Abstract
PURPOSE: To report the rates of risk-reducing surgery (RRS) following germline testing for BRCA1/2 (likely) pathogenic variants (BRCApv) and to assess the impact of RRS and BRCA status on survival after surgical treatment for unilateral breast cancer (BC). METHODS: We identified 7145 women with BC (2000-2017), a BRCA test and median follow-up of 10.8 years from the Danish Breast Cancer Cooperative Group's clinical database. Distant recurrence-free (DRFS) and overall survival (OS) according to BRCA status were evaluated using the Kaplan-Meier method. Hazard ratios (HR) for BRCApv vs. BRCA wild-type, contralateral risk-reducing mastectomy (CRRM), and risk-reducing bilateral salpingo-oophorectomy (RRBSO), including interaction tests, were estimated using multivariable Cox models. RESULTS: Among BRCA1pv carriers (n = 403), CRRM rates were higher than in BRCA2pv (n = 317) (66% vs. 52%, p < 0.001) and more likely to receive timely testing, i.e., within 6 months of BC diagnosis (75% vs. 52%, p = 0.004). Regarding RRBSO rates, no differences were observed. CRRM was associated with significantly improved DRFS (HR = 0.63, 95% CI 0.51-0.78) and OS (HR = 0.64, 95% CI 0.51-0.82), independently of BRCA status and age. RRBSO was associated with improved OS only in BRCApv carriers, specifically, those aged ≥ 50 years (HR = 0.44, 95% CI 0.26-0.75). BRCApv (irrespective of affected gene) was associated with worse DRFS (HR = 1.31, 95% CI 1.06-1.63); however, this was only evident after 2 years of follow-up (HR = 1.53, 95% CI 1.22-1.93). BRCApv was not significantly associated with worse OS (HR = 1.25, 95%CI 0.98-1.58). CONCLUSION: Timely germline testing at BC diagnosis might increase CRRM rates in BRCApv carriers, thereby improving survival.