Poster Spotlight 12: Contemporary Locoregional Challenges: Time to De-escalate?

S. M. Wong¹, E. Blondeaux², V. Delucchi², F. Coussy³, R. Bernstein Molho⁴, S. Linn⁵, A. Di Meglio⁶, A. Kwong⁷, K. Pogoda⁸, E. Agostinetto⁹, I. Nevelsteen¹⁰, J. Balmana¹¹, H. C. Moore¹², A. Toss¹³, A. Ferrari¹⁴, C. Rousset-Jablonski¹⁵, T. Renaud¹⁶, K. Phillips¹⁷, F. A. PeccatorI¹⁸, M. Agustina Ipina¹⁹, S. Paluch-Shimon²⁰, J. Ryu²¹, W. Kui¹⁷, M. Lee²², R. Fruscio²³, M. Rozenblit²⁴, C. Vernieri²⁵, A. Matikas²⁶, M. Dieci²⁷, F. J. Couch²⁸, L. De Marchis²⁹, S. E. Hwang³⁰, D. Aguilar-y Mendez³¹, D. Can Guven³², M. Swain³³, C. Gianni³⁴, S. Spinaci³⁵, G. Montagna²², M. Lambertini³⁶, H. Kim³⁷; ¹Department of Surgery and Oncology, McGill University and JGH Stroll Cancer Prevention Centre, Montreal, QC, CANADA, ²Clinical Trial Unit, Epidemiologia Clinica, Ospedale Policlinico San Martino, Genova, ITALY, ³Department of Medical Oncology, Institut Curie-Institut of Women’s Cancers, Paris, FRANCE, ⁴Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, Chaim Sheba Medical Center, Ramat Gan, ISRAEL, ⁵Department of Molecular Pathology, Netherlands Cancer Institute (NKI),, Amsterdam, NETHERLANDS, ⁶Département Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, Villefuif, FRANCE, ⁷Cancer Genetics Centre and Breast Surgery Centre, Hong Kong Sanatorium and Hospital, Hong Kong, HONG KONG, ⁸Department of Breast Cancer and Reconstructive Surgery, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, POLAND, ⁹Service de Oncologie, Université libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (H.U.B), Institut Jules Bordet, Bruxelles, BELGIUM, ¹⁰Surgery and Oncology, University Hospitals Leuven, KU Leuven, Leuven, BELGIUM, ¹¹Hereditary Cancer Genetics Unit, Medical oncology Department, Vall d´Hebron University Hospital, Vall d´Hebron Institute of Oncology (VHIO), Barcelona, SPAIN, ¹²Department of Medical Oncology, Cleveland Clinic Taussig Cancer Institute, Cleveland, OH, ¹³Department of Oncology and Haematology, Azienda Ospedaliero-Universitaria Policlinico di Modena, Modena, ITALY, ¹⁴Hereditary Breast and Ovarian Cancer (HBOC) Unit and General Surgery, Fondazione IRCCS Policlinico San Matteo & University of Pavia, Pavia, ITALY, ¹⁵Department of Surgery, Leon Berard Cancer Center, Lyon, FRANCE, ¹⁶Cancer Genetics Unit, Bergonie Institute, Bordeaux, FRANCE, ¹⁷Department of Medical Oncology, Peter MacCallum Cancer Centre, The University of Melbourne, Melbourne, AUSTRALIA, ¹⁸Gynecologic Oncology Department, European Institute of Oncology (IRCCS), Milan, ITALY, ¹⁹-, SUMA (Grupo Cooperativo Argentino para el Estudio y la Investigación del Cáncer de Mama), Buenos Aires, ARGENTINA, ²⁰Medial Oncology & Faculty of Medicine, Sharett Institute of Oncology, Hadassah University Hospital & Hebrew University, Jerusalem, ISRAEL, ²¹Department of Surgery, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, KOREA, REPUBLIC OF, ²²Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Centre, New York, NY, ²³UO Gynecology, Department of Medicine and Surgery, IRCCS San Gerardo dei Tintori & University of Milan-Bicocca, Monza, ITALY, ²⁴Department of Medical Oncology, Yale University, New Haven, CT, ²⁵Medical Oncology Department, Breast Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ITALY, ²⁶Department of Oncology/Pathology, Karolinska Institute and Breast Center, Karolinska University Hospital, Stockholm, SWEDEN, ²⁷Dipartimento di Scienze Chirurgiche, Oncologiche e Gastroenterologiche, Università di Padova, Padova, ITALY, ²⁸Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, ²⁹Department of Radiological, Oncological and Pathological Sciences, Sapienza University of Rome, Rome, ITALY, ³⁰Department of Surgery, Duke University, Durham, NC, ³¹Medical Genetics, Breast Cancer Center, Hospital Zambrano Hellion – TecSalud, Tecnologico de Monterrey, Nuevo León, MEXICO, ³²Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, TURKEY, ³³Department of Obstetrics and Gynecology, Wayne State University School of Medicine and Michigan State University (MSU), Detroit, MI, ³⁴Medical Oncology, Breast & Gynecology Unit, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) “Dino Amadori”, Meldola, Italy, ITALY, ³⁵Chirurgia Senologica, Ospedale Villa Scassi, Genova, ITALY, ³⁶Department of Medical Oncology, Clinica di Oncologia Medica, IRCCS Ospedale Policlinico San Martino, Genova, ITALY, ³⁷Division of Breast Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, KOREA, REPUBLIC OF.

