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<p>Background: Breast cancer is a major global health burden, with hereditary factors such as <i>BRCA1/2</i> 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 <i>BRCA1/2</i> 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 <i>BRCA1/2</i> 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, <i>p</i> = 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, <i>p</i> &lt; 0.00001). Subgroup analysis revealed reduced breast cancer risk with SERM use in both <i>BRCA1</i> (RR 1.51, 95% CI 1.48–1.51) and <i>BRCA2</i> 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 <i>BRCA1</i> and <i>BRCA2</i> 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 <i>BRCA1/2</i> mutations. Chemoprevention efficacy was similar for both <i>BRCA1</i> and <i>BRCA2</i> carriers. Further research is needed to validate these findings and to optimize their use in high-risk populations.</p>

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

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  • 发表日期：

    2025年2月25日

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  • Ameen S. S. Alwashmi,
  • Najeeb Ullah Khan,
  • Tianhui Chen

摘要

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.