Risk-benefits assessment of tamoxifen or raloxifene as chemoprevention for risk reduction of breast cancer among BRCA1 and BRCA2 carriers: a meta-analysis.

BACKGROUND

Breast cancer is a major global health burden, with hereditary factors such as BRCA1/2 mutations significantly increasing the lifetime risk. This meta-analysis aimed to evaluate the outcomes of selective estrogen receptor modulators (SERMs), tamoxifen, and raloxifene as chemopreventive agents for breast cancer risk reduction in BRCA1/2 mutation carriers.

METHODS

A meta-analysis was conducted according to the PRISMA guidelines. PubMed, Cochrane Library, and MEDLINE databases were searched for relevant studies published between 2000 and 2024. Case-control studies and observational cohort studies examining the use of tamoxifen/raloxifene in BRCA1/2 carriers were included. Data on the incidence and risk ratios of breast cancer were also extracted. Quality was assessed using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis was performed using Review Manager (version 5.4.0).

RESULTS

Nine studies (13,676 women) were included. Two studies had low risk, and the remaining seven studies had moderate risk, as assessed by the NOS checklist. Pooled analysis showed tamoxifen/raloxifene decreased breast cancer risk compared to controls (RR 0.80, 95% CI 0.72-0.88, p = 0.04). The risk ratio of breast cancer incidence among BRCA1/2 carriers was reduced after tamoxifen use (RR 1.82, 95% CI 1.48-2.23, p < 0.00001). Subgroup analysis revealed reduced breast cancer risk with SERM use in both BRCA1 (RR 1.51, 95% CI 1.48-1.51) and BRCA2 carriers (RR 1.48, 95% CI 1.40-1.58). The heterogeneity ranged from 51 to 85%, representing high significance and variation in true effect sizes underlying the different included studies. Whereas the heterogeneity among subgroups BRCA1 and BRCA2 was 98%, and the difference was 0%, showing no difference in response to SERM for risk reduction of breast cancer.

CONCLUSION

This meta-analysis provides evidence that tamoxifen and raloxifene significantly reduce the breast cancer risk in women with BRCA1/2 mutations. Chemoprevention efficacy was similar for both BRCA1 and BRCA2 carriers. Further research is needed to validate these findings and to optimize their use in high-risk populations.