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Meta-Analysis
. 2025 Feb 25;15(1):6796.
doi: 10.1038/s41598-025-89915-z.

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

Ameen S S Alwashmi  1 , Najeeb Ullah Khan  2 , Tianhui Chen  3
Affiliations
Meta-Analysis

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

Ameen S S Alwashmi et al. Sci Rep. .

Abstract

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.

Keywords: BRCA1/2; Breast cancer; Chemoprevention; Raloxifene; Selective estrogen receptor modulators; Tamoxifen.

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Conflict of interest statement

Declarations. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Screening and selection of included studies by PRISMA Guidelines.
Fig. 2
Fig. 2
Forest plot of Risk ratio of breast cancer incidence among tamoxifen or raloxifene and control.
Fig. 3
Fig. 3
Funnel plot of Risk ratio of breast cancer incidence among tamoxifen or raloxifene and control.
Fig. 4
Fig. 4
Forest plot of the risk ratio of breast cancer among BRCA1/2 carriers.
Fig. 5
Fig. 5
Funnel plot of the risk ratio of breast cancer among BRCA1/2 carriers.
Fig. 6
Fig. 6
Forest plot of the risk ratio of breast cancer incidence among BRCA1 and BRCA2 subgroups.
Fig. 7
Fig. 7
Funnel plot of the risk ratio of breast cancer among BRCA1 and BRCA2 risk ratio.
See this image and copyright information in PMC

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