Abstract PS3-02-01: Trends in the uptake of nipple-sparing mastectomy in BRCA1/2, PALB2 and other pathogenic variant carriers undergoing risk reducing mastectomy

Abstract Introduction: Risk-reducing mastectomy (RRM) a well-established preventive intervention in germline pathogenic variants (GPVs) carriers. Historically, RRMs were performed as total mastectomy (TM) or skin-sparing mastectomy (SSM), although nipple-sparing mastectomy (NSM) has recently emerged as a RRM option. In this study, we assessed temporal trends in NSM uptake. Methods: This retrospective cohort study included all female patients with confirmed BRCA1, BRCA2, PALB2, or other GPVs carriers at two academic institutions in Montreal, Canada, between 2003 and 2024. The primary outcome was the proportion of GPV carriers NSM compared to SSM and TM over time as evaluated by Mantel Haenszel test for trend. Results: After exclusions, 441 GPV carriers were included in the cohort, 260 (59%) affected carriers and 181 (41%) unaffected carriers. The median age at RRM was 44 years old (range 22-76). Most were BRCA1 carriers (45.5%) or BRCA2 carriers (44.8%) while the remaining 9.8% were PALB2 and other GPV carriers. Overall, 269 (61%) underwent NSM, 118 (26.8%) underwent SSM, and 54 (12.2%) underwent TM. NSM uptake was highest among patients aged 40-49 years (68.6%) and lowest in those ≥60 years (45.8%, p=0.04). Relative to affected carriers, unaffected carriers were more likely to undergo NSM (72.4%, Vs.53.1% p<0.001). Prior radiation significantly decreased the likelihood of NSM (38.4% vs. 68.7%, p<0.001). A clear increase in NSM occurred over time, from 12.5% of GPV carriers pre-2012 to 77.5% after 2022 (p<0.001). Multivariable analysis adjusting for age, GPV, personal history of breast cancer and prior radiation identified year of surgery as the strongest predictor of NSM (OR 28.9, 95% CI 10.1-77.0) post-2019 compared to pre-2012 (p<0.001). Conclusion: There has been a significant increase in NSM uptake among GPV carriers over the last two decades. Understanding these trends supports informed decision-making and standardization of preventive care in high-risk populations. Citation Format: M. Alsuhaibani, A. Melanson, A. Viezel-Mathieu, T. Dionisopoulos, M. Basik, J. Boileau, M. Martel, I. Prakash, S. Meterissian, J. Vorstenbosch, W. Foulkes, S. Wong. Trends in the uptake of nipple-sparing mastectomy in BRCA1/2, PALB2 and other pathogenic variant carriers undergoing risk reducing mastectomy [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS3-02-01.