Adjuvant treatment with tamoxifen for estrogen receptor-positive breast cancer and gynecological risks in premenopausal and perimenopausal women – a systematic review

Tamoxifen (TMX) is known to increase the risk of endometrial cancer (EC) in postmenopausal women, but data on the effects in premenopausal and perimenopausal women remain inconsistent and not well illuminated. This study aimed to evaluate whether TMX increases the risks of gynecological symptoms and EC in premenopausal and perimenopausal women receiving adjuvant therapy for estrogen receptor-positive breast cancer. Systematic searches in PubMed, Cochrane and Web Of Science yielded 319 relevant articles, of which 38 were analyzed after excluding duplicates and non-qualifying studies. The Oxford Criteria were used to ensure consistent evaluation before final inclusion. No meta-analysis was conducted due to study heterogeneity. Ten studies (two meta-analyses, one systematic review, four retrospective cohort studies, one retrospective comparative study, one prospective cohort study and one case–control study) were included. TMX was associated with an increased risk of EC in premenopausal and perimenopausal women (mean relative risk 2.25; standard deviation 0.9) compared to no treatment or treatment with raloxifene or aromatase inhibitors. Risk appeared in some studies to increase with treatment duration and persisted for ≥5 years post treatment. TMX also significantly increased the risk of gynecological symptoms, benign and premalignant endometrial pathology, intrauterine procedures and hysterectomy (<i>p</i> &lt; 0.001). TMX seems to increase EC risk and significantly increase the risk of gynecological symptoms in premenopausal and perimenopausal women, with risk persisting years following treatment cessation. Healthcare professionals should counsel these women on potential risks and emphasize prompt evaluation of gynecological symptoms. Tamoxifen; breast cancer; endometrial cancer; gynecological symptoms; premenopausal; perimenopausal; systematic review