotherapy (4.8 months) and ET alone (3.3 months). Overall survival data is immature. CONCLUSION: While CDK4/6i + ET is recommended as 1L treatment of HR+ ABC, three-quarters of routinely treated patients received this combination. A substantial minority received ET alone or chemotherapy. Age, ECOG, co-morbidity burden and presence of visceral disease remain major determinants of treatment choice. CDK4/6i toxicity profiles are consistent with trials. In 2L, chemotherapy is preferred in over half of patients, but clinical outcomes trend better if targeted therapies are available.

J. Singh¹, A. Kulkarni², F. Ehrich¹, C. White¹, Y. Chen¹, K. Alexander¹, A. Shahrokni¹, M. Robson¹, L. Norton¹, D. Lake¹; ¹Medicine, Memorial Sloan Kettering, New York, NY, ²Medicine, Columbia University Medical Center, New York, NY.

INTRODUCTION Approximately 15% cases of Triple Negative Breast Cancer (TNBC) are diagnosed in individuals over the age of 70. Older patients remain underrepresented in clinical trials. We conducted a retrospective review of patients to describe the clinical practice patterns and outcomes in patients aged ≥70 years with stage I-III TNBC who were treated at Memorial Sloan Kettering Cancer Center (MSKCC). MATERIAL AND METHODS Medical records of patients with patients aged ≥ 70 years diagnosed with stage I-III triple negative breast cancer from January 1^st, 2015, through December 31^st, 2019, were abstracted. Charts were analyzed for patient demographics, cancer stage, pathology reports, surgical and systemic therapy data. Chemotherapy (C) and non-chemotherapy (NC) groups were compared based on baseline characteristics, toxicities, and outcomes. We compared patient characteristics by chemotherapy type using Wilcoxon rank sum test, Pearson’s Chi-squared test, and Fisher’s exact test. Overall Survival (OS), Breast Cancer Specific Survival (BCSS), and Recurrence Free BCSS (RF-BCSS) were examined using Cox proportional hazards models. All statistical analyses were conducted using R. RESULTS Total 144 patients were included in our data analysis. The median age of participants was 75 years (range 70-96). The number of patients with stage I, II, and III disease was 61 (42%), 66 (46%), and 17 (12%), respectively. NC group was associated with older median age (81 years vs. 74 years (p<0.001)) and a higher rate of referral to geriatric medicine (31% in NC vs. 15% in C, p=0.045). The NC group had significantly higher difficulties in ADLs such as walking (27% vs. 12%, p=0.041), dressing (19% vs. 4.4%, p=0.014), and bathing (19% vs. 4.4%, p=0.014) compared to the C group. NC group also had significantly higher difficulties in IADLs such as meal preparation (27% vs. 3.3%, p0.9) and RF-BCSS (HR 0.68, 95% CI 0.34-1.37, p=0.3) between C- and NC- groups. Doxorubicin-Cyclophosphamide-Paclitaxel (ACT) and Cyclophosphamide-Methotrexate-5-Fluorouracil (CMF) were the most common chemotherapy regimens administered. Compared to ACT, CMF was associated with greater median age (median age 75 vs. 71 years, p0.9), BCSS (HR 1.26, 95% CI 0.40-3.97; p=0.7), and RF-BCSS (HR 1.25, 95% CI 0.44-3.51; p=0.7) in patients receiving ACT versus CMF. CONCLUSIONS In our single institutional experience, we observed that two-thirds of older patients with early-stage TNBC received systemic polychemotherapy. C-group had an improved OS but not BCSS and RF-BCSS, a finding likely driven by non-oncological factors, with NC being a frailer group of patients with other competing causes of mortality. ACT and CMF were the most common regimens used. Use of CMF was associated with age ≥75, stage I disease, ADL/IADL difficulties, and adjuvant setting. We observed no difference in survival outcomes between the two chemotherapy regimens. CMF remains an efficacious option and a potentially viable alternative to ACT in TNBC, especially in the setting of early stage and advanced age.

G. Carvalho¹, F. Rodrigues², P. Fernandes², I. Small¹, J. Silva¹, L. Araujo¹; ¹Clinical Research and Technological Development Division, Brazilian National Cancer Institute, Rio de Janeiro, BRAZIL, ²Pathology Department, Brazilian National Cancer Institute, Rio de Janeiro, BRAZIL.

Background This study assessed immunohistochemical (IHC) discordance between primary breast cancer (BC) and brain metastases (BCBM) in a Brazilian population. While 20-40% of BC patients develop BCBM, particularly those with HER2-positive or triple-negative subtypes, phenotypic changes may occur during disease progression, driven by tumor heterogeneity and alterations in the tumor microenvironment (TME). Due to the limited availability of BCBM samples, data on IHC discordance remain scarce. Methods This retrospective cohort study included women who underwent neurosurgical resection for BCBM between January 2015 and December 2022 at the Brazilian National Cancer Institute (INCA). Clinical and pathological data were extracted from medical records. IHC markers ─ estrogen receptor (ER), progesterone receptor (PR), HER2, and Ki67 ─ were assessed in BCBM samples and compared with the corresponding archival primary breast cancer specimens. An alluvial diagram was used to visually represent patterns of IHC discordance. The primary objective was to describe the frequency of IHC discordance between primary BC and corresponding BCBM. Secondary objectives included evaluation of associations between clinicopathological and sociodemographic features and IHC discordance, as well as its impact on survival outcomes. Results Among the 105 eligible patients, 64% (n = 67 patients) were Black or mixed-race, and 41% (n = 42) had not completed primary education. A significant proportion were obese (43%, n = 45), and 42% (n = 44) had hypertension. The mean age was 49 years (SD ±10), and 58% (n = 61) were premenopausal. Most tumors were ductal (87%, n = 92), and grade II (45%, n = 47) or grade III (46%, n = 48), with the HER2-positive subtype being the most frequent (48%, n = 51). Overall, 69% (n = 52) of patients had locally advanced disease, with a mean of 5 (SD ±6) affected lymph nodes. Among those who received neoadjuvant chemotherapy, 16% (n = 13) achieved a pathological complete response. About 14% (n = 15) presented with de novo metastatic disease. At the time of BCBM diagnosis, 91% (n = 95) exhibited neurological symptoms, most commonly headache (62%, n = 59) and dizziness (37%, n = 35). A single brain lesion was observed in 67% (n = 70) of cases. IHC discordance between primary BC and BCBM was found in 44% (n = 46) of patients, but this was not associated with differences in survival outcomes, including overall survival (OS) (p = 0.96), recurrence-free survival after BCBM diagnosis (post-BCBM RFS) (p = 0.81), or OS after BCBM diagnosis (post-BCBM OS) (p = 0.53). The most common phenotypic changes were loss of ER/PR expression (76%, n = 35) and enrichment of HER2 expression (15%, n = 7). Loss of ER/PR expression was not associated with post-BCBM risk of death (p = 0.52). Conclusion A notably high frequency of IHC discordance between primary breast tumors and brain metastases was observed in this real-world Brazilian study, exceeding rates previously reported in the literature. To our knowledge, this is the first Brazilian study to investigate IHC changes in this context, conducted in a population with a high proportion of Black and mixed-race individuals. These results underscore the biological heterogeneity of breast cancer in underrepresented populations and emphasize the need for more precise, individualized management strategies for patients with BCBM.

O. Serra¹, A. Farolfi¹, F. Merloni¹, C. Gianni¹, G. Miserocchi¹, N. Gentili¹, M. Mariotti¹, G. Di Menna¹, C. Casadei¹, F. Rusconi², A. Andalò¹, S. Sabbioni¹, A. Carlini¹, D. Montanari¹, M. Sirico¹, R. Maltoni¹, L. Cecconetto¹, S. Sarti¹, M. Palleschi¹, A. Musolino¹; ¹Medical Oncology, Breast & GYN Unit, IRST IRCCS Dino Amadori, Meldola, ITALY, ²TrineTX, TrineTX, Cambridge, MA, USA, MA.

