타목시펜 치료를 받는 유방암 환자에서 자궁내막의 병리
Endometrial pathologies in tamoxifen-treated breast cancer patients
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목적: 유방암 환자에서 수술 후 재발 및 전이 방지를 위해 사용되고 있는 타목시펜이 자궁내막에 미치는 영향을 알아보기 위하 여 연구를 시행하였다. 방법: 유방암 수술 후 타목시펜 치료를 받는 폐경된 유방암 환자 664명 중 부인과에 진료 의뢰된 55명을 대상으로 부인과적 진찰, 자궁내막초음파검사, 자궁내막조직검사 및 면역조직화학 염색을 시행하였다. 결과: 타목시펜 치료를 받은 유방암 환자에서 자궁내막의 양성 병리소견 중 가장 많은 조직학적 유형은 자궁내막 용종이었다. 초음파로 측정한 자궁내막의 두께가 10 mm을 초과할 때 자궁내막 용종과 자궁내막암이 유의하게 증가하였다. 타목시펜으로 치료받은 환자에서 발생한 자궁내막 용종과 대조군을 ER, PR, Ki-67에 대한 면역조직화학염색의 시행 결과 ER의 염색점수 는 타목시펜을 복용한 군의 용종의 선에서 낮은 값을 보이고 기질에서의 PR값은 높았으며 Ki-67은 높은 점수를 보였다. 결론: 타목시펜으로 치료받은 유방암 환자는 정기적인 부인과 검진이 필요할 것으로 보인다. 또한 투여기간이 길어질수록, 초 음파 검사상 자궁내막의 두께가 10 mm가 넘을 경우, 그리고 환자가 질출혈의 증상이 있는 경우는 자궁내막암을 포함한 자궁내막의 병변의 발생 가능성이 있으므로 반드시 자궁내막의 병리에 대한 검사를 시행하여야 할 것이다. 또한 타목시펜을 복용한 환자에서 자궁내막 용종의 발생이 많은 것은 타목시펜이 용종의 호르몬 수용체 및 세포증식에 영향을 미치기 때문이 라고 보인다.
Abstract
Objective: Tamoxifen is a nonsteroidal hormone that functions as a selective estrogen-receptor (ER) modulator in breast tissue. It is the firstchoice 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.
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