Background: Young BRCA carriers may undergo breast conserving surgery (BCS) or mastectomy with or without contralateral risk reducing mastectomy at the time of an index breast cancer diagnosis. A variety of factors may influence surgical decision making. Methods: The BRCA BCY Collaboration (NCT03673306) is an international, hospital-based, retrospective cohort study conducted at 109 centres across 5 continents including women with germline pathogenic or likely pathogenic variants (PV) in BRCA1/2 diagnosed between 2000 and 2020 with invasive stage I-III breast cancer prior to or at age 40 years. The primary objective of the present analysis was to evaluate surgical management in these patients. Breast surgery was defined as BCS, unilateral mastectomy, or bilateral mastectomy administered as part of primary treatment for a first diagnosis of invasive breast cancer. Multivariable logistic regression was used to determine factors associated with receipt of bilateral mastectomy. Results: Of 5660 eligible BRCA1/2 carriers, 4715 had unilateral stage I-III breast cancer with surgical treatment details available. The median age of the cohort was 35 years (IQR, 31-38 years). Overall, 1805 (38.3%) patients underwent BCS, 1752 (37.2%) underwent unilateral mastectomy, and 1158 (24.6%) underwent bilateral mastectomy. The proportion of young BRCA1/2 carriers undergoing BCS decreased over the study period (55.7% in 2000 vs. 27.0% in 2020), whereas the use of bilateral mastectomy significantly increased (8.0% in 2000 vs. 44.4% in 2020). Bilateral mastectomy was more common in women who had genetic testing performed before (57.0%) or within 6 months of a breast cancer diagnosis (38.5%), compared to those tested after diagnosis (5.1%, p<0.001). On multivariable analysis, compared to those tested after diagnosis, earlier genetic testing remained the strongest predictor of bilateral mastectomy receipt (testing prior to diagnosis: OR 20.7 [95% CI 15.3-28.1]; testing at diagnosis: OR 6.8 [95% CI 5.4-8.7]). Other predictors of bilateral mastectomy receipt included geographic region, later year of diagnosis, smaller tumor size, node negative disease, and neoadjuvant treatment. In subgroup analysis including 2327 patients who had genetic testing performed before or within 6 months of diagnosis, 42.0% underwent bilateral mastectomy, with the lowest rates reported in Asia/Africa (26.1%) and the highest rates reported in North America (66.4%, p<0.001). In adjusted subgroup analyses, BRCA1 PV, later year of diagnosis, smaller tumor size, node negative disease, neoadjuvant treatment, and geographic region remained independently associated with bilateral mastectomy. Conclusions: In this large, international study of young affected BRCA carriers, geographic region and timing of genetic testing strongly impacted surgical management. These data support early genetic testing for young women with breast cancer to help optimize local therapy decisions.

N. S. Kim¹, A. Vertido², A. Quirarte³, H. Batra-Sharma⁴, E. Abeles³, J. Moya³, J. Chien⁵, J. Mouabbi⁶, R. Mukhtar²; ¹Surgery, Georgetown University School of Medicine, Washington D.C., DC, ²Breast Surgical Oncology, General Surgery, University of California San Francisco, San Francisco, CA, ³Surgery, University of California San Francisco, San Francisco, CA, ⁴Medical Oncology, Hematology, University of California San Francisco, San Francisco, CA, ⁵Breast Medical Oncology, University of California San Francisco, San Francisco, CA, ⁶Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX.

