Alwashmi Ameen S S, Khan Najeeb Ullah, Chen Tianhui
Department of Medical Laboratories, College of Applied Medical Sciences, Qassim University, Buraydah, Qassim, 51452, Saudi Arabia.
Institute of Biotechnology & Genetic Engineering (Health Division), The University of Agriculture, Peshawar, 25130, Pakistan.
Sci Rep. 2025 Feb 25;15(1):6796. doi: 10.1038/s41598-025-89915-z.
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.
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).
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.
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.
乳腺癌是一项重大的全球健康负担，诸如BRCA1/2突变等遗传因素会显著增加终生患病风险。本荟萃分析旨在评估选择性雌激素受体调节剂（SERM）他莫昔芬和雷洛昔芬作为化学预防药物在降低BRCA1/2突变携带者患乳腺癌风险方面的效果。
根据PRISMA指南进行荟萃分析。检索了PubMed、Cochrane图书馆和MEDLINE数据库，以查找2000年至2024年期间发表的相关研究。纳入了检查BRCA1/2携带者使用他莫昔芬/雷洛昔芬情况的病例对照研究和观察性队列研究。还提取了乳腺癌发病率和风险比的数据。使用纽卡斯尔-渥太华量表（NOS）评估质量。使用Review Manager（版本5.4.0）进行随机效应荟萃分析。
纳入了9项研究（13676名女性）。根据NOS清单评估，两项研究风险较低，其余7项研究风险中等。汇总分析显示，与对照组相比，他莫昔芬/雷洛昔芬降低了患乳腺癌的风险（风险比0.80，95%置信区间0.72 - 0.88，p = 0.04）。使用他莫昔芬后，BRCA1/2携带者中乳腺癌发病的风险比降低（风险比1.82，95%置信区间1.48 - 2.23，p < 0.00001）。亚组分析显示，在BRCA1携带者（风险比1.51，95%置信区间1.48 - 1.51）和BRCA2携带者（风险比1.48，95%置信区间1.40 - 1.58）中，使用SERM均降低了患乳腺癌的风险。异质性范围为51%至85%，表明不同纳入研究背后的真实效应大小具有高度显著性和变异性。而BRCA1和BRCA2亚组之间的异质性为98%，差异为0%，表明在降低乳腺癌风险方面对SERM的反应无差异。
本荟萃分析提供了证据，表明他莫昔芬和雷洛昔芬可显著降低BRCA1/2突变女性患乳腺癌的风险。BRCA1和BRCA2携带者的化学预防效果相似。需要进一步研究来验证这些发现，并优化其在高危人群中的使用。
