Secondary Risk-Reducing Strategies for Contralateral Breast Cancer in BRCA1/2 Variant Carriers: A Systematic Review and Meta-analysis.

Introduction: Breast cancer poses significant challenges, especially the increased risk of contralateral breast cancer (CBC) in BRCA1/2 variant carriers. This study systematically reviews and analyzes the effectiveness of secondary risk-reducing strategies for CBC in BRCA1/2 carriers.

Methods: A systematic review and meta-analysis were conducted from January 2000 to December 2023, including RCTs, cohort, or case-control studies involving BRCA carriers with unilateral breast cancer. Random-effects models were used for odds ratios (ORs) on CBC incidence and hazard ratios (HRs) for overall survival (OS), with bias assessed via the Newcastle-Ottawa Scale.

Results: A total of 23,840 participants from 26 studies were included. Secondary risk-reducing interventions reduced CBC incidence by 38% [OR 0.62, 95% confidence interval (CI) 0.57-0.68] and improved OS by 45% (HR 0.55, 95% CI 0.46-0.67). Subgroup analyses showed differences by BRCA type, menopausal status, and treatment duration. For BRCA1 carriers, chemotherapy was most effective, while, for BRCA2, it was endocrine therapy. Postmenopausal interventions reduced CBC by 47% (OR 0.53, 95% CI 0.40-0.71), while premenopausal carriers saw a 34% reduction (OR 0.66, 95% CI 0.53-0.82). Tamoxifen's effect diminished over time.

Conclusion: Secondary prophylaxis reduces CBC and improves OS in BRCA1/2 carriers, with variations by genetic and physiological factors. These findings underscore the need for personalized strategies, considering menopausal status and treatment duration.