Background: The monarchE and NATALEE trials demonstrated significant improvement in invasive disease-free survival with the combination of adjuvant endocrine therapy and a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i). Namely, abemaciclib and ribociclib have been used in hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer. By inhibiting cell cycle progression, both abemaciclib and ribociclib can significantly improve invasive disease-free survival in selected patients. Standard indications for adjuvant CDK4/6i therapy include larger tumor size, nodal involvement, or high-risk features such as high grade, high proliferation, or high-risk genomic assay score. However, limited data exist on the indications for and use of CDK4/6i in invasive lobular carcinoma (ILC). ILC is the second most common subtype of breast cancer, comprising up to 15% of all breast malignancies. Nearly 90% of these tumors exhibit HR-positive and HER2-negative status, and they frequently present at a later stage with more indolent features such as lower grade, lower Ki-67, and less lymphovascular invasion than invasive ductal carcinoma. We hypothesized that given these features, a majority of patients with ILC only become eligible for CDK4/6i treatment because of their nodal status. If true, this has implications for the role of surgical staging of the axilla in patients with ILC. Methods: We retrospectively analyzed a prospectively maintained institutional ILC database to identify patients with stage I-III, HR-positive, HER2-negative ILC. Patients were considered eligible for adjuvant CDK4/6i treatment if they met any of the following criteria: nodal positivity, tumor size ≥ 5 cm, or tumor size 2-5 cm with either tumor grade 3, Ki-67 ≥ 20%, or high-risk genomic assay score (MammaPrint high risk or Oncotype Dx score ≥ 26). We determined the proportion of patients with ILC who were eligible for CDK4/6i therapy overall; among those, we evaluated which eligibility criteria were met and what proportion of patients would be considered ineligible in the absence of nodal staging data. Results: From 1,027 ILC cases, we included 861 patients with stage I-III, HR-positive, HER2-negative tumors. Overall, 390 (45.3%) met at least one eligibility criteria for treatment with a CDK4/6 inhibitor. Of those, the most common indication for CDK4/6 inhibitor treatment was nodal positivity, present in 255 (65.4%) patients; the mean number of positive nodes was 4.0 (range= 1-46). The next most common criteria was tumor size ≥ 5 cm (n= 201, 51.5%), followed by Ki67 >20% (n= 23, 5.9%), high-risk genomic assay (n= 11, 2.8%), or tumor grade 3 (n= 8, 2.1%). Of the 255 patients with nodal positivity, 121 (47.5%) met no other eligibility criteria for CDK4/6i treatment, whereas 107 (42.0%) also had a tumor size ≥ 5 cm and 27 (10.6%) also had other high-risk features. In total, 31.0% (121/390) of patients eligible for CDK4/6i therapy met criteria for treatment based on nodal status alone. Conclusion: In patients with early stage ILC, nodal positivity is the most common indication for treatment with CDK4/6 inhibitor, consistent with our hypothesis. These data suggest that implementation of surgical de-escalation strategies, namely the omission of sentinel lymph node surgery, should be applied with caution in patients with ILC. Nearly one third of ILC patients eligible for CDK4/6i therapy may no longer meet treatment criteria in the absence of confirmed nodal positivity, which is often difficult to detect based on imaging alone.

M. Heidinger¹, T. A. Zwimpfer², F. Halbeisen³, N. Maggi¹, M. Frevert¹, R. Kiblawi¹, J. M. Loesch¹, F. D. Schwab¹, C. Kurzeder¹, G. Montagna⁴, W. P. Weber¹; ¹Breast clinic, University Hospital Basel, Basel, SWITZERLAND, ²Gynaecology & Obstetrics, University Hospital Basel, Basel, SWITZERLAND, ³Surgical Outcome Research Center, University Hospital Basel, Basel, SWITZERLAND, ⁴Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY.

