Uterine carcinosarcomas in patients receiving tamoxifen. A report of 19 cases

Abstract

Uterine carcinosarcomas are highly aggressive neoplasms with a tendency to early extrauterine spread, high stage at diagnosis, and a poor prognosis. Tamoxifen is widely used as adjuvant therapy in the treatment of breast cancer and is known to cause endometrial proliferative lesions, including adenocarcinoma. In recent years, there have been occasional reports of uterine carcinosarcoma in patients taking tamoxifen. The aim of this study is to describe the clinicopathologic profile in 19 women taking tamoxifen who subsequently developed uterine carcinosarcoma. Nineteen patients were identified from cases of uterine carcinosarcoma diagnosed at three institutions. The case notes were examined and the pathology reviewed. The age at diagnosis of carcinosarcoma ranged from 47 to 91 years (mean 71 years). All patients were postmenopausal and received 20 mg tamoxifen daily; the duration of treatment ranged from 1 to 15 years (mean 7.1 years). The cumulative dose of tamoxifen ranged from 7.3 to 109.5 g. Ten tumors were stage I, one stage II, seven stage III, and one stage IV. Ten of the carcinosarcomas were homologous, and nine contained heterologous elements in the form of rhabdomyoblasts (six cases) or malignant cartilage (three cases). The overall prognosis was extremely poor. Fifteen patients died within 35 months of the diagnosis of carcinosarcoma (mean 12 months). Two patients are alive with very short follow-up periods, and two were lost to follow-up. The reported data support an association between tamoxifen therapy and the development of uterine carcinosarcoma. The risk is likely to be highest in those patients who have been taking tamoxifen for a prolonged period. A majority of tumors in the present study were stage I, and this suggests that uterine carcinosarcomas in patients taking tamoxifen may be diagnosed at an earlier stage than those arising de novo. However, the prognosis was still poor even with low-stage disease. Properly controlled epidemiological studies are necessary to confirm an association between tamoxifen and uterine carcinosarcoma.

A practical approach to the diagnosis of mixed epithelial and mesenchymal tumours of the uterus

“…Associations include prior tamoxifen therapy, unopposed oestrogens and pelvic irradiation (10-to 20-year time interval). 4,5 Patients usually present with vaginal bleeding, but may have symptoms related to a pelvic mass or metastatic disease. Given that carcinosarcomas are, in essence, of epithelial derivation, they are staged as endometrial carcinomas; this is explicitly stated in the 2009 FIGO staging system for endometrial carcinomas.…”

Molecular markers and clinical behavior of uterine carcinosarcomas: focus on the epithelial tumor component

“…The heterologous component is composed of other components such as rhabdomyosarcoma, chondrosarcoma, osteosarcoma and liposarcoma. 4,5 The proportion of the epithelial and mesenchymal component can vary between individual cases.…”

“…Furthermore, longterm use of tamoxifen after breast cancer has been associated with the development of a uterine carcinosarcoma. 4 Stage of disease, myometrial invasion and vascular invasion are important prognostic factors. Owing to a high tendency to early extrauterine spread, advanced disease is usually present at the time of diagnosis.…”

“…Owing to a high tendency to early extrauterine spread, advanced disease is usually present at the time of diagnosis. 4,13 Prognosis is poor: 5-year survival rates have been reported between 30% and 45.8% in early-stage carcinosarcoma (FIGO stage I/ II) and between 0% and 10% in advanced stage carcinosarcoma (FIGO stage III/IV). 11,12 Until recently, uterine carcinosarcomas were considered as a subtype of uterine sarcomas and were treated correspondingly.…”

Ovarian endometriosis as a premalignant condition: epidemiological, histological and molecular evidence

“…3 Numerous studies suggest that oestrogen and also tamoxifen play important roles in the pathogenesis of all the related tumours. [6][7][8] This suggests at least a theoretical risk for an iatrogenic increase in incidence. Tamoxifen is linked to endometriosis progression, endometrial proliferative disorders within endometriosis and endometrioid adenocarcinoma in endometriosis.…”