Beyond breast cancer: role of selective estrogen receptor modulators in reducing systemic malignancies: evidence from population-based data

Background: Raloxifene and bazedoxifene are selective estrogen receptor modulators (SERMs) used to prevent and treat osteoporosis in postmenopausal women. Raloxifene is also known for its preventive effect against invasive breast cancer; however, its effect on other cancer types is unclear. This study investigated the incidence of various cancers in osteoporosis patients receiving SERM therapy to determine its association with the risk of developing specific cancer types. Methods: This retrospective cohort study examined the association between SERM use and the incidence of cervical, endometrial, ovarian, and colorectal cancers in postmenopausal women using data from the Korean National Health Insurance Service. Propensity score matching ensured group comparability by analyzing 95,513 participants. Cox proportional hazard models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to assess the cancer risk associated with SERM therapy, differentiating between the effects of raloxifene and bazedoxifene. Results: SERM therapy was associated with a reduced risk of cervical (adjusted HR = 0.47, 95% CI = 0.31–0.71), ovarian (adjusted HR = 0.61, 95% CI = 0.42–0.88), and colorectal cancer (adjusted HR = 0.49, 95% CI = 0.42–0.57). No significant risk reduction was observed for endometrial cancer (adjusted HR = 1.05, 95% CI = 0.70–1.59). A comparison between raloxifene and bazedoxifene revealed no significant differences in their cancer prevention effects. Conclusion: SERM therapy administration is associated with a decreased incidence of cervical, ovarian, and colorectal cancers. Notably, the effects of raloxifene and bazedoxifene were consistent. Further investigations are crucial to elucidate the mechanisms underlying these observations and their clinical implications.