Introduction The SOUND and INSEMA trials demonstrated that sentinel lymph node biopsy (SLNB) can be safely omitted in patients with small, hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC) who are clinically and imaging node-negative (cN0/iN0). However, recruitment for these trials ended prior to the approval of adjuvant cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, which rely in part on nodal status for eligibility. Therefore, the extent to which SLNB omission impacts eligibility for CDK4/6 inhibitors and consequently oncological outcomes is unknown. Methods This was a single-center, retrospective cohort study of patients with clinically T1 and T2, cN0/iN0, HR-positive/HER2-negative BC who underwent breast-conserving surgery with a SLNB between 01/2014-12/2024. Preoperative axillary ultrasound was used throughout the study period. CDK4/6 inhibitor eligibility was estimated based on the monarchE and NATALEE inclusion criteria. Abemaciclib eligibility included patients with ≥4 positive lymph nodes, or 1-3 positive lymph nodes and either grade 3 disease, tumor size ≥5cm, or Ki67 ≥20%. 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 ribociclib treatment. Predictors of CDK4/6 inhibitor eligibility and node-positivity were identified utilizing multivariable logistic regression models. Estimates of the impact on invasive disease-free survival are based on the five- and three-year results of the monarchE and NATALEE trials, respectively. Results Of 309 patients, 78.3% (242/309) were postmenopausal, 28.8% (89/309) had a ≥pT2 tumor, and 14.6% (45/309) had pN1 disease. 21.4% (66/309) qualified for adjuvant CDK4/6 inhibitor treatment. 6.1% (19/309) were eligible for abemaciclib and 7.8% (24/309) were eligible for ribociclib based on node criteria. Consequently, 17 (95%CI 11-27) and 13 (95%CI 9-20) patients would be required to undergo SLNB in order to identify one patient qualifying for abemaciclib and ribociclib (based on node-criteria), respectively. Predictors of CDK4/6 inhibitor eligibility were found to be pathological tumor stage ≥pT2 (odds ratio [OR] 10.3, 95%CI 4.5-25.1, p<0.001), Ki67 ≥20% (OR 4.9, 95%CI 2.3-10.5, p<0.001), and lymphovascular invasion (OR 4.6, 95%CI 2.0-10.7, p<0.001). Lymphovascular invasion (OR 5.3, 95%CI 2.4-11.5, p<0.001) was found as the sole predictor for node-positivity. Based on the 5-year monarchE (NNT=28) and 3-year NATALEE (NNT=63) data, it was estimated that 3 (95%CI 2-4) and 2 (95%CI 1-2) patients, out of 1000, would experience a recurrence upon omission of the SLNB due to lack of candidacy for abemaciclib and ribociclib, respectively.A subgroup analysis of patients with cT1 tumors (n=223) demonstrated that 4.5% (10/223) of patients were eligible for abemaciclib and 8.1% (18/223) for ribociclib based on node-criteria. The number of patients required to undergo a SLNB was 23 (95%CI 13-47) and 13 (95%CI 9-21) for eligibility for abemaciclib and ribociclib (based on node criteria), respectively. Omission of SLNB in a collective of 1000 patients would result in 3 (95%CI 1-3) and 2 (95%CI 1-2) patients experiencing recurrences due to missed treatment with abemaciclib and ribociclib, respectively. Conclusion Omission of SLNB in patients with small HR+/HER2- tumors results in a missed indication for CDK4/6 inhibitors in <10% of patients with minimal impact on recurrence. SLNB should not routinely be performed in patients who meet SOUND/INSEMA criteria.

R. F. Hwang¹, W. E. Barlow², K. Kalinsky³, R. Jagsi⁴, L. Pusztai⁵, A. Thompson⁶, G. N. Hortobagyi⁷, P. Sharma⁸, F. Meric-Bernstam⁹; ¹Breast Surgical Oncology, UT-MD Anderson Cancer Center, Houston, TX, ²Cancer Research and Biostatistics, SWOG; University of Washington, Seattle, WA, ³Medical Oncology, Emory University, Winship Cancer Institute, Atlanta, GA, ⁴Radiation Oncology, Emory University, Winship Cancer Institute, Atlanta, GA, ⁵Medical Oncology, Yale University Cancer Center, New Haven, CT, ⁶Surgical Oncology, Section of Breast Surgery, Baylor College of Medicine, Houston, TX, ⁷Breast Medical Oncology, UT-MD Anderson Cancer Center, Houston, TX, ⁸Medical Oncology, University of Kansas Medical Center, Westwood, KS, ⁹Investigational Cancer Therapeutics; Breast Surgical Oncology, UT-MD Anderson Cancer Center, Houston, TX.

Background: The SWOG S1007 (RxPONDER) trial demonstrated that premenopausal women with hormone receptor-positive, Her2-negative breast cancer, 1–3 positive nodes, and Recurrence Score (RS) < 26 benefit from adjuvant chemotherapy, but postmenopausal women do not. Most patients in RxPONDER underwent axillary lymph node dissection (ALND) to stage the axilla; however, axillary management has evolved. It is unclear whether the RxPONDER trial results were similar in patients who had sentinel lymph node biopsy (SLNB) only versus ALND.Methods: We performed a secondary analysis from RxPONDER to evaluate whether clinical outcomes differed between patients undergoing SLNB alone versus ALND. Endpoints included invasive disease-free survival (IDFS), distant relapse-free survival (DRFS), and locoregional recurrence (LRR).Results: Of 4980 women with available surgical data, 1847 (37%) had SLNB only, 707 (14%) ALND only, and 2426 (48.7%) both SLNB and ALND. Compared to the SLNB + ALND group, the SLNB-only group was older, postmenopausal, obese, and more likely to undergo partial mastectomy. Tumors were lower-grade, smaller, more often ductal, and less likely to be multicentric or have lymphovascular invasion (LVI). RS was similar across groups. SLNB-only patients had fewer nodes removed, less internal mammary node involvement, fewer positive nodes, and smaller SLN metastases. Those with a single positive node had a similar profile. On multivariate analysis, postmenopausal status and obesity increased the likelihood of SLNB alone; larger tumors and LVI decreased it. Among 1774 mastectomy patients, 352 had SLNB only; they were more often postmenopausal and obese, with otherwise similar features. IDFS, DRFS, and LRR were comparable across axillary surgery types after adjustment for clinical variables. In premenopausal SLNB-only patients (N=550), the chemotherapy arm had numerically improved IDFS (HR 0.68; 95% CI 0.43–1.07; p=0.09) and LRR (HR 0.45; 95% CI 0.14–1.42; p=0.17), though not statistically significant. This result is consistent with the main trial effect. Among SLNB-only patients who underwent partial mastectomy, 96% received adjuvant radiation.Conclusions: In this secondary analysis of RxPONDER, over one-third of patients underwent SLNB alone. These patients were older, more likely postmenopausal, and had more favorable tumors. Despite having less nodal surgery with fewer nodes removed, outcomes including IDFS, DRFS, and LRR were similar to those who underwent more extensive surgery. Among premenopausal patients, chemotherapy was associated with numerically better outcomes in the SLNB-only group, though not statistically significant. These findings support the safety of SLNB alone in selected patients and suggest further study in key subgroups.Funding: NIH/NCI/NCTN grants U10CA180888, U10CA180819

