IMPACT OF BRCA1 AND BRCA2 GENE MUTATIONS ON BREAST AND OVARIAN CANCER PREVENTION STRATEGIES
DOI:
https://doi.org/10.71000/69n38822Keywords:
BRCA1; BRCA2; Hereditary Breast and Ovarian Cancer; Risk-Reducing Surgery; Magnetic Resonance Imaging; Systematic Review.Abstract
Background: Pathogenic mutations in the BRCA1 and BRCA2 genes significantly elevate lifetime risks for breast and ovarian cancers, necessitating specialized prevention strategies. Despite established guidelines, the rapid evolution of evidence on the efficacy and impact of various risk-management options—including surgery, enhanced surveillance, and chemoprevention—requires continual synthesis to inform clinical practice.
Objective: This systematic review aimed to synthesize contemporary evidence on how BRCA1/2 gene mutations influence and justify specific prevention, screening, and management strategies for breast and ovarian cancers.
Methods: A systematic review was conducted following PRISMA guidelines. A comprehensive search of PubMed/MEDLINE, Scopus, Embase, and the Cochrane Library was performed for studies published between 2019-2024. Inclusion criteria focused on comparative studies of BRCA1/2 carriers evaluating prevention interventions (risk-reducing surgery, intensive surveillance, chemoprevention) against relevant comparators, with outcomes including cancer incidence, mortality, and quality of life. Study selection, data extraction, and risk-of-bias assessment using the Newcastle-Ottawa Scale and Cochrane RoB 2 tool were performed independently by two reviewers. A narrative synthesis was undertaken due to clinical heterogeneity.
Results: Eight studies (n=12,548 carriers) were included. Risk-reducing salpingo-oophorectomy was associated with an 80-88% reduction in ovarian cancer risk and improved all-cause mortality. Risk-reducing mastectomy reduced breast cancer risk by >90%. Annual breast MRI with mammography significantly outperformed mammography alone, with higher sensitivity (93% vs. 42%) and lower interval cancer rates. Evidence for chemoprevention was less robust. Studies highlighted the importance of incorporating quality-of-life and psychosocial outcomes into decision-making.
Conclusion: For BRCA1/2 carriers, risk-reducing surgeries and MRI-enhanced surveillance are highly effective strategies for cancer risk reduction and early detection. Optimal care requires a personalized, shared decision-making approach that balances oncologic efficacy with personal values and psychosocial well-being. Further research is needed on long-term quality of life and novel preventive agents.
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Copyright (c) 2025 Muhammad Numair Kashif, Aasma Sajawal, Nishwa Ali, Mah Rukh Fayyaz, Farhat R. Malik, Muhammad Adnan , Syeddah Saiqa Gillani, Akif Saeed Ch (Author)
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