Role of GPR30 in endometrial pathology after tamoxifen for breast cancer

OBJECTIVE: This study was undertaken to evaluate the potential role of G-protein-coupled estrogen receptor in endometrial pathology associated with tamoxifen treatment of breast cancer patients. STUDY DESIGN: We investigated whether G-protein-coupled estrogen receptor plays a role in mediating proliferating effect of tamoxifen in endometrial carcinoma cells. These results were compared with the G-protein-coupled estrogen receptor expression pattern in endometrial tissue from a cohort of 95 breast cancer patients, who received tamoxifen or another adjuvant therapy. RESULTS: In vitro tamoxifen significantly stimulated the mitogen-activated protein kinase phosphorylation and cell proliferation of endometrial cell lines via G-protein-coupled estrogen receptor. In vivo, there was a significant correlation between G-protein-coupled estrogen receptor expression and the tamoxifen-induced endometrial pathology (P = .006). Moreover, G-protein-coupled estrogen receptor positivity was predictive of an earlier development of symptoms, such as bleeding or suspect endometrial thickness, induced by tamoxifen therapy (P = .019). CONCLUSION: G-protein-coupled estrogen receptor plays an important role in tamoxifen-induced endometrial abnormalities.