T. Amburn¹, A. Mamtani¹, J. J. Chen², V. Sevilimedu³, S. Shen⁴, K. Jhaveri⁴, M. Morrow¹; ¹Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, ²Department of Medicine, New York Presbyterian Weill Cornell, New York, NY, ³Biostatistics Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, ⁴Breast Medicine Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY.

Background: Among stage 1, clinically node-negative (cN0), hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer patients with a negative preoperative axillary ultrasound (AxUS), the omission of sentinel lymph node biopsy (SLNB) has been demonstrated to be noninferior to upfront axillary surgery. However, the applicability of this approach to invasive lobular carcinoma (ILC) remains uncertain due to the unreliability of AxUS in ILC and perceived higher risk of nodal upstaging. We sought to evaluate the rate and predictors of axillary nodal upstaging in a cohort of patients with ILC who met SOUND trial criteria. Methods: We retrospectively identified all patients diagnosed with ILC who underwent preoperative axillary ultrasound and upfront surgery including SLNB between 2009 and 2024. cT1, cN0 patients with normal preoperative AxUS were defined as SOUND-eligible (JAMA Oncol 2023). Patients who underwent neoadjuvant systemic therapy (NAST) were excluded. Clinicopathologic characteristics and nodal burden were examined. Both macro- and micrometastasis were included as pathologic nodal metastasis. Descriptive statistics and logistic regression analysis was performed using software R 4.4.2. Results: From an overall cohort of 1059 patients with cT1-3, cN0-2 ILC without NAST who underwent preoperative AxUS and upfront surgery including SLNB, 662 (62.5%) met SOUND trial selection criteria (cT1, cN0 ILC with normal preoperative AxUS). The median age was 60 years (IQR 51-68), median pathologic tumor size was 1.3 cm (IQR 0.9-2.0), and the majority of tumors were classic-type (549, 82.9%), HR+/HER2- (639, 96.5%), and grade 2 (587, 89%). Nodal metastases (pN+) were identified in 116 (17.5%) cases: 24 (3.6%) were pN1mic, 77 (11.6%) pN1, 8 (1.2%) pN2, and 7 (1.0%) pN3. On univariate analysis, histologic grade 3 (OR 3.21, 95% CI 1.01-10.4, p=0.046), lymphovascular invasion (LVI)(OR 6.88, 95% CI 3.51-13.7, p<0.001), and premenopausal status (OR 1.58, 95% CI 1.93-2.41, p=0.033) were significantly associated with pN+ disease. On multivariate analysis, LVI (OR 6.24, 95% CI 3.14-12.6, p<0.001) was the only independently associated factor with the finding of pN+ disease. Due to only a few upstaging events to pN2-3 (n=15), UVA and MVA could not be performed in this subgroup. LVI was present in 5 (33.3%) of the 15 cases with pN2-3 upstaging. Conclusions: In this cohort of ILC who met SOUND eligibility criteria, 17.5% of patients were node positive, and only 2.2% of patients had extensive nodal upstaging (pN2-3). High-risk features, such as presence of LVI, premenopausal status, and high grade, may be useful for decision making for omission of SLNB in stage 1 ILC patients.

T. Jarm¹, N. Besic², R. Cencelj Arnez², J. But Hadzic³, I. Ratosa³; ¹Medical faculty, University of Ljubljana, Ljubljana, SLOVENIA, ²Division of Surgery, Institute of Oncology Ljubljana, Ljubljana, SLOVENIA, ³Division of Radiotherapy, Institute of Oncology Ljubljana, Ljubljana, SLOVENIA.