Herpes Zoster Vaccination and Risk of Breast Cancer in Women Undergoing Mammographic Screening: A TriNetX Real-World AnalysisBackgroundHerpes Zoster vaccination is routinely recommended for adults aged ≥50 years to prevent shingles and its complications. To date, no evidence exists that herpes zoster vaccination reduces breast cancer (BC) risk. Observed associations between vaccinations and lower cancer incidence in some real-world studies may reflect differences in healthcare behavior, immune status, or unmeasured confounding rather than a true protective effect. We investigated whether vaccination with Shingrix®, a recombinant, adjuvanted herpes zoster vaccine, might influence the risk of subsequent BC diagnosis in women undergoing routine mammographic screening.MethodsWe performed a retrospective real-world study using the TriNetX Global Collaborative Network. We included women aged ≥50 years undergoing mammographic screening. The initial cohorts included 5,696 vaccinated women and 1,116,138 unvaccinated women. The vaccinated cohort comprised women who received Shingrix® after screening, while the unvaccinated cohort included women who underwent screening but were never vaccinated against herpes zoster. Patients with a prior diagnosis of BC before the observation period were excluded. Propensity score matching (PSM) was performed based on age, race, ethnicity, Charlson Comorbidity Index, BMI, smoking, alcohol-related disorders, genetic susceptibility to malignancy, and systemic corticosteroid use, resulting in 5,680 women per group. Additionally, multivariable Cox proportional hazards models were applied, adjusting for age, genetic susceptibility, and alcohol-related disorders, with a separate analysis restricting the unvaccinated group to academic medical centers. The observation period extended to 20 years in the TriNetX network. The outcome was the incidence of BC, analyzed as time-to-event from the index date of vaccination or screening.ResultsAfter matching, 5,680 vaccinated women were compared to an equal number of unvaccinated women. The cumulative incidence of BC was significantly lower among vaccinated patients, with 6.4% developing BC compared to 10.7% in the unvaccinated group (risk difference −4.2%, 95% CI −5.2% to −3.2%; p<0.001). Cox regression in the unmatched cohorts confirmed this association, yielding a hazard ratio of 0.617 (95% CI, 0.557–0.684; p<0.0001) when comparing vaccinated patients to the overall unvaccinated group. When restricting the analysis to unvaccinated women treated at academic centers, the association appeared even stronger, with a hazard ratio of 0.447 (95% CI, 0.404–0.496; p<0.0001). However, the absolute differences in incidence rates remained modest. ConclusionsIn this large real-world analysis, vaccination with Shingrix® was associated with a significantly reduced risk of BC diagnosis among women undergoing mammographic screening. However, the observed 40–45% risk reduction is difficult to explain biologically and may result from healthy user bias, residual confounding related to factors such as family history or hormonal therapy use, or surveillance bias leading to earlier detection in vaccinated women. These findings should be interpreted as hypothesis-generating and require confirmation in prospective studies.Keywordsbreast cancer, herpes zoster vaccination, Shingrix, real-world data, TriNetX, cancer risk, immunization, screening.

Y. Chen, J. Zhao, L. Ding, Q. Li, J. Chai, Y. Wang; Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China, Guangzhou, CHINA.

First Real-World Evidence Linking Anxiety to Poorer Treatment Response and Survival in Early-Stage Breast Cancer Introduction:Anxiety is a prevalent but often underrecognized comorbidity in breast cancer patients. Despite advances in systemic therapies that have improved the cure rates of early-stage disease, the psychological burden associated with diagnosis, treatment-related toxicity, and uncertainty about prognosis remains substantial. Emerging evidence suggests that anxiety may not only impair quality of life but also negatively impact treatment efficacy and survival. However, robust data on this association are lacking. This study represents the first large-scale, real-world investigation evaluating the impact of anxiety on pathological complete response (pCR) and disease-free survival (DFS) in early-stage breast cancer. The association between anxiety and pCR is reported here for the first time. Methods:In this single-center, real-world cohort study, 2,113 female patients with early-stage breast cancer treated between June 2023 and June 2025 were enrolled. Anxiety was assessed at baseline using the Zung Self-Rating Anxiety Scale (SAS), with scores ≥50 indicating clinically significant anxiety. Clinical and demographic data were collected, including tumor stage, treatment type, and reimbursement status. pCR was evaluated post-neoadjuvant therapy. DFS was defined as the interval from surgery to documented recurrence or last follow-up. Logistic regression and Cox proportional hazards models were used for multivariate analysis. Results:Of the 2,113 patients, 700 (33.1%) exhibited clinically significant anxiety, including 58 (8.3% of anxious patients) with severe anxiety. Higher anxiety prevalence was associated with age ≤50 years (P < 0.001), more advanced tumor stage (P < 0.001), and lower medical insurance coverage (P < 0.05). BMI, marital status, and socioeconomic status were not significantly correlated. Patients with anxiety had significantly lower pCR rates (OR = 2.58; 95% CI: 1.82-3.71; P < 0.001), a finding that remained significant after adjusting for potential confounders, including molecular subtype, tumor burden, and other clinical variables (adjusted OR = 2.83; 95% CI: 1.87-4.33; P < 0.001). In survival analysis, the median DFS was 36.7 months in the anxiety group vs. 50.0 months in the non-anxiety group (P < 0.001). Anxiety was an independent prognostic factor for inferior DFS in multivariate Cox regression (HR = 2.56; 95% CI: 1.51-4.32; P < 0.001). Conclusion:This real-world study provides the first evidence that anxiety is an independent predictor of both lower pCR rates and shorter DFS in early-stage breast cancer. These findings underscore the clinical importance of routine psychological screening and timely intervention. Addressing anxiety may not only improve patient well-being but also enhance treatment response and survival outcomes.

E. Rohr¹, T. Alotaibi², F. Moria³, N. Bouganim⁴; ¹Department of Internal Medicine, Faculty of Medicine and Health Sciences, McGill University, Montréal, QC, CANADA, ²Department of Medical Oncology, The Medical Services of the Ministry of Interior, Riyadh, SAUDI ARABIA, ³Faculty of Medicine, King Abdulaziz University, Jeddah, SAUDI ARABIA, ⁴Department of Medical Oncology, McGill University Health Centre, Montréal, QC, CANADA.

Background:Doxorubicin-cyclophosphamide (AC) has remained a cornerstone of breast cancer therapy for over four decades.^¹,² Despite its widespread use in clinical trials, long-term data and toxicity data remain limited in non-clinical trial patients. Chronic complications such as chemotherapy-induced cardiomyopathy (CIMP), defined by left ventricular dysfunction, and chemotherapy-induced leukemia carry important quality-of-life consequences.^4-6 In this study, we assessed the efficacy and toxicity of AC chemotherapy in a real-world cohort of breast cancer patients with a median follow-up of 8.1 years. Methods:We conducted a descriptive analysis of a prospectively maintained institutional database, including breast cancer patients treated with AC chemotherapy (doxorubicin 60 mg/m² and cyclophosphamide 600 mg/m²) in the adjuvant or neoadjuvant setting at the McGill University Health Centre from 2016 to 2025, with a median follow-up time of 8.1 years. Primary outcomes included metastatic recurrence (rate and site), all-cause mortality, cardiotoxicity, and hematological malignancies. Subgroup analyses were performed based on age, stage, and tumor subtype. Statistical analyses included descriptive statistics for baseline characteristics, Fisher’s exact tests for categorical comparisons, Kaplan-Meier estimates for survival outcomes, and multivariable Cox proportional hazards models. All analyses were conducted using R (v4.5.1). Results:A total of 98 patients were included in the final analysis. All patients were women, with a mean age of 60.7 ± 12.0 years. Most were diagnosed with invasive ductal carcinoma (87.8%) and had stage II disease (56.1%). No patients were lost to follow-up, with a median follow-up duration of 97 months. Excluding those with de novo metastatic disease (7 patients), recurrence occurred in 13 of 91 patients (14.3%), with a median time to recurrence of 40.1 months. Metastatic rates were significantly higher in stage III compared to stage I-II disease (42.1% vs. 6.9%, p < 0.001). No significant difference in recurrence was observed across tumor subtypes (p = 0.919). The most common metastatic sites were bone (84.6%) and liver (76.9%). Overall mortality was 18.4%, significantly higher in advanced-stage (stage III-IV) patients compared to early-stage (stage I-II) disease (50.0% vs. 6.9%, p < 0.001). Triple-negative breast cancer had the highest subtype-specific mortality (29.4%). Five-year overall survival was 88.7%, with advanced stage at diagnosis emerging as the only statistically significant independent predictor of mortality (HR 8.96, 95% CI 3.19-25.18; p < 0.001). The cardiotoxicity rate was 1.0%, with one patient developing CIMP-defined heart failure (LVEF 10-15%) and requiring coronary care unit admission. No secondary hematologic malignancies were observed. ConclusionThis eight-year, prospectively collected real-world dataset confirms outcomes reported in randomized clinical trials. The favourable long-term survival and low rates of metastasis, as well as an acceptable long-term safety profile, reinforce the use of doxorubicin-cyclophosphamide (AC) chemotherapy in high-risk patients. CIMP was an uncommon but important toxicity.

M. Palleschi¹, A. Farolfi¹, C. Gianni¹, G. Miserocchi¹, M. Corianò², N. Gentili¹, M. Mariotti¹, G. Di Menna¹, O. Serra¹, C. Casadei¹, F. Rusconi³, A. Andalò¹, S. Sabbioni¹, A. Carlini¹, D. Montanari¹, M. Sirico¹, R. Maltoni¹, L. Cecconetto¹, S. Sarti¹, F. Merloni¹, A. Musolino¹; ¹Medical Oncology, Breast & GYN Unit, IRST IRCCS Dino Amadori, Meldola, ITALY, ²Medical Oncology and Breast Unit,, Department of Medicine and Surgery, University Hospital of Parma, Parma, ITALY, ³TriNetX, LLC, TriNetX, Cambridge, MA.

