Abstract
BACKGROUND: Nipple-sparing mastectomy (NSM) is a surgical option offering both oncological safety and cosmetic benefits. However, the oncological safety of NSM in carriers of BRCA1/2 pathogenic variants/likely pathogenic variants (PV/LPV) with breast cancer and the role of risk-reducing mastectomy remain underexplored, especially in Asian populations. This study evaluated the safety and effectiveness of NSM in BRCA1/2 PV/LPV carriers and assessed the preventive impact of contralateral risk-reducing NSM (RRNSM) on cancer incidence. METHODS: This multicentre retrospective study included women aged 20-80 years who underwent NSM for therapeutic or risk-reducing purposes and received germline BRCA1/2 tests between May 2006 and June 2022 across 19 institutions in Korea. Patients with distant metastasis at diagnosis were excluded. Information on demographics, the clinical characteristics of patients and tumours, surgical details, and follow-up outcomes was collected from a review the medical records of each participating institution. The primary outcome was the oncological safety of NSM, assessed by comparing ipsilateral local recurrence rates between patients with and without BRCA1/2 PV/LPV. The secondary outcome was cancer incidence in patients who underwent contralateral RRNSM versus those who did not. RESULTS: In all, 787 women underwent 906 NSMs, with a median (interquartile range) follow-up of 59.3 (44.0-82.8) months. Among the participants, 186 (23.6%) were BRCA1/2 PV/LPV carriers. Ipsilateral local recurrence rates were comparable between BRCA1/2 PV/LPV carriers and non-carriers (6.4 versus 7.4%, respectively). The 5-year local recurrence-free survival rates did not differ significantly between BRCA1/2 PV/LPV carriers and non-carriers (92.2% versus 93.2%, respectively; P = 0.87). Contralateral breast cancer occurred in 4.5% of patients with BRCA1/2 PV/LPV who did not undergo contralateral RRNSM, whereas no cases of contralateral breast cancer were reported among patients who underwent RRNSM regardless of BRCA1/2 status. CONCLUSIONS: This study highlights NSM as a safe and effective surgical option for BRCA1/2 PV/LPV carriers with breast cancer, as well as a risk-reducing strategy. Further prospective studies are needed to confirm these findings and evaluate long-term outcomes.