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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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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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Journal Article
Risk-benefits assessment of tamoxifen or raloxifene as chemoprevention for risk reduction of breast cancer among BRCA1 and BRCA2 carriers: a meta-analysis
2025
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 631/61
/ 631/67
/ BRCA1/2
/ Breast Neoplasms - drug therapy
/ Breast Neoplasms - prevention & control
/ Cancer
/ Female
/ Humanities and Social Sciences
/ Humans
/ Mutation
/ Raloxifene Hydrochloride - therapeutic use
/ Science
/ Selective estrogen receptor modulators