Real-World Outcomes of Trastuzumab Deruxtecan with or without Endocrine Therapy in HER2-Low, Hormone Receptor-Positive Metastatic Breast Cancer: A Propensity-Matched AnalysisAuthors (max 50): 21Michela Palleschi^a, Alberto Farolfi^a, Caterina Gianni^a, Giulia Miserocchi^a, Matilde Corianò^b, Nicola Gentili^c, Marita Mariotti^a, Giandomenico Di Menna^a, Olga Serra^a, Chiara Casadei^a, Francesca Rusconi^d, Alice Andalò^c, Simone Sabbioni^a, Andrea Carlini^a, Daniela Montanari^a, Marianna Sirico^a, Roberta Maltoni^a, Lorenzo Cecconetto^a, Samanta Sarti^a, Filippo Merloni^a , Antonino Musolino^aAffiliation:a Medical Oncology, Breast & GYN Unit IRCCS Istituto Romagnolo per lo Studio Dei Tumori (IRST) “Dino Amadori”b Medical Oncology Unit, University Hospital of Parma, 43126 Parma, Italy.c Data Unit, IRCCS Istituto Romagnolo per lo studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italyd TriNetX, LLC, Cambridge, MA, USA Background:Combination therapy involving anastrozole or fulvestrant with fam-trastuzumab deruxtecan-nxki (TDX-d) has demonstrated promising antitumour activity in chemotherapy-naïve, HER2-low, hormone receptor-positive (HR+) metastatic breast cancer (mBC) patients, as evidenced by the phase 1b DESTINY-Breast08 trial (NCT04556773). Although this regimen is not currently established as a standard of care, it is being utilized in several oncology centers. However, real-world evidence supporting this strategy remains limited.Methods:Applying the TriNetX Global Collaborative Network, we retrospectively identified two cohorts comprising 658 mBC patients, stratified by receipt of TDX-d monotherapy or TDX-d in combination with endocrine therapy (ET). Propensity score matching (1:1) was performed to balance the cohorts (TDX-d plus ET, n=85; TDX-d alone, n=85) for age, race, and body mass index, all of whom had prior exposure to CDK4/6 inhibitors and chemotherapy. Hazard ratios (HRs) were calculated to compare overall survival (OS) between groups.Results:Following matching, the median age was 57.3 years (±13.9) in the TDX-d plus ET group and 56.7 years (±14.1) in the TDX-d monotherapy group. Median follow-up was 87.9 months for the combination cohort and 46.1 months for the monotherapy cohort. The combination group demonstrated a trend towards improved overall survival compared to TDX-d alone (HR=0.79; 95% CI, 0.465-1.344; p=0.384), although statistical significance was not achieved.Conclusions:This represents the first large-scale real-world cohort analysis evaluating the addition of endocrine therapy to TDX-d in patients with HER2-low, HR+ mBC. While these preliminary findings suggest a potential survival benefit with the combination approach, the limited follow-up duration preclude definitive conclusions. Further prospective studies are warranted to elucidate the clinical utility of combining TDX-d with ET in this patient population. Our research aims to perform ongoing follow-up of these patients to generate more robust data, thereby further clarifying the clinical benefit of combining TDX-d with ET in this population.Key-words (max 5): Trastuzumab deruxtecan; metastatic breast cancer; endocrine therapies; TrineTX; real world evidence

C. Chen¹, A. Ghosh², R. Potluri³; ¹Oncology Outcomes Research, AstraZeneca, Gaithersburg, MD, ²-, Putnam Associates, Gurugram, INDIA, ³-, Putnam Associates, New York, NY.

Background Cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) + aromatase inhibitor (AI) is the current standard of care for first-line (1L) treatment of hormone receptor (HR)+/human epidermal growth factor receptor (HER2−) advanced breast cancer (ABC). However, treatment resistance is common and affects 1L treatment duration, which may lead to higher healthcare expenditure due to disease progression and health deterioration. To better understand the association between medical costs and the duration of 1L treatment, this study investigated the real-world costs and healthcare resource utilization (HCRU) for patients with ABC who received 1L CDK4/6i + AI, stratified by the duration of 1L treatment (DoT). Methods This retrospective, observational cohort study extracted data from a large US claims database for commercially insured and Medicare Advantage patients diagnosed with ABC between April 2017 and August 2024. Eligible patients received CDK4/6i + AI as 1L treatment and had a follow-up of ≥6 months (m). Patients were grouped into two cohorts: ≤12 m DoT and >12 m DoT until cessation of both CDK4/6i + AI. Baseline characteristics were summarized using descriptive statistics. For patients with ≥12 m of follow-up (or less if due to death), medical costs and HCRU for the first 12 m from the start of 1L treatment were captured and calculated per patient per month (PPPM). Generalized linear models were used to analyze the relationship between DoT and medical costs/HCRU, adjusting for age, year of ABC diagnosis, comorbidities, and insurance type. Cumulative medical costs per patient were calculated in monthly intervals for the total study population according to DoT, from the start of 1L treatment to a maximum of 24 m. Results Among the 6464 patients in the study sample (mean age: 60.9 years, 65.0% commercially insured), 4546 had ≥12 m of follow-up (or less if due to death). Compared to patients with DoT >12 m (n=3830), those with DoT of ≤12 m (n=716) had higher mean PPPM costs ($6,424 vs $3,645, p12 m versus DoT ≤12 m at 12 m of follow-up, and $46,479 lower at 24 m of follow-up. Key factors driving the medical cost savings in patients with DoT >12 m included reduced inpatient/outpatient care and fewer office visits. Conclusions Longer duration of 1L treatment was associated with reduced HCRU and substantial medical cost savings. Adoption of treatment approaches that prolong 1L DoT could meaningfully reduce the economic burden of cancer care. Table. Medical costs and HCRU for patients, based on the duration of 1L treatment

V. Castagnaviz¹, S. P. Gampenrieder¹, A. Pichler², W. Herz³, R. Pusch⁴, C. Dormann⁴, C. Suppan⁵, M. Sandholzer⁶, T. Winder⁶, S. Heibl⁷, L. Scagnetti⁷, C. Schmitt⁸, A. F. Zabernigg⁹, D. Egle¹⁰, C. Hager¹¹, P. Pichler¹², F. Roitner¹³, J. Andel¹⁴, K. Strasser-Weippl¹⁵, R. Bartsch¹⁶, M. Hubalek¹⁷, M. Knauer¹⁸, C. F. Singer¹⁹, G. Rinnerthaler⁵, R. Greil²⁰; ¹Department of Internal Medicine III, Paracelsus Medical University Salzburg, Salzburg, AUSTRIA, ²Internal Medicine – Department for Haemato-Oncology, LKH Hochsteiermark, Leoben, AUSTRIA, ³Department of Surgery, Breast Health Center, LKH Hochsteiermark, Leoben, AUSTRIA, ⁴Internal Medicine I, Ordensklinikum Linz Barmherzige Schwestern – Elisabethinen, Linz, AUSTRIA, ⁵Division of Oncology, Department for Internal Medicine, Medical University Graz, Graz, AUSTRIA, ⁶Department of Internal Medicine II, Academic Teaching Hospital Feldkirch, Feldkirch, AUSTRIA, ⁷Department of Internal Medicine IV, Klinikum Wels-Grieskirchen GmbH, Wels, AUSTRIA, ⁸Department for haematology and internal oncology, Kepler University Hospital Linz, Linz, AUSTRIA, ⁹Department of Internal Medicine, County Hospital Kufstein, Kufstein, AUSTRIA, ¹⁰Department of Gynaecology, Medical University Innsbruck, Innsbruck, AUSTRIA, ¹¹Breast Center, Breast Center Dornbirn, Dornbirn, AUSTRIA, ¹²Department for Internal Medicine 1, University Hospital St.Pölten, St. Pölten, AUSTRIA, ¹³Department of Internal Medicine II, Hospital Braunau, Braunau am Inn, AUSTRIA, ¹⁴Department of Internal Medicine II, Pyhrn-Eisenwurzen Klinikum Steyr, Steyr, AUSTRIA, ¹⁵Department of Medicine I, Clinic Ottakring, Vienna, AUSTRIA, ¹⁶Department of Medicine I, Division of Oncology, Medical University of Vienna, Vienna, AUSTRIA, ¹⁷Department of Gynaecology, Breast Health Center Schwaz, Schwaz, AUSTRIA, ¹⁸Breast Center, Tumor and Breast Center Eastern Switzerland, St. Gallen, SWITZERLAND, ¹⁹Department of Obstetrics and Gynecology and Comprehensive Cancer Center, Medical University of Vienna, Vienna, AUSTRIA, ²⁰Austrian Group Medical Tumor Therapy, AGMT gemeinnützige GmbH, Vienna, AUSTRIA.

