Development of uterine sarcoma after tamoxifen treatment for breast cancer: report of four cases

Abstract

Tamoxifen (TAM) is widely used in the treatment of breast cancer, and its paradoxical effects on female genital system are well known. During the past 10 years, many descriptions of nonepithelial uterine malignancies related to long-term TAM usage have been reported in the literature. Four uterine sarcoma patients who had history of TAM usage for previous breast cancer are presented in this study. The mean time of exposure to TAM was 6 (range 3-11) years, and the mean cumulative dose of drug was 43.82 g. All patients were postmenopausal, and the mean age was 66 (range 61-73) years at the time of the diagnosis of the uterine malignancy. Two (50%) patients had uterine malignant mixed müllerian tumor, and two (50%) had leiomyosarcoma. In one (25%) patient was diagnosed with endometrial biopsy made for a postmenopausal vaginal bleeding; the others (75%) were asymptomatic and their diseases were diagnosed during the pelvic examination and transvaginal ultrasonography. All patients underwent surgery +/- adjuvant therapy (chemotherapy and/or radiation therapy), and two (50%) patients died because of the sarcoma. In consequence, early detection of TAM-related uterine sarcoma is required for orderly gynecological examination in patients having history of TAM usage for previous breast cancer.

Co-expression of GPR30 and ERβ and their association with disease progression in uterine carcinosarcoma

“…Although these tumors are relatively uncommon, accounting for only 4–9% of all uterine cancers, they are associated with disproportionately higher mortality rates compared with other corpus malignancies 2. While the etiopathogenesis of carcinosarcomas remains poorly understood, these tumors share epidemiologic risk factors with endometrioid-type endometrial carcinomas, including obesity and exposure to selective estrogen receptor modulators (SERMs) 3–5. These observations support a potential role of dysregulated estrogen signaling in the development of this tumor.…”

Surveillance for Endometrial Cancer in Women on Tamoxifen: The Role of Liquid-Based Endometrial Cytology – Cytohistological Correlation in a Population of 168 Women

“…Consistent with this observation, many of the tamoxifen-associated endometrial malignancies are serous papillary or clear cell carcinomas [6][7][8][9] . Some tamoxifen-related uterine sarcomas have also been described [10] .…”

Tumeur müllérienne mixte de l’utérus après traitement par tamoxifène pour cancer du sein : à propos d’un cas

“…En effet, il a été démontré que le traitement par tamoxifène pendant cinq ans, après traitement du cancer du sein, réduisait le risque de récidive annuelle du cancer et sa mortalité, respectivement de 41 et 34 % [9]. Toutefois, les données de la littérature ont démontré des effets paradoxaux antiestrogéni-ques et agonistes des estrogènes sur le tractus génital féminin [4][5][6][7] entraînant l'apparition de polypes de l'endomètre, d'hyperplasie et de cancers de l'endomètre. Il n'y a pas d'argument fort pour établir un lien entre le traitement par tamoxifène et l'apparition d'un carcinosarcome utérin, car le mécanisme de l'effet oncogène du tamoxifène n'est pas encore clairement établi [10].…”

“…La TMM survient le plus souvent chez des femmes ménopausées, avec une moyenne d'âge de 65 ans. Cette pathologie développée à partir de l'endomètre concerne le plus souvent des femmes venant consulter pour des métrorragies postménopausiques [4][5][6]. Le pronostic est souvent médiocre, avec un taux de survie à cinq ans estimé entre 15 et 50 %.…”