Background: Research indicates that up to two-thirds of patients with early breast cancer experience arm or shoulder pain or other symptoms following surgery and radiotherapy. The relationship between morbidity and dose administered to the humeral head is still not fully understood. We seek to determine if the radiation dose to humeral head, radiation technique (3D-CRT versus IMRT/VMAT), and fractionation schedule—correlates with the patient-reported outcomes measures (PROMs). Methods: We identified patients who underwent surgery and postoperative radiation therapy for early breast cancer and were included in the institutional prospective database of the Early Individualized Integrated Rehabilitation Program – OREH between November 2019 and April 2023. These patients had completed the EORTC QLQ-C30 and BR23 questionnaires prior to surgery/at baseline and 12 months after the start of treatment. Retrospective delineations of the humeral head and humeral head PRV with a 1 cm safety margin were implemented for each case. The treatment planning parameters for all treatment plans were subsequently obtained. 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. The mean values were compared using the non-parametric Kruskal-Wallis test. Results: We enrolled 298 patients in this study. The majority of patients were treated with breast conserving surgery (N=210; 70.5%) and sentinel lymph node biopsy (N=200; 67.1%). The majority of patients (N=194, 65.1%) underwent moderate hypofractionation consisting of 15-16 fractions of 2,67 Gy with or without tumor bed boost. Regional nodal irradiation (RNI) to levels I-IV with or without internal mammary lymph nodes irradiation was delivered to 121 (40.6%) patients. Any pain in arm or shoulder was reported by 110 (36.9%) and 189 (63.4%) patients at baseline and 12 months after treatment start, respectively. Median Dmean doses to humeral head and humeral head PRV were 2.3 Gy (range 0-33.9 Gy) and 3.6 Gy (range 0-30 Gy), respectively. Multivariate ordinal regression model analysis confirmed a statistically significant association between the dose received by 2% of the humeral (D2%) (p=0.044), volume of humeral head receiving ≥10 Gy (V10Gy) (p=0.028) and V20 Gy (p=0.045) and any pain in arm or shoulder 12 months after diagnosis. At baseline and 12 months after treatment initiation, 39 (13.1%) and 142 (47.7%) patients, respectively, reported any difficulties in raising or moving their arm sideways. This was correlated with humeral head V20 Gy (p=0.029) and V30 Gy (0.035) in a multivariate analysis. Irradiation to lymph node regions, radiation technique (3D-CRT versus IMRT/VMAT), fractionation schedule (hypofractionation versus conventional fractionation), type of breast and axillary surgery were not correlated with arm or shoulder pain (or other symptoms) and PROMs. Conclusions: The irradiation of the humeral head correlates with the development of arm or shoulder symptoms following surgery and radiotherapy for early breast cancer. More research is needed toward identifying dose to organs at risk that will be considered when planning future radiation therapy.

J. G. Bazan¹, A. Meisner², K. Kalinsky³, E. Connolly⁴, W. E. Barlow², W. Woodward⁵, A. Thompson⁶, D. A. Lew², P. Sharma⁷, L. Pusztai⁸, R. Jagsi⁹; ¹Radiation Oncology, City of Hope Comprehensive Cancer Center, Duarte, CA, ²SWOG Statistics and Data Management Center, Fred Hutchinson Cancer Center, Seattle, WA, ³Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, ⁴Radiation Oncology, Columbia University Herbert Irving Comprehensive Cancer Center, New York, NY, ⁵Breast Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, ⁶Division of Surgical Oncology, Baylor College of Medicine, Houston, TX, ⁷Medical Oncology, University of Kansas Comprehensive Cancer Center, Kansas City, KS, ⁸Medical Oncology, Yale University School of Medicine, New Haven, CT, ⁹Radiation Oncology, Emory University School of Medicine, Atlanta, GA.