Background: Second primary tumors (SPTs) occur in approximately 10% of patients following an initial cancer diagnosis and are associated with increased cancer-related mortality. Ongoing advancements in systemic therapies have led to a growing population of both breast cancer (BC) survivors and patients living with metastatic disease. Consequently, individuals with BC face a heightened risk of developing SPTs and second primary breast cancers (SPBC), with a reported 25-year cumulative incidence of contralateral BC of about 10%. Here we present real-world data on SPTs and SPBC in patients with metastatic breast cancer (MBC) derived from the Austrian Study Group of Medical Tumor Therapy (AGMT) MBC-Registry. Patients and methods: The AGMT_MBC-Registry is a multicenter, nationwide, ongoing retrospective and prospective registry capturing data from MBC patients across Austria. For this analysis, only patients with documented information on the presence or absence of SPTs were included. The analysis of SPBC was limited to patients with known tumor location and diagnosis date. To avoid misclassification, no distinction was made between local recurrences and ipsilateral SPBC. Bilateral BC was defined as cancer diagnosed in both breasts within 90 days. Results: As of June 26, 2024, the AGMT_MBC-Registry included 2,850 patients. Among 2,630 evaluable patients, 225 (8.6%) were diagnosed with a SPT, with 12% (27/225) of these having more than one SPT. Most SPTs were diagnosed after the initial BC diagnosis but prior to the development of metastatic disease. A total of 260 malignancies were reported: 88% were solid tumors and 12% hematologic. The most frequent solid tumors were colorectal cancer, melanoma, and lung cancer, while non-Hodgkin lymphoma and acute leukemia were the most common hematologic malignancies (Table 1). Among 2,576 evaluable patients, 533 (20.7%) experienced a SPBC: 145/533 (27.2%) contralateral, 287/533 (53.8%) ipsilateral, and 101/533 (18.9%) initially presented with bilateral BC. Conclusion: In this real-world analysis of patients with MBC, 9% were diagnosed with SPT and 21% experienced a SPBC. These findings highlight the critical role of histopathological verification of suspicious lesions and metastases and underscore the importance of continued awareness for SPTs – not only among BC survivors but also in patients with metastatic disease Table 1:

C. Gullotta¹, S. Cobo¹, B. Walbaum¹, M. Bergamino¹, R. Gómez-Bravo¹, O. Martínez-Sáez¹, F. Schettini¹, E. Segui¹, I. García-Fructuoso¹, T. Pascual¹, N. Chic¹, M. González-Rodríguez¹, G. Riu², E. Carcelero², A. Rodríguez-Hernández¹, E. Sanfeliu³, P. Galván¹, M. Muñoz¹, M. Vidal¹, A. Prat¹, F. Braso-Maristany¹, B. Adamo¹; ¹IDIBAPS, Hospital Clinic Barcelona, Barcelona, SPAIN, ²Department of Pharmacy, Hospital Clinic Barcelona, Barcelona, SPAIN, ³Pathology Department, Hospital Clinic Barcelona, Barcelona, SPAIN.

Title: Impact of prior treatment exposure and clinical-pathological factors on response and survival with sacituzumab-govitecan in advanced breast cancer: a consecutive real-world series Background: Sacituzumab govitecan (SG) is an antibody-drug conjugate (ADC) approved for the treatment of advanced triple negative (TNBC) and estrogen receptor positive-HER2 negative (ER+/HER2-) breast cancer (BC). Real-world data on response determinants are limited. We evaluated clinical-pathological factors associated with objective response rate (ORR), progression-free survival (PFS), and overall survival (OS) in a consecutive patient series treated in routine practice. Methods: This retrospective study included 74 consecutive female patients treated with SG at the Hospital Clinic of Barcelona between April 2022-April 2025. Clinical-pathological variables included tumor subtype, ECOG status, number of metastatic sites, visceral metastases, prior therapies, and Ki-67 index (pre-treatment or most recent metastatic biopsy). No patients had received prior ADC containing a TOP1 inhibitor payload. ORR was assessed radiologically according to RECIST version 1.1. ORR associations were tested by univariate logistic regression; survival by Kaplan-Meier and Cox models. Results: Median age was 57 years; 41 patients (54.9%) had TNBC and 33 (45.1%) ER+/HER2- BC. 61 patients had visceral disease (86%), 10 patients had brain metastasis (14%), 42 were ECOG status>1 (59.2%), and 43 had >3 metastatic sites (60.6%). The median number of previous chemotherapy lines in metastatic setting was 2. The ORR was 34.3% (2.9% complete and 31.4% partial). Stable disease and progressive disease occurred in 22.9% and 42.8%, respectively. ORR was 44.4% among the 31 patients who had received fewer than three prior lines of chemotherapy, compared to 27.9% in the 43 patients treated in the third-line setting or beyond. In univariate logistic regression, having received ≥3 chemotherapy lines, compared to 3 metastatic sites (HR=1.77, p=0.048) were independently associated with shorter PFS. No statistically significant associations were observed between PFS and Ki-67 (p=0.650). TNBC subtype (HR=4.46, p=0.006), visceral disease (HR=7.85, p=0.046), and ECOG status > 1 (HR=10.17, p<0.001) predicted for shorter OS. In contrast, ER+/HER2- (HR=0.24, p=0.010) and prior endocrine therapy (HR=0.32, p=0.004) were associated with longer OS. No statistically significant associations were observed between OS and Ki-67 index (p=0.153). Conclusions: In this real-world cohort, SG demonstrated limited antitumor activity across both TNBC and ER+/HER2- breast cancer. Clinical benefits were greater in patients with limited prior treatment exposure, preserved ECOG status, and lower disease burden. These findings support the earlier use of SG.

N. Stonebanks Cuillerier¹, H. Almarzooqi², V. Villareal-Corpuz¹, S. Saboobheh², I. Prakash², M. Basik², J. Boileau², K. Martel², S. Meterissian², M. Pollak³, S. M. Wong²; ¹Stroll Cancer Prevention Centre, Jewish General Hospital, Montreal, QC, CANADA, ²Department of Surgery, McGill University, Montreal, QC, CANADA, ³Department of Oncology, McGill University, Montreal, QC, CANADA.

INTRODUCTION: Endocrine prevention is a well-established preventative strategy for women with high-risk lesions (HRL). The objective of the study was to evaluate trends and factors associated with endocrine prevention adherence in this patient population. METHODS: We performed a retrospective cohort study of all women referred for high-risk evaluation due to diagnosed atypical ductal hyperplasia (ADH), atypical lobular hyperplasia (ALH), and lobular carcinoma in situ (LCIS) between 2019-2025. Data pertaining to eligibility, initiation, and adherence to endocrine prevention were extracted from the medical record. Univariate analyses were performed using Chi-squared and Fisher’s exact test to evaluate factors associated with adherence. RESULTS: Of 216 female HRL patients 188 met criteria and were included in the analytic cohort including 107 (56.9%) with ADH, 66 (35.1%) with ALH, and 15 (8%) with LCIS. The median age was 55 years (interquartile range [IQR]: 50-62). Overall, 106 (56.4%) HRL patients accepted a prescription of endocrine prevention. Low-dose tamoxifen was the most common regimen prescribed (64.2%), compared to regular dose tamoxifen (11.3%), raloxifene (19.8%), and anastrozole (4.7%). At a median follow up of 28 months (IQR 11-46 months), 71 women (67% of those who accepted a prescription) initiated endocrine prevention and 65 (61.3%) remained adherent. Lack of prior hormone replacement therapy use (65.6% vs 30.8%, p=0.02) and family history of breast cancer (77.8% vs 55.7%, p=0.04) were significantly associated with adherence to endocrine prevention. Adherence was not significantly different by regimen prescribed (p=0.66), nor was it significantly associated with age (p=0.08) or prior surgical excision of their HRL (p=0.52). Of the 42 patients who initiated tamoxifen 5 mg, 39 (92.9%) remained adherent during follow up, and of 12 women (23%) who had completed at least 3 years of therapy, 10 (83.3%) elected to continue or complete a total 5-year course of low dose tamoxifen.CONCLUSION: Adherence to endocrine prevention is high in women who initiate medication with few discontinuing due to side effects. Many women who initiate low dose tamoxifen remain adherent, with some electing to continue the regimen for 5 years total.

