Endometrial effect of hormone therapy in patients with breast cancer: a multicentre retrospective study

Tamoxifen has an estrogenic effect on the endometrium and increases the risk of benign and malignant uterine pathologies in breast cancer patients. Therefore, newer endocrine therapies antagonise by either blocking estrogen receptors or inhibiting estrogen production such as gonadotrophin-releasing hormone agonist (GnRH agonist) and aromatase inhibitors (Ais) have been compared to tamoxifen. Ais have less effect on uterine pathologies and even decrease endometrial thickness. This study is to compare factors associated with proven endometrial pathology associated with hormone therapy in breast cancer patients. A total of 425 women with a diagnosis of breast cancer, who had suspected endometrial changes by transvaginal ultrasound (TVS) were reviewed at 11 institutions in South Korea from January 2016 to December 2021. Clinical characteristics and the result of endometrial assessment were compared between women with no adjuvant hormone therapy, tamoxifen therapy, tamoxifen with GnRH-agonist therapy, and tamoxifen with Ais therapy. Endometrial pathology (atypical endometrial hyperplasia and cancer) was diagnosed in 23 patients (0.05%). Seventeen women (6.5%) were diagnosed with endometrial pathology in tamoxifen group, 2 patients (2.6%) in tamoxifen with GnRH-agonist group, and 1 patient (2.4%) in tamoxifen with Ais group. There were significant difference in the endometrial thickness ≥ 8, 10, 12 mm between groups (P < 0.001). Of the 186 patients (71.0%) within the tamoxifen group, 37 patients (47.4%) in the tamoxifen with GnRH-agonist group, and 5 patients (12.2%) in the tamoxifen with Ais group were presented with an endometrial thickness ≥ 8mm. Significantly fewer endometrial pathology was revealed in tamoxifen with GnRH-agonist and Ais group. In addition, adding GnRH-agonist or Ais treatment significantly reduced the thickening of the endometrium in breast cancer patients with tamoxifen-induced endometrial abnormalities. Avoiding invasive procedures can be one of the potential benefits of adding GnRH agonist or Ais.