Background: Comprehensive regional nodal irradiation (RNI) after either breast conserving surgery (BCS) or mastectomy (Mx) remains a standard of care for the majority of patients with breast cancer and axillary nodal macrometastases. However, for patients with nodal micrometastases (pN1mi), the benefit of RNI is less clear since these patients were not included in the historical trials. To date, little is known about RNI patterns of care or cancer control outcomes in patients with pN1mi disease. The SWOG 1007 (S1007) trial included hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) patients with pN1mi disease. All patients randomized to the intervention (chemotherapy+endocrine therapy versus endocrine therapy alone) had Oncotype DX Score of 0-25. While RT was not directed by the protocol, data on RT use and targets was prospectively collected. Here, we report the patterns of care of RT use in patients with pN1mi disease. Materials/Methods: We reviewed the pathology reports of all patients enrolled on S1007 from 2011-2014, prior to an amendment that excluded patients with pN1mi disease. We identified patients with only pN1mi disease. We used the Radiation Therapy (RT) forms captured during the study to classify patients into 1 of 4 groups: 1) no RT, 2) Breast/Chestwall (CW) + Axillary RT, 3) Breast/CW RT, 4) RNI. Axillary RT was defined as irradiation of the level I and/or level II axilla without treatment of the supraclavicular (SCL) region. RNI was defined as inclusion of a SCL field. The analysis is primarily descriptive with use of chi-square test or t-test to compare groups. We also fit a multivariate logistic regression model to estimate the odds ratio (OR) for the associations of individual factors with RNI vs. other or no RT. Results: From 2486 patients enrolled prior to the amendment, we identified 599 patients (24%) with only pN1mi disease. Of these, 573 patients had RT forms available. The majority were postmenopausal (66%), most had undergone BCS (65%), the median number of axillary nodes removed was 3 (interquartile range (IQR), 2-6), and 87% (N=500) had pN1mi disease limited to 1 node. In addition, 61% of patients were treated with endocrine therapy (ET) alone and the median Oncotype DX score was 15 (IQR, 11-19). The overall distribution of RT use was 29% no RT, 10% Breast/CW+axillary RT, 47% breast/CW only, and 15% RNI. No patients received axillary RT without treatment of the breast/CW. Omission of RT was significantly more frequent in patients treated with Mx compared to BCS: 73% (148/202) vs. 4% (15/371), p1 node involved (OR=2.34, 95% CI 1.29-4.24, p=0.005) and T2-T3 tumors vs. T1 tumors (OR=1.93, 95% CI 1.20-3.11, p=0.007). Conclusion: We characterized RT patterns of care in a large cohort of patients with pN1mi disease who were enrolled on S1007. Nearly 75% of patients that underwent Mx did not receive RT and only 15% of all patients received RNI suggesting significant de-escalation of RT occurred in these patients. These variations in RT practice patterns should encourage enrollment of patients with pN1mi disease onto the ongoing TAILOR RT trial, which is investigating the role of RNI in patients with HR+/HER2-, pT1-2 disease with low volume axillary burden (including only pN1mi disease) and Oncotype RS≤25.

E. Hahn¹, R. Sutradhar², F. Johri³, D. Rodin¹, K. J. Jerzak⁴, L. Nguyen⁵, S. Trebinjac⁶, C. Fong⁵, L. Paszat⁷, E. Rakovitch⁷; ¹Department of Radiation Oncology, Princess Margaret Cancer Centre and University of Toronto, Toronto, ON, CANADA, ²Cancer Research Program, ICES and University of Toronto, Toronto, ON, CANADA, ³Department of Radiation Oncology, University of Toronto, Toronto, ON, CANADA, ⁴Medical Oncology, Sunnybrook Health Sciences Centre and University of Toronto, Toronto, ON, CANADA, ⁵Cancer Research Program, ICES, Toronto, ON, CANADA, ⁶Evaluative Clinical Sciences, Sunnybrook Research Institute, Toronto, ON, CANADA, ⁷Department of Radiation Oncology, Sunnybrook Health Sciences Centre and University of Toronto, Toronto, ON, CANADA.

Background: Most individuals diagnosed with ductal carcinoma in situ (DCIS) undergo breast-conserving surgery (BCS) followed by whole-breast radiotherapy (RT). Historically, there have been concerns about increased cardiac risk from breast RT, particularly for left-sided lesions. With the implementation of modern RT techniques and cardiac avoidance protocols, the long-term impact of RT on cardiac outcomes in DCIS remains uncertain. Methods: We conducted a retrospective, population-based cohort study of women diagnosed with pure DCIS in Ontario from 1994 to 2014 who underwent BCS with or without RT. Clinical and pathological characteristics, comorbidity burden (Elixhauser index), socioeconomic status, and treatment variables including laterality and RT receipt were obtained from the Ontario DCIS database and linked administrative datasets. Pre-existing cardiovascular disease and subsequent cardiac events were identified using hospital discharge data. Primary outcomes included acute myocardial infarction (AMI), coronary revascularization (Percutaneous Coronary Intervention (PCI) or Coronary Artery Bypass Grafting (CABG)), death due to ischemic heart disease (IHD), and a composite of these events. Fine-Gray competing risk regression was used to estimate the impact of RT, adjusting for age and baseline cardiac disease. Cumulative incidence functions (CIFs) were compared using Gray’s test. Results: Among 3,009 women with pure DCIS treated with BCS, 1,562 (52%) received RT. Median age at diagnosis was 56 years in the RT group and 62 years in the non-RT group. Median follow-up was 22.4 years for those who received RT and 21.2 years for those who did not. On multivariable analyses adjusting for age and history of heart disease, RT was not associated with a significant increase in the risk of AMI (HR 1.13, 95% CI 0.84-1.53, p=0.43), coronary revascularization (HR 1.33, 95% CI 0.95-1.88, p=0.10), death due to IHD (HR 0.89, 95% CI 0.51-1.55, p=0.68), or the composite outcome (HR 1.09, 95% CI 0.85-1.41, p=0.49). At 20 years, the cumulative incidence of AMI was 5.0% with RT vs 5.9% without RT (p=0.39); coronary revascularization was 4.6% vs 4.0% (p=0.26); and death due to IHD was 1.7% vs 3.7% (p=0.0006). The 20-year cumulative incidence of the composite cardiac outcome was 7.1% with RT vs 7.7% without RT (p=0.04). When stratified by laterality, there were no significant differences in 20-year incidence of AMI (4.6% left vs 5.4% right, p=0.68), IHD death (1.6% vs 1.7%, p=0.85), or the composite event (7.1% vs 7.0%, p=0.95). Conclusions: In this large, population-based cohort of women with pure DCIS treated with BCS, whole-breast RT, including to the left breast, was not associated with increased risk of long-term cardiac events after over two decades of follow-up. These findings support the cardiac safety of contemporary breast RT techniques in the management of DCIS and should be considered when weighing the risks and benefits of adjuvant RT.