N. P. McAndrew¹, E. T. Corcoran², S. Alkassis¹, S. Franch-Expósito², K. Roche², S. Islam², C. Igartua², J. Mercer², P. A. Fields², A. Bardia¹, E. Cohen²; ¹Medicine (Hematology/Oncology), UCLA, Santa Monica, CA, ²AI, Tempus AI, Chicago, IL.

Background: Hormone receptor-positive (HR+) human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC) represents a significant clinical challenge with evolving treatment strategies. Cyclin-dependent Kinase 4/6 inhibitors (CDK4/6i) and taxanes are commonly used to treat HR+ HER2- mBC. This study investigates the impact of first- and second-line therapy selections on real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) in patients with HR+ HER2- mBC. Methods: The study cohort included 13,064 patients with HR+ HER2- mBC from the de-identified Tempus real-world multimodal database who received either first- (1L) or second-line (2L) CDK4/6i, taxane, or other therapy. Kaplan-Meier survival analysis and multivariate Cox regression accounting for main epidemiological confounding variables (age at diagnosis, presence of visceral metastases, and recurrent vs. de novo treatment status) were used to assess rwPFS and rwOS. Progression events included death, noted progression event or initiation of a new line of therapy. DNA sequencing data from the Tempus xT assay were analyzed to evaluate mutation landscapes and genetic alterations associated with different treatment sequences. Results: Patients with HR+ HER2- mBC (N = 13,046) who received 1L CDK4/6i + endocrine therapy (ET) had significantly improved rwPFS and rwOS relative to those receiving a taxane. We observed a trend towards faster progression in patients who received taxane as a 2L treatment after 1L CDK4/6i as opposed to other treatments (HR=1.33, P=0.052). Of patients who received 1L CDK4/6i, 2L rwPFS was longest in patients who were re-challenged with CDK4/6i (predominantly Palbociclib+Letrozole to Palbociclib+Fulvestrant). Patients who received 2L CDK4/6i following 1L taxane had longer 2L rwPFS than those who received a non-CDK4/6i 2L treatment (median PFS=5.9 months 2L CDK4/6i vs 3.6mo non-CDK4/6i). Across all patients who received 2L CDK4/6i, there was a trend toward better 2L rwPFS for those with 1L taxane compared to those who received 1L CDK4/6i (median PFS 5.9 mo vs median PFS=5.1mo). This result of best 2L response in patients receiving CDK4/6i following taxane in 1L remains consistent when fitting a multivariate model including treatment order, age at diagnosis, presence of visceral metastases, treatment recurrence, and prevalent mutations (BRCA, RB1, FGFR2, AKT1, ESR1, PIK3 (HR=0.80, p=0.109). Conclusion: This study demonstrates that the sequence of taxane and CDK4/6i treatments might impact survival outcomes in patients with HR+ HER2- mBC. While CDK4/6i+ET outperforms taxane in 1L, the findings suggest that taxane may cause sensitization to CDK4/6i, conferring better survival outcomes in a subset of patients where 1L taxane is advised, or a potential advantage to chemo before CDK4/6i re-challenge. These results need validation in additional datasets and underscore the importance of treatment sequencing in optimizing clinical outcomes for patients with HR+ mBC. Note: NPM and ETC contributed equally to this work

A. Brufsky¹, N. Iyengar², X. Liu³, B. Li⁴, D. Makari³, L. McRoy³, A. Cohen⁵, M. Estevez⁶, V. Abramson⁷, R. Layman⁸, G. Curigliano⁹; ¹Division of Hematology/Oncology, Department of Medicine, UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA, ²Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, ³US Oncology Medical Affairs, Pfizer Inc., New York, NY, ⁴Global Biometrics & Data Management, Pfizer Inc., New York, NY, ⁵Research Oncology, Flatiron Health Inc., New York, NY, ⁶Research Sciences, Flatiron Health Inc., New York, NY, ⁷Division of Hematology/Oncology, Vanderbilt University Medical Center, Nashville, TN, ⁸Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, ⁹Department of Oncology and Hemato-Oncology, University of Milano, European Institute of Oncology, IRCCS, Milano, ITALY.

Background A cyclin-dependent kinase 4/6 inhibitor (CDK4/6i) combined with endocrine therapy (ET) has been the standard of care (SOC) as first-line (1L) treatment for hormone receptor-positive/HER2-negative (HR+/HER2−) MBC for the past decade. Palbociclib (PAL), the first CDK4/6i approved, received accelerated US approval in 2015 for HR+/HER2− MBC based on its demonstrated efficacy and safety profile. An increasing number of real-world (RW) studies have shown that 1L PAL+ET significantly improves progression-free survival, tumor response, and overall survival (OS) compared with ET alone across diverse HR+/HER2− MBC populations. Overweight and obesity are common conditions associated with an increased risk of breast cancer and can influence cancer treatment outcomes. However, little is known about the effectiveness of CDK4/6i+ET, specifically in patients (pts) with HR+/HER2− MBC who are overweight/obese in routine US clinical practice. Methods This was a retrospective analysis of deidentified longitudinal data from the Flatiron Health Research Database. Pts were included if they were overweight or obese (BMI ≥25 kg/m²), had HR+/HER2− MBC, and initiated 1L PAL+AI or AI between Feb 2015−Jul 2024. OS was defined as the number of months from start of PAL+AI or AI alone to death. Date of death was a consensus mortality endpoint based on electric health records, Social Security Death Index, and obituary data, validated against the National Death Index. Pts were retrospectively followed until death, last medical activity, or January 2025 (data cut-off), whichever came first. Stabilized inverse probability of treatment weighting (sIPTW) was used to balance pt characteristics. Cox proportional hazards models were used to estimate the relative effectiveness of PAL+AI vs AI alone. Results A total of 8076 pts were eligible for analysis, including 5009 (62.0%) treated with PAL+AI and 3067 (38.0%) treated with AI alone. Compared with AI-alone pts, those treated with PAL+AI were younger and more likely to have ≥2 metastatic sites and lung/liver involvement but less likely to have ECOG score ≥2. After sIPTW, pt characteristics were generally balanced. Unadjusted median OS (95% confidence interval [CI]) was 51.4 (49.3-53.4) months with PAL+AI and 41.1 (38.9-43.3) months with AI (hazard ratio [HR]= 0.75 (0.71-0.80), P<0.0001). After sIPTW, median OS (95% CI) was 50.7 (48.7-53.1) months with PAL+AI and 42.4 (39.8-44.7) months with AI (HR=0.79 [0.74-0.85], P<0.0001). Consistent results were observed with 1:1 propensity score matching as a sensitivity analysis. See Table for baseline pt characteristics and OS results. Conclusions Compared with AI alone, PAL+AI is associated with improved OS in pts with HR+/HER2- MBC who are overweight/obese in US real-world setting, supporting 1L PAL+AI as a SOC for pts with HR+/HER2- MBC who are overweight/obese.

L. Brock¹, K. Freeman², A. A. Ashley McCook-Veal³, A. Labatut⁴, L. Lei⁵, S. Selimovic⁶, J. M. Switchenko⁷, N. A. Giordano⁶, M. Bhave⁸; ¹Medical Oncology, Winship Cancer Institute at Emory University and Nell Hodgson Woodruff School of Nursing, Atlanta, GA, ²Medical Oncology, Winship Cancer Institute at Emory University, Atlanta, GA, ³Biostatistics Shared Resource, Winship Cancer Institute at Emory University, Atlanta, GA, ⁴Oncology Clinical Pharmacy – Breast, Winship Cancer Institute at Emory University, Atlanta, GA, ⁵Hematology and Medical Oncology, Emory University – School of Medicine, Atlanta, GA, ⁶Nell Hodgson Woodruff School of Nursing, Emory University, Atlanta, GA, ⁷Biostatistics & Bioinformatics, Rollins School of Public Health and Winship Cancer Institute at Emory University, Atlanta, GA, ⁸Hematology and Medical Oncology, Winship Cancer Institute at Emory University, Atlanta, GA.

