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.