Does bilateral mastectomy affect clinical outcomes in BRCA1/2 mutation carriers with primary breast cancer? A systematic review and meta-analysis.

BACKGROUND: BRCA1/2-carriers—who account for 5–10% of breast cancer (BC) cases—face markedly elevated lifetime risks of BC. Among those diagnosed with primary breast cancer (PBC), these carriers confront a cumulative contralateral breast cancer (CBC) risk of 40% within 10 years—alongside poorer overall survival (OS) and breast cancer–specific survival (BCSS). Whether contralateral risk-reducing mastectomy (CRRM) can improve OS, BCSS, and reduce CBC risk in this high-risk group remains unresolved. PATIENTS AND METHODS: We conducted a systematic review and meta-analysis of cohort studies (PROSPERO:CRD420251024265). PubMed, Embase, Cochrane Library were searched through June 2025. Studies enrolled BRCA1/2-carriers with PBC, compared CRRM versus Non-CRRM, and reported OS, BCSS, or CBC risk. We pooled hazard ratio (HR) and risk ratio (RR) for these outcomes. Heterogeneity was quantified by I2. RESULTS: This meta‐analysis included nine cohort studies, encompassing BRCA1/2-carriers with PBC. In the OS analysis, including 3138 patients in the CRRM group versus 2,592 in the Non-CRRM group, CRRM presented a substantial survival benefit (HR 0.638; P < 0.001). BCSS (567 CRRM and 623 Non-CRRM patients), likewise demonstrated an advantage for the CRRM group (HR 0.601; P = 0.005). CBC risk, evaluated in 637 CRRM and 976 Non-CRRM patients, was reduced by 91% (RR 0.090; P < 0.001), reflecting an absolute risk reduction of 188 CBC events per 1000. CONCLUSION: CRRM confers substantial oncologic benefits, improving OS and BCSS and reducing CBC risk in BRCA1/2 carriers with PBC, and should be considered for this high-risk population, informing guideline recommendations.