Background: Pembrolizumab is used with neoadjuvant chemotherapy in high-risk early-stage triple-negative breast cancer (TNBC).¹ Results from the 2021, KEYNOTE-522 trial (KN-522) show improved pathological complete response (pCR) and event-free survival (EFS).^1,2 Although TNBC accounts for ~15% of breast cancers, African American (AA) women experience higher incidence and worse outcomes than Non-Hispanic White women (NHW).^3,4 Despite this, AA representation in immunotherapy clinical trials for breast cancer (e.g., KEYNOTE-522, IMPASSION-130, KEYNOTE-355) was <6%^1,5,6, highlighting the need for real-world evaluations of treatment outcomes across racial groups. This retrospective study examines real-world toxicities and treatment outcomes of pembrolizumab combined with neoadjuvant chemotherapy in early-stage (I-III) TNBC, based on the KN-522 regimen, with a focus on racial differences between AA and NHW patients. Methods: We abstracted data from early-stage TNBC patients treated with the KN-522 regimen between 2021 and 2024 from an academic comprehensive cancer center. Descriptive analyses were conducted to compare clinical and safety outcomes among AA and NHW patients using ANOVA, Chi-square, or Fisher’s exact tests.⁷ Univariate and multivariable models evaluated associations between race and toxicity/treatment outcomes. Results: A total of 124 patients were identified: 80 Black (64.5%) and 44 NHW (35.5%), with a median age of 56.5 years (IQR: 42.5-66). Most had T2 tumors (54%), high-grade histology (84.6%), and at least one comorbidity (66.1%). Fifty percent achieved a pCR, while 5.6% experienced disease progression on KN-522, and 8.9% had local/distant recurrence. Significant racial differences were observed in age at treatment initiation (median: 59 years for AA vs. 51.5 years for NHW; p=0.018), BMI (mean: 32.2 vs. 29.1; p=0.026), and marital status (p<0.003). A higher proportion of NHW patients experienced anxiety (31.8% vs. 7.5%; p<0.001) and thyroid disorders (22.7% vs. 7.5%), while hypertension was more common in AA patients (57.5% vs. 29.5%; p=0.003). AA patients had a greater proportion of high-grade tumors (63.4% vs. 36.5%; p=0.576) and HER2-low expression (67.2% vs. 32.7%; p=0.233). pCR was achieved more among AA compared to NHW patients (65% vs. 35%). Although there were no statistically significant differences in overall outcomes across treatment or immune-related adverse events (irAEs), AA patients more frequently experienced treatment-related toxicities, including anemia (63.4% vs. 36.3%), grade 3/4 neutropenia (41.2% vs. 31.8%), and chemotherapy-induced peripheral neuropathy (60% vs. 43.1%). Additionally, treatment modifications related to the KN-522 regimen (p=0.965) and pembrolizumab (p=0.528) were more common among AA patients at 64.3% and 70.9% compared to 35.6% and 29.0% among NHW patients, respectively. Progression-free survival did not significantly differ between AA and NHW patients (p = 0.7562). Both groups exhibited high PFS rates at 12, 24, and 36 months. At 36 months post-treatment, overall survival probabilities for AA patients were 89.7% (95% CI: 76.6%-95.6%) and 97.3% (95% CI: 82.3%-99.6%) among NHW patients. Conclusion: This real-world analysis revealed that AA patients receiving KN-522 experienced higher rates of treatment-related toxicities, irAEs, and regimen modifications compared to NHW patients. Despite this, treatment effectiveness was comparable. These findings underscore the need for larger studies to validate outcomes and investigate factors influencing racial differences in treatment response.

A. Pomeranc, N. Chukwuma, E. Crewe, C. Courtney, J. Din, W. Hodgson, R. Binoy, P. Mone, S. Shrestha, R. Smith, S. Butt, A. Chung, O. Cornwall, M. Aboulela, Z. Campbell, S. McGrath, S. Redana, A. Ring, S. Johnston, N. M. Battisti; Medical Oncology, Royal Marsden Hospital, London, UNITED KINGDOM.

Background: Ribociclib is approved in combination with an aromatase inhibitor (AI) or fulvestrant for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer, and more recently has been approved as an adjuvant treatment in combination with an AI for patients with HR-positive, HER2-negative early breast cancer at higher risk of recurrence. Therefore, evaluating its safety in a less selected patient population in the real world is key. We aimed to evaluate it in patients treated at our Institution. Methods: We retrospectively identified patients with HR-positive, HER2-negative breast cancer who received Ribociclib between December 2017 and February 2024 at our institution. Demographics, disease characteristics, blood tests and toxicities were recorded for 90 patients. Simple statistics were used as appropriate. Results: Ninety patients were included in the analysis with a median age of 58 years (range: 30-86). Out of these, 27 (24.3%) were <50 years old and 50 (55.6%) were white, 78 (92.9%) had an ECOG performance status of 0-1 and 26 (29.2%) were premenopausal. Thirteen patients (14.4%) were receiving Ribociclib in the adjuvant setting, while 77 (85.5%) with palliative intent. Out of those with advanced disease, 46 patients (59.7%) had visceral metastases and 74 (96.1%) bony metastases. Forty-five (54.2%) had grade 3 tumours. Among patients with complete safety data, 72 (82.8%) had any grade of neutropenia (grade 3-4 in 48 [55.2%]), thirty-one (36.0%) had any grade of deranged liver function (grade 3-4 in 7 [8.1%]), 40 (45.5%) had any grade of anaemia, 20 (22.7%) had any grade of nausea, 30 (34.0%) had any grade of fatigue, 13 (14.7%) had any grade of skin rash and 1 (1.1%) had any grade of interstitial lung disease; seven patients (9.1%) had QTc prolongation (grade 1 in all patients). Ribociclib was dose reduced in 35 patients (41.7%) and discontinued in 54 patients (62.8%): due to progression in 33 (61.1%), hepatotoxicity in 4 (7.4%), haematological toxicity in 3 (5.6%) and patient preference in 2 (3.7%). Conclusions: Our analysis of the safety profile of ribociclib in this population confirms a similar neutropenia and dose reduction rate compared with published trials findings. However, rates of anaemia and deranged liver function were higher in our patient population. These findings are key to inform decision-making in a less selected patient population in the real world, especially ahead of the increasing use of ribociclib in the curative setting.

J. Żubrowska¹, M. Kubeczko², M. Pieniążek³, A. Polakiewicz-Gilowska², I. Kolářová⁴, M. Malejčíková⁵, L. Rusinova⁶, M. Holánek⁷, R. Soumarová⁸, K. Winsko-Szczęsnowicz⁹, A. Konieczna¹⁰, A. Młodzińska¹⁰, D. Krejčí¹¹, I. Danielewicz¹², M. Szymanik-Resko¹², T. Ciszewski¹³, M. Lisik-Habib¹⁴, A. Pękala¹⁴, H. Študentová¹⁵, J. Šustr¹⁶, A. Rudzińska¹⁷, B. Czartoryska-Arłukowicz⁹, A. Łacko³, M. Jarząb², R. Pacholczak-Madej¹⁸, Z. Bielčiková¹⁹, M. Püsküllüoğlu²⁰; ¹Department of Clinical Oncology, Holy Cross Cancer Center, Kielce, POLAND, ²Breast Cancer Center, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice, POLAND, ³1. Department of Oncology 2. Breast Unit Clinical Oncology Day Care Department, 1. Wrocław Medical University, 2. Lower Silesian Comprehensive Cancer Center, Wrocław, POLAND, ⁴Department of Oncology and Radiotherapy, Faculty of Medicine in Hradec Kralove and University Hospital in Hradec Kralove, Charles University, Hradec Králové, CZECH REPUBLIC, ⁵Oncology Clinic of LFUK, National Cancer Institute, Bratislava, SLOVAKIA, ⁶Department of Oncology, Stefan Kukura Hospital Michalovce, Michalovce, SLOVAKIA, ⁷Department of Comprehensive Cancer Care, Faculty of Medicine, Masaryk University, and Masaryk Memorial Cancer Institute, Brno, CZECH REPUBLIC, ⁸Department of Oncology, Third Faculty of Medicine, Charles University, University Hospital Kralovske Vinohrady, Prague, CZECH REPUBLIC, ⁹Department of Clinical Oncology, M. Skłodowska-Curie Bialystok Oncology Center, Białystok, POLAND, ¹⁰Department of Breast Cancer and Reconstructive Surgery, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, POLAND, ¹¹Department of Oncology, First Faculty of Medicine, Charles University in Prague, and Bulovka University Hospital, Prague, CZECH REPUBLIC, ¹²Oddział Onkologii i Radioterapii, Szpitale Pomorskie sp. z o.o., Gdynia, POLAND, ¹³Department of Metabolic Diseases and Immuno-oncology, Medical University of Lublin, Lublin, POLAND, ¹⁴Department of Proliferative Diseases, Nicolaus Copernicus Multidisciplinary Centre for Oncology and Traumatology, Lodz, POLAND, ¹⁵Department of Oncology, Faculty of Medicine and Dentistry, Palacky University and University Hospital, Olomouc, CZECH REPUBLIC, ¹⁶Department of Oncology and Radiotherapy, Faculty of Medicine in Pilsen, Charles University, and University Hospital Pilsen, Plzen, CZECH REPUBLIC, ¹⁷Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Kraków, POLAND, ¹⁸Department of Gynecological Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, POLAND, ¹⁹Department of Oncology, First Faculty of Medicine, Charles University, and General University Hospital, Prague, CZECH REPUBLIC, ²⁰Department of Clinical Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, Krakow, POLAND.

