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) for germline pathogenic variant (GPVs) carriers were historically performed as total mastectomy (TM) or skin-sparing mastectomy (SSM), although nipple-sparing mastectomy (NSM) has recently emerged as an oncologically safe RRM option. Methods This retrospective cohort study included all female patients with confirmed BRCA1 , BRCA2 , PALB2 , or other high-penetrance GPVs at two academic institutions in Canada between 2003 and 2024. Temporal trends in NSM uptake were assessed using the Mantel-Haenszel test for trend and multivariable logistic regression. Results After exclusions, 559 GPV carriers including 319 (57%) affected carriers and 240 (43%) unaffected carriers comprised the study cohort. The median age at RRM was 45 years old (range 22–76) and most were BRCA1 carriers (46.7%) or BRCA2 carriers (44.4%). Overall, 310 carriers (55.5%) underwent NSM, 174 (31.1%) underwent SSM, and 75 (13.4%) underwent TM. NSM uptake was highest among patients aged 40–49 years (56%) and lowest in those ≥ 60 years (42%, p = 0.03). Relative to unaffected carriers, affected carriers (47% vs. 66%, p < 0.001) and those with prior radiation were less likely to undergo NSM (34.3% vs. 62.7%, p < 0.001). A clear increase in NSM occurred over time, from 11.9% pre-2012 to 74.4% after 2022 ( p < 0.001). Multivariable analysis adjusting for age, GPV, parity, menopausal status, and personal history of breast cancer identified normal BMI (OR 1.99, 95% CI 1.18–3.34), lack of radiation exposure (OR 3.03, 95% CI 1.76–5.23), and year of surgery as independent predictors of NSM receipt (OR 1.25, 95% CI 1.19–1.32). Conclusion There has been a significant increase in NSM use among BRCA1/2 , PALB2 and other GPV carriers over the last two decades.