Tamoxifen use and risk of endometrial cancer in breast cancer patients: A systematic review and dose–response meta‐analysis

Background Worse prognosis of endometrial cancers (EC) in tamoxifen‐treated women compared to non‐tamoxifen‐treated women been proposed. The relationship between tamoxifen treatment of breast cancer (BC) and the risk of EC is controversial and there is no agreement between publication results on this issue (the answer to all comments provided in the page 2 of manuscript). The aim of this study is investigation the association between tamoxifen treatment and the risk of EC in patients with BC. Methods and Results We conducted a comprehensive search with related keywords in MEDLINE/PubMed, SCOPUS, and Web of Science databases until April 16, 2022. Random‐effects model (DerSimonian and Laird) was used to pool risk ratios (RRs) with 95% confidence intervals (CIs) of EC. Dose, cumulative dose, and duration‐response analysis were performed in linear and non‐linear states. Twenty‐six studies reported a relation between tamoxifen treatment and risk of EC in patients with BC. Results showed a direct relationship between tamoxifen use and EC (RR: 2.03, 95% CI: 1.68–2.45; I2:76%). By increase the age of participants, the risk of EC was decrease (coef = −.0206), although this was not statistically significant (p = .37). Linear dose–response model indicated a direct significant association between dose and duration use of tamoxifen and EC (dose: exe(b) = 1.019, p = .001; duration: exe(b) = 1.014, p = .001). Non‐linear dose–response analysis confirmed linear analysis. Conclusion This study highlights that tamoxifen use is a significant risk factor related to the incidence of EC in patients with BC.