Background Patients with metastatic triple-negative breast cancer (mTNBC) and brain metastases (BM) constitute a subgroup with poor prognosis and limited treatment options. In the pivotal ASCENT trial, sacituzumab govitecan (SG) demonstrated clinical benefit in pretreated patients with mTNBC. An exploratory subgroup analysis of ASCENT trial included 61 patients with radiologically stable BM (32 in the SG arm), showing a modest improvement in progression-free survival (PFS) with SG versus chemotherapy (2.8 vs. 1.6 months), but no overall survival (OS) advantage (6.8 vs. 7.5 months). While suggestive of intracranial activity, these findings were derived from a small, highly selected population. Given the limited evidence in this setting, we aimed to evaluate the effectiveness and safety of SG in a real-world cohort of patients with active or treated BM Materials and Methods This retrospective multicenter study included female patients with mTNBC and radiologically confirmed BM who initiated SG between August 2021 and May 2025 across 13 oncology centers in the Czech Republic, Poland and Slovakia. Clinical data were extracted from patients’ medical records. Collected variables included baseline characteristics, number and size of BM lesions, prior neurosurgical resection, use and timing of central nervous system (CNS)-directed radiotherapy, treatment response, and adverse events (AEs) (graded per CTCAE v5.0). Radiologic responses were assessed using RECIST 1.1. Overall response rate (ORR), PFS, and OS were evaluated. Survival outcomes were estimated using the Kaplan-Meier method. Univariable Cox proportional hazards models were used to assess the association between BM burden and survival. Statistical analyses were performed in R (v4.3.3); p < 0.05 was set as significant. Results A total of 29 patients with mTNBC and confirmed BM at SG initiation were included. The median number of BM was 3 with median size of the biggest lesion 16.5 mm. Neurosurgical resection had been performed in 4 (14.3%) and CNS-directed radiotherapy in 28 (89.3%) patients prior to SG initiation. The median number of prior palliative systemic therapy lines was 2 (range: 1-3). The median follow-up was 6.05 months (IQR: 3.66-11.06; range: 0.79-27.47). At the time of analysis, 22 patients had died and 26 had the treatment with SG discontinued. The median OS was 8.9 months. Estimated OS rates at 3, 6, 9, and 12 months were 85.2%, 60.3%, 42.3%, and 28.2%, respectively. Median PFS was 3.09 months, with 3-, 6-, 9-, and 12-month PFS rates of 53.6%, 31.4%, 22.5%, and 12.0%, respectively. ORR was observed in 8 of 26 evaluable patients (30.8%). CNS progression was documented in 6 patients (23.1%). Neither the number nor the size of CNS lesions showed a statistically significant association with OS or PFS. SG administration required dose delays due to AEs in 15 patients (51.7%), and dose reductions in 11 (37.9%). Two cases (7.7%) of treatment discontinuation due to toxicity were reported. No unexpected new safety signals were observed. Conclusions SG demonstrated clinically meaningful activity and a manageable safety profile in this real-world cohort of patients with mTNBC and BM. Median PFS and OS outcomes appeared comparable or numerically favorable to those reported in the ASCENT BM subgroup analysis. Neither the number nor size of BM lesions significantly impacted outcomes, suggesting SG may be effective irrespective of intracranial disease burden. These data may support broader consideration of SG in routine management of CNS-involved TNBC.

A. Kordic, N. Ruel, N. Kethireddy; Medical Oncology, City of Hope, Duarte, CA.

Purpose: Antibody-drug conjugates (ADC) have made a profound impact on the treatment landscape of HR+/HER2-low and HR-/HER2-low metastatic breast cancer. Sacituzumab govitecan (Trodelvy) and trastuzumab deruxtecan (Enhertu) are ADC with topoisomerase I payloads bound to anti-Trop-2 and anti-HER2 monoclonal antibodies, respectively. Enhertu received FDA approval in 2022 based on the results of the DESTINY-Breast04 study as did Trodelvy in 2023 per the TROPiCS-02 study. The optimal sequencing of these agents (ET versus TE) remains a topic of debate and investigation in this patient population.Methods: Our retrospective, single center study evaluated 100 patients with HR+/HER2-low and HR-/HER2-low metastatic breast cancer who were treated sequentially with Enhertu and Trodelvy (ET vs TE) at the City of Hope Comprehensive Cancer Center from 01/2019-12/2023. Both groups had received at least one prior line of therapy in the metastatic setting. The primary objective was to estimate the median combined time to progression following ET vs TE (PFS1+ PFS2) to determine if the PFS for the 2^nd ADC declined significantly based on the sequence. PFS data was censored per the end-time point of the second treatment. Secondary endpoints included response rates (RR), treatment-related AE, and overall survival (OS). Patient demographics, treatment history, presence of visceral disease, and comorbidities were evaluated. Adverse event grading and investigator-assessed radiographic treatment response was determined using CTCAE v5.0 and RECIST 1.1 definitions, respectively. High-grade AE (hg-AE) was defined as Grade 3 or higher. HR and HER2 IHC status were assessed based on the most recent biopsy sample before each line of therapy. HR+ status included patients with 10% or greater ER/PR positivity and HER2-low included patients with IHC 1+/2+ with a negative FISH.Results: Most patients received ET (70/100) vs TE (30/100). The primary endpoint of PFS1 + PFS2 was comparable between the sequences (ET: 11.1 months vs TE: 8.2 months; log-rank p=0.7). The median PFS for Enhertu (ET: 6.8 months vs TE: 2.3 months; p < 0.0001) and Trodelvy (TE: 5.6 months vs ET: 2.5 months; p = 0.0006) was significantly increased when used first in the sequence. A similar trend was noted with RR for Enhertu (ET 65.7% vs TE 33.3%; p = 0.003) and Trodelvy (63.3% vs 25.7%; p = 0.0004) when given first in the sequence. Median OS was comparable between ET vs TE (22.9 months vs 17.5 months; p = 0.7). Neutropenia and GI toxicities were the most commonly reported AE with a similar rate of cumulative hg-AE in patients who received ET vs TE. In the ET group, there were significantly lower rates of hg-AE while on Enhertu compared to Trodelvy (28.5% vs 51.4%; p = 0.006), whereas rates were comparable (23.3% vs 40%; p = 0.2) in the TE group. The presence of baseline lung metastases was significantly higher in the ET group with 10 reported ILD events in the ET group vs 0 in the TE group. There were significantly more HR+ patients in the ET group, while HER2 IHC status was similar between groups (1+: 61% vs 2+: 28%).Conclusion: Patients with HR+/HER2-low and HR-/HER2-low metastatic breast cancer who received sequential ADC therapy with Enhertu and Trodelvy (ET or TE) had comparable PFS 1 + PFS2 and OS results. There were significant increases in PFS and RR with each ADC when used first compared to second in the treatment sequence. There were similar rates of cumulative hg-AE between the ET and TE groups with less hg-AE events in patients who received Enhertu with ET vs TE. Limitations of this study include the retrospective analysis and exclusion of patients who did not receive both drugs sequentially in the context of varied timelines of FDA approval. Prospective studies are needed to further evaluate the impact of ADC sequencing on treatment outcomes and toxicities.

C. Martin, o. castillo; Medical Oncology, Instituto Oncológico Nacional, panama, PANAMA.

Clinical and pathological characteristics of early hormone receptor-positive, HER2-negative breast cancer patients in Panama.Cristiane Martin-Palacios, Miguel Manzano, María Lim, Jonathan Quintero, José Amador, José Pinto, Taysser Sowley, Yaribeth Muñoz, Omar Castillo-Fernandez.Background: Breast cancer is the most common malignancy and a leading cause of mortality among women. In Latin America, clinical characteristics and treatment outcomes vary by region. Improving early detection and treatment has enhanced prognosis. In Panama, limited data exists, so gathering information on early hormone receptor-positive and HER2-negative breast cancer patients can help develop better treatment strategies.Methods: This retrospective study aims to describe the clinical and pathological characteristics of early hormone receptor-positive, HER2-negative breast cancer patients treated at the Instituto Oncologico Nacional between January 2017 and December 2019. Data was summarized using frequencies and percentages. We utilized Kaplan-Meier curves to analyze survival and recurrence rates. Recurrence factors were assessed through univariate analysis with the log-rank test and multivariate analysis using Cox regression.Results: We analyzed 368 patients, primarily women (98.9%, n = 365). The median age was 58 years. Most were postmenopausal (68.3%), and 55% had N0 disease. Staging showed 32.5% in stage I, 45.8% in stage II, and 21.1% in stage III. Regarding grade, 83% were grade 1 or 2, while 17% were grade 3. The median tumor size was 2.5 cm. Estrogen receptor positivity was 90%, and progesterone receptor positivity was 60%. In adjuvant treatment, 24.9% received tamoxifen, 56.8% aromatase inhibitors, and 17.6% sequential therapy.At the follow-up on May 31, 2025, 15.5% of patients had local or distant recurrence, and 10.3% had died; the median time to recurrence-free survival was not reached. Univariate analysis identified several risk factors for recurrence: premenopausal status (HR 1.76 CI 1.04-2.97; p=0.032), tumor size >2 cm (HR 2.40 CI 1.33-4.33; p=0.03), positive lymph nodes (HR 2.40 CI 1.33-4.33; p=0.03), grade 3 tumors (HR 2.08 CI 1.16-3.70; p=0.01), high nodal rate (HR 2.97 CI 1.59-5.54; p=0.001), stage III (HR 4.2), and use of aromatase inhibitors versus tamoxifen (HR 1.89). Multivariate analysis showed only stage III disease (HR 2.91 CI 2.49-7.04; p<0.001) and adjuvant tamoxifen use versus aromatase inhibitors (HR 2.27 CI 1.14-4.54; p = 0.02) were significantly associated with recurrence, while grade 3 tumors showed a trend toward significance (HR 1.84 CI 0.98-3.44; p = 0.055 ).Conclusion: Stage III, high-grade tumors, along with the use of adjuvant tamoxifen, are associated with a higher risk of recurrence. This underscores the need for strategies such as using GnRH analogs in premenopausal patients and implementing adjuvant CDK4/6 inhibitors for those at high risk within our institution.

