Endometrial pathologies in tamoxifen-treated breast cancer patients

Lee, Kyung Eun; Ko, Young Bok; Noh, Heung Tae; Suh, Kwang Sun

Abstract

OBJECTIVE
Tamoxifen is a nonsteroidal hormone that functions as a selective estrogen-receptor (ER) modulator in breast tissue. It is the first-choice drug for the postoperative treatment of ER-positive breast cancer patients. However, tamoxifen, if administered for a prolonged duration, has estrogen-like effects on the uterus, leading to an increased risk for the development of endometrial diseases such as endometrial hyperplasia, endometrial polyp, and endometrial cancer. This study was designed to investigate the effects of tamoxifen treatment on endometrium in breast cancer patients.
METHODS
Fifty-five tamoxifen-treated breast cancer patients visited an outpatient gynecology clinic. We analyzed the endometrial pathology with consideration to the duration of tamoxifen treatment the patient symptoms and the endometrial thickness, as measured by transvaginal ultrasonography. Endometrial polypectomy was performed to obtained polyps from women presenting with abnormal bleeding (17 polyps from postmenopausal women who had not been treated with tamoxifen and 14 from women who had been treated with this drug). To investigate the effects of tamoxifen treatment on the endometrial polyps, we performed immunohistochemical staining for ER, the progesterone receptor (PR), and Ki67 on the polyps obtained from both groups of women.
RESULTS
In 29 (52.7%) of 55 tamoxifen-treated breast cancer patients, the endometrium was more than 10 mm thick, and in 19 (65.5%) of these patients, the abnormalities noted comprised 11 endometrial polyps, 5 endometrial carcinomas, 2 submucosal myomas, and 1 endometrial hyperplasia. The incidence of endometrial proliferation was significantly higher in patients who had been treated with tamoxifen for less than 1 year (P=0.037) than in those who had been treated for more than 1 year. Although the endometrial carcinomas, submucosal myomas, and endometrial hyperplasia were found in the patients who had been treated for more than 1 year, this result was not statistically significantwhen compared with the other group. As compared to the endometrial polyps obtained from women who had not received tamoxifen treatment, those obtained from patients who had received the treatment exhibited significantly lower levels of ER expression (P=0.000) in the glands and increased levels of PR (P=0.031) and Ki-67 expression (P=0.000) in the stroma.
CONCLUSIONS
During tamoxifen treatment for breast cancer, the endometrial pathology should be investigated if transvaginal ultrasonography reveals the tissue to be more than 10 mm thick. Although tamoxifen has significant effects on the expression of hormone receptors, the mechanism underlying the development of endometrial polyps does not appear to be mediated by the ER.