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We report four cases of mixed müllerian tumors of the endometrium arising in postmenopausal women taking tamoxifen for breast carcinoma. Various histopathologic features were encountered: one müllerian adenosarcoma and three malignant mixed müllerian tumors so called carcinosarcomas (in one case the sarcomatous component was homologous composed of tissues normally found in the uterus, while the others were heterologous because they were containing some elements normally not found in the uterus). Concern has been raised about prolonged tamoxifen treatment and subsequent occurrence of endometrial adenocarcinoma. Then, attention has been drawn through high-risk histologic subtypes including poorly differentiated patterns, uterine sarcomas and such mixed müllerian tumors. There is no consensus regarding internal surveillance of women receiving tamoxifen. The usefulness of pelvic sonography has not been demonstrated.

Introduction: Tamoxifen--a non steroidal triphenylethyl compound--in addition to having antiestrogenic properties may provoke weak estrogenic effects, the well known "paradoxical effects" on the female genital tractus. Concern has been raised about prolonged tamoxifen treatment and subsequent occurrence of endometrial adenocarcinoma; subsequent attention has been drawn through high risk histologic subtypes including poorly differentiated patterns and uterine sarcomas., Exegesis: We report two cases of uterine sarcoma arising in postmenopausal women taking tamoxifen, 20 mg daily during 38 and 42 months, for breast carcinoma: one leiomyosarcoma and one endometrial stromal sarcoma; both cases were asymptomatic and detected by pelvic sonography., Conclusion: Further studies will be required to establish if there is a relationship between long term tamoxifen exposure and highly aggressive types of cancer of the uterine corpus exhibiting adverse histologic features such as uterine sarcomas. There is no consensus regarding uterine surveillance of women receiving tamoxifen. We advocate an annual gynecologic examination plus imaging by means of transvaginal ultrasonography.

Objective: The aim of this study was the evaluation of endometrial histopathologic findings from 700 patients treated with tamoxifen (Tx) for breast cancer from two medical centers (United States and France)., Methods: A retrospective review of data including histologic slides from 134 hysterectomies and 566 endometrial biopsies from Tx-treated patients who presented with abnormal vaginal bleeding and/or abnormal sonograms was performed. Analysis of histologic characteristics included inactive/atrophic and functional endometria, endometrial polyps, hyperplasia and metaplasia, and endometrial cancer. Duration of Tx therapy was recorded when available, and its correlation with endometrial pathology was assessed., Results: The only statistically significant difference between the data from the United States and France was the number of hysterectomies, which was almost double in France (27% vs 13.7%). Nonpathologic endometria made up 61.14% (inactive/atrophic 46%, functional 15.14%). Pathologic changes were found in 39.86% cases, of which polyps were 23.14%, glandular hyperplasia 8%, and metaplasia 3%; endometrial cancer made up 4.71% (33 cases). Nine cancers were well-differentiated endometrioid adenocarcinomas, and 24 were moderately or poorly differentiated, of which 13 had nonendometrioid components (serous, clear cell, MMMT). Fifteen cancers were found in endometrial polyps; 12 were invasive to the myometrium and 4 to blood vessels. The weight of the uteri exceeded 300 g in 15 cases, with 4 exceeding 900 g. The average age of all patients was 60.91 years and of the cancer patients alone it was 69.26 years. The shortest average duration of Tx therapy (2.5 years) was found in patients with inactive/atrophic endometria and the longest (6.8 years) in patients with endometrial cancer. Patients with endometrial polyps and cancer presented more often with abnormal vaginal bleeding than those with inactive/atrophic endometrium., Conclusions: Most Tx-treated patients had no pathologic endometrial changes. Endometrial polyps, hyperplasia, and metaplasia, consistent with an estrogen-agonist effect of Tx, were found in roughly one-third of all patients. The endometrial cancers were often high-grade and invasive tumors. Patients with endometrial pathology were more often symptomatic than patients with inactive/atrophic endometria., (Copyright 2000 Academic Press.)

Tamoxifen, a non-steroid anti-oestrogen derivative of diethylstilboestrol, is the main drug used for hormone therapy for hormone-dependent breast cancer. This ambivalent drug has both antagonist and agonist effects. While tamoxifen blocks tumour growth it can also have an undesirable agonist effect on the genital tract. The uterus is a target organ for this paradoxical action due to proestrogenic stimulation of the endometrium and the myometrium. We observed eleven cases of uterine fibromyoma during treatment with tamoxifen which required hysterectomy due to increased tumour volume. The pathology report on the surgical specimens did not show any evidence of malignancy. Differential diagnosis is based on sarcomatous degeneration of the fibromyoma and presence of intra-myomatous metastases from the breast. Hysterectomy is indicated in menopaused patients with a symptomatic fibromyomatous uterus before starting long-term anti-oestrogen therapy for hormone-dependent breast cancer.

The authors report a case of endometriosis (adenomyosis + endometrioma) which occurred in a female patient aged 69 years, who had undergone the menopause 15 years previously and who had been taking Tamoxifen for 7 years as an adjuvant treatment for cancer of the breast. Tamoxifen, a non-steroidal anti-estrogen derived from diethylstilbestrol, has a variable antagonist/agonist so that estrogenic stimulation of the female genital tract may occur, particularly of the endometrial mucosa. The reactivation of the endometriosic foci which had become quiescent under the impact of the natural menopause, which, by iatrogenic analogy is included in the series of paradoxical uterine effects of tamoxifen.

The authors report 22 cases of metrorrhagia occurring in the course of adjuvant hormonal therapy for breast cancer using tamoxifen. The anti-oestrogenic effect of this drug is associated with a variable agonistic effect that has been observed in organs with steroid receptors, and especially in the uterus. In this series, the cause of the abnormal bleeding is explained in 17 out of the 22 cases (ie, 3 out of 4) as a paradoxical oestrogen-like effect on the mucosa of the uterus. Two cancers of the endometrium were diagnosed.