Safety and Efficacy Profile of Tamoxifen for the Prevention of BreastCancer: Systematic Review and Meta-Analysis

Introduction: The U.S. Food and Drug Administration (FDA) approved tamoxifen in 1977 for the prevention of breast cancer. Tamoxifen is effective against hormone receptor– positive breast cancer; however, its long-term safety in prevention settings continues to be evaluated. Method: We systematically searched PubMed, ScienceDirect, and Embase through April 2024 to identify eligible articles for the current study. Randomized Controlled Trials (RCTs) comparing tamoxifen with a comparator in healthy women or women at increased risk of breast cancer (≥18 years) were included in this Systematic Review and Meta-Analysis (SRMA). The Risk of Bias tool 2 (ROB2) was used to evaluate the quality of the included studies Results: Out of 286 articles, 6 RCTs met the inclusion criteria. Tamoxifen significantly reduced the risk of invasive breast cancer (RR=0.74, 95% CI: 0.67-0.83, p < 0.01) and ER-positive breast cancer (RR=0.65, 95% CI: 0.58-0.73, p < 0.01). Increased risks were noted for endometrial cancer (RR=2.13, 95% CI: 1.50-3.04) and thromboembolic events (RR=1.48, 95% CI: 1.21-1.80). Discussion: Tamoxifen significantly reduces the risk of invasive and ER-positive breast cancer, reinforcing its efficacy as a preventive therapy for high-risk women. However, it is associated with increased risks of endometrial cancer and thromboembolic events, requiring careful patient monitoring. Conclusion: Tamoxifen remains a preventive option for high-risk women, with benefits primarily in ER-positive disease. Careful monitoring is warranted given the increased risks of endometrial cancer and thromboembolism. Further work should optimize dose, duration, and patient selection and evaluate long-term safety across diverse populations.