E. Rohr¹, T. Alotaibi², F. Moria³, N. Bouganim⁴; ¹Department of Internal Medicine, Faculty of Medicine and Health Sciences, McGill University, Montréal, QC, CANADA, ²Department of Medical Oncology, The Medical Services of the Ministry of Interior, Riyadh, SAUDI ARABIA, ³Faculty of Medicine, King Abdulaziz University, Jeddah, SAUDI ARABIA, ⁴Department of Medical Oncology, McGill University Health Centre, Montréal, QC, CANADA.

Introduction:
Granulocyte colony-stimulating factors (G-CSF) are essential supportive agents for patients receiving myelosuppressive chemotherapy, reducing febrile neutropenia (FN) and preserving chemotherapy dose intensity, especially in high-risk or dose-dense regimens.¹⁻³ Guidelines recommend “primary prophylaxis” for patients at high risk for FN, while “secondary prophylaxis” is reserved for those with FN or borderline neutrophil counts during earlier cycles. While primary G-CSF benefits are well-documented, data on secondary prophylaxis, particularly in intermediate-risk regimens such as adjuvant doxorubicin-cyclophosphamide (AC) chemotherapy, are limited. Some studies suggest secondary G-CSF may reduce hospitalizations and improve treatment delivery, but robust, real-world, long-term safety data are lacking.⁵,⁶ A possible signal between G-CSF and secondary malignancies have been suggested.⁷ Accordingly, evaluation of the long-term safety of secondary prophylaxis is warranted. This study prospectively evaluated long-term safety and outcomes of secondary G-CSF prophylaxis in breast cancer patients treated with q3-weekly AC chemotherapy at the McGill University Health Centre. Methods:
We conducted an interim analysis of a prospectively maintained database at the McGill University Health Centre (2016-2025). Ninety-eight patients who received q3-weekly AC chemotherapy (doxorubicin 60 mg/m² and cyclophosphamide 600 mg/m²) in the adjuvant or neoadjuvant setting, were included. Patients treated with dose-dense regimens or meeting criteria for primary G-CSF prophylaxis were excluded. Secondary G-CSF (filgrastim or pegfilgrastim) was administered at physician discretion to prevent dose reductions or delays. Key outcomes, including metastatic recurrence, mortality, overall survival, and follow-up time, were assessed using multivariable logistic regression and Cox proportional hazards models, adjusting for age, stage at diagnosis, and tumour subtype. All statistical analyses were conducted using R (v4.5.1). Results:Of 98 patients, 44 (45%) received secondary G-CSF. Fifty-eight percent of patients received G-CSF at cycle 2. Baseline characteristics were balanced between groups. No statistically significant difference in the incidence of new metastases was observed between the G-CSF and non-G-CSF groups (7.5% vs. 19.6%; adjusted OR 0.25, 95% CI 0.04-1.09; p = 0.09). No significant difference in all-cause mortality was observed (25% vs. 13%; adjusted OR 2.09, 95% CI 0.61-7.70; p = 0.25). Survival outcomes were comparable (5-year OS: 86.4% vs. 90.7%; adjusted HR 1.92, 95% CI 0.71-5.18; p = 0.20). Median follow-up among survivors was similar (96.8 vs. 94.6 months), with five-year follow-up exceeding 84% in both cohorts. No secondary hematologic malignancies occurred in either group. Conclusion:
In this real-world cohort, secondary G-CSF prophylaxis during q3-weekly AC chemotherapy was not associated with significant differences in all-cause mortality between groups. No secondary hematological malignancies were observed. These results support the liberal use of secondary G-CSF in curative-intent regimens to prevent delays or reductions in dose intensity. Continued follow-up of this cohort is warranted to confirm long-term safety of liberal G-CSF use.

W. Yeo¹, L. Yuen², C. Kwok³, I. Soong⁴, J. Chiu⁵, T. Ng⁶, S. Chan⁷, T. Wong², C. Yolanda⁸, L. Lawrence⁹, C. Yau⁹, W. Hung⁹, C. Polly⁹; ¹Clinical Oncology, Chinese University of Hong Kong, Hong Kong, HONG KONG, ²Surgery, Hong Kong Breast Cancer Foundation, Hong Kong, HONG KONG, ³Clinical Oncology, Princess Margaret Hospotal, Hong Kong, HONG KONG, ⁴Clinical Oncology, Pamela Youde Nethersole Eastern Hospital, Hong Kong, HONG KONG, ⁵Clinical Oncology, University of Hong Kong, Hong Kong, HONG KONG, ⁶Clinical Oncology, Tuen Mun Hospital, Hong Kong, HONG KONG, ⁷Surgery, United Christian Hospital, Hong Kong, HONG KONG, ⁸Clinical Oncology, CUHK Medical Centre, Hong Kong, HONG KONG, ⁹Clinical Oncology, Hong Kong Breast Cancer Foundation,, Hong Kong, HONG KONG.

Background:Adjuvant endocrine therapy (ET) therapy combining with CDK4/6 inhibitors have improved outcomes of early-staged breast cancer (EBC) patients (pts) with intermediate- or high- risk HR-positive HER2-negative disease based on MonarchE and NATALEE studies. The objective of this study was to assess the invasive disease-free survival (iDFS) of HR-positive HER2-negative EBC patients prior to the use of adjuvant CDK4/6 inhibitors. Methods: This is a retrospective study based on data extraction from the Hong Kong Breast Cancer Registry. Pts from 11 public and 4 private hospitals/clinics were consented for data collection. The study protocol was approved by the regional ethics committee of individual units. Pts with HR-positive HER2-negative EBC who underwent definitive surgery between January 2006 and December 2011 were studied. The inclusion criteria of NATALEE were applied. Pts were divided into two groups: group 1, those who satisfied NATALEE criteria (considered to have intermediate- or high- risk); group 2, those not eligible for NATALEE and had stage 1 cancers. Pts background characteristics were collected. iDFS was evaluated using the Kaplan-Meier method. Descriptive statistics were used to report the clinical outcomes between the two groups. Results: A total of 3512 pts were included; 1885 (53.7%) in group 1 and 1627 (46.3%) in group 2. The median age was 50.2 years (range: 24.2-101.4). 1624 (46.2%) were premenopausal, 1670 (47.6%) were postmenopausal while 218 (6.2%) had unknown menopausal status at diagnosis. 883 (25.2%) had grade 3 cancers. High tumour Ki67 (defined as >/=20%) was reported in 790 (25.2%) patients. 2459 (70.0%) received adjuvant radiotherapy, 2230 (63.5%) underwent adjuvant chemotherapy. 3341 patients received adjuvant ET (95.1%). For group 1 vs group 2, the 10-year iDFS were 77.1% vs 89.6% respectively. iDFS data according to age, menopausal status, grading, Ki-67, use of adjuvant chemotherapy and radiotherapy, are listed in Tabel 1. Conclusions: The present study confirmed that in the era prior to adjuvant ET plus CDK4/6 inhibitor, patients who had intermediate- or high- risk HR-positive HER2-negative EBC had worse prognosis. Among those who would have satisfied NATALEE criteria (group 1), older age and postmenopausal at diagnosis had significantly worse iDFS, while use of adjuvant chemotherapy was associated with better iDFS. For those with stage 1 EBC (group 2), older age and high tumour grade had significantly worse iDFS, while having receiving adjuvant radiotherapy was associated with better iDFS. Real-world studies such as the present one provide informative data and further studies may enable better determination of appropriate patient population for the use of adjuvant CDK4/6 inhibitor treatment