C. Pisano¹, Y. Sun², C. Speers³, A. Amin⁴, C. Shah⁵, A. Montero⁶, P. Li⁴, A. Simpson⁴, L. Rock⁴, M. Miller⁴, R. Tendulkar⁷, J. Lyons¹; ¹Radiation Oncology, Case Western Reserve University/University Hospitals Cleveland Medical Center, Cleveland, OH, ²Biostatistics, Case Western Reserve University, Cleveland, OH, ³Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL, ⁴Breast Surgery, Case Western Reserve University/University Hospitals Cleveland Medical Center, Cleveland, OH, ⁵Radiation Oncology, Allegheny Health Network, Pittsburg, PA, ⁶Medical Oncology, Case Western Reserve University/University Hospitals Cleveland Medical Center, Cleveland, OH, ⁷Radiation Oncology, Cleveland Clinic Foundation, Cleveland, OH.

Introduction: Over the last three decades, breast cancer survival rates have continued to improve, leading to higher rates of ipsilateral breast events. Many patients prefer to avoid mastectomy, increasing interest in repeat breast-conserving surgery (BCS). The current standard for partial breast re-irradiation is twice daily treatments based on the results of RTOG 1014, which can be burdensome for patients. This study was designed to assess the feasibility, toxicity, and efficacy of daily hypofractionated external beam partial breast re-irradiation following repeat BCS. The primary endpoint is the rate of grade 3+ treatment-related skin, fibrosis, and breast pain adverse events at one-year post-reirradiation, graded by CTCAE criteria. Here, we report preliminary findings.Methods: This is a currently open multicenter, single-arm prospective phase II trial of patients previously treated with breast-conserving surgery (BCS) and adjuvant radiation therapy (all forms eligible). At the time of enrollment, all patients had a unifocal in-breast tumor recurrence or new primary histologically confirmed invasive ductal carcinoma or DCIS, measuring less than 3 cm with negative margins defined as no tumor on ink after repeat BCS. Patients received 40.05 Gy in 15 daily fractions of 2.67 Gy. For patients with high-risk features (young age, poor biology, close margins, high grade), felt to benefit from a boost, an SIB to a smaller margin of 48 Gy was delivered. Follow-up data and patient surveys are collected at 1, 3, 6, 9, 12 months and 3 years. Overall cosmesis is evaluated at 1 and 3 years using the BCTOS quality of life questionnaire (ePRO), the Global Cosmesis Score (ePRO), and the Worksheet for Breast Condition (ePRO).Results: Between October 2023 and June 2025, 16 patients were screened, and 13 were enrolled. Among the 3 patients who declined enrollment, 2 opted for treatment at a facility closer to home that did not support clinical trial participation, while 1 was deemed ineligible. All three received daily fractionated treatment off protocol. One enrolled patient withdrew consent prior to initiating treatment. Ten patients completed treatment and reached the 30-day follow-up mark. Of these, 9 had baseline cosmetic assessments: 11% reported excellent cosmesis, 44% good, 22% fair, and 22% poor. At 30 days, 10 patients had follow-up cosmetic evaluations: 10% reported excellent cosmesis, 60% good, and 30% fair. No patients reported worsening cosmetic outcomes at 30 days, and 3 showed improvement. All patients expressed complete satisfaction with their overall treatment experience. Treatments were well tolerated, with no grade 3 acute adverse events related to therapy. No cases of skin desquamation were observed post-reirradiation. Of the 5 patients who reported mild breast pain at 1 month, all had experienced pain at baseline. With regards to acute toxicity, 6 patients developed grade 1 radiation dermatitis, all of which resolved following treatment. Conclusion: To date, the trial has demonstrated strong patient interest and acceptance, with treatment being well-tolerated. No acute Grade 3 adverse events have been observed and all patients expressed overall satisfaction with the treatment experience. If outcomes are comparable to the current standard of care, this approach may provide a more convenient alternative and potentially improve acceptance of repeat breast-conserving therapy. Longer-term follow-up will be necessary to evaluate late cosmetic outcomes, chronic adverse events and efficacy.