Tamoxifen treatment for breast cancer and risk of endometrial cancer: a case-control study.

BACKGROUND: Tamoxifen treatment of breast cancer is associated with an increased risk of endometrial cancer, but tamoxifen-related risks of endometrial cancer are unclear in premenopausal women, in long-term users of tamoxifen, and in women for whom several years have passed since ending treatment. We conducted a case-control study in Britain to investigate these risks. METHODS: We compared treatment information on 813 case patients who had endometrial cancer after their diagnosis for breast cancer and 1067 control patients who had breast cancer but not subsequent endometrial cancer. We assessed risk by conditional logistic regression analysis. All statistical tests were two-sided. RESULTS: Overall, tamoxifen treatment, compared with no treatment, was associated with an increased risk of endometrial cancer (odds ratio [OR] = 2.4; 95% confidence interval [CI] = 1.8 to 3.0). Risk increased statistically significantly (P(trend)<.001) with duration of treatment (for > or =5 years of treatment compared with no treatment, OR = 3.6, 95% CI = 2.6 to 4.8). As an indication of background levels of treatment, 16% of control patients received 5 years or more of treatment. Risk of endometrial cancer adjusted for treatment duration did not diminish in follow-up to at least 5 years after the last treatment ended. Risk of endometrial cancer was not associated with the daily dose of tamoxifen and was comparable in pre- and postmenopausal women. Ever treatment with tamoxifen was associated with a much greater risk of Mullerian and mesodermal mixed endometrial tumors (OR = 13.5, 95% CI = 4.1 to 44.5) than of adenocarcinoma (OR = 2.1, 95% CI = 1.6 to 2.7) or clear cell and papillary serous tumors (OR = 3.1, 95% CI = 0.8 to 17.9). CONCLUSIONS: There is an increasing risk of endometrial cancer associated with longer tamoxifen treatment, extending well beyond 5 years. The increased risk of endometrial cancer associated with tamoxifen treatment should be considered clinically for both premenopausal and postmenopausal women during treatment and for at least 5 years after the last treatment.

Malignant mixed mesodermal tumor after tamoxifen therapy for breast cancer.

BACKGROUND: The risk of tamoxifen related endometrial neoplasm has been confirmed by multiple studies. Especially rare endometrial tumors seem to develop more frequently under tamoxifen therapy. A recent analysis showed a substantially higher risk for malignant mixed mesodermal tumor (MMMT; designated in the WHO classification of female genital tract neoplasms as carcinosarcoma) in association with tamoxifen intake. CASE: We are reporting a case of a 40-year-old multiparous premenopausal woman who received tamoxifen 20 mg daily for 2 years after the surgical treatment of breast cancer and subsequent adjuvant chemotherapy. Two years after initiation of tamoxifen treatment, the patient developed an MMMT of the uterus. More than 64 months after radical hysterectomy, salpingo-oophorectomy, and pelvic lymphadenectomy, she remains recurrence-free for MMMT. Unfortunately, she developed a local recurrence of her breast cancer in 2003. After surgical treatment, she is currently being treated with anastrozole. CONCLUSION: We are reporting a rare case of a premenopausal patient who developed a MMMT within short time of tamoxifen exposure for stage I breast cancer.

Endometrial mesodermal mixed tumor occurring after tamoxifen treatment: report on a new case and review of the literature.

BACKGROUND: Anti oestrogenic treatment is widely used for breast cancer treatment and prevention of recurrence. Because of concomitant estrogenic effects, tamoxifen exerts carcinogenic properties on the endometrium. Although secondary endometrial cancers usually present as pure adenocarcinomas, other types of rare tumors have also been reported. PATIENTS AND METHODS: Herein we describe the clinical, pathological as well as therapeutic aspects of a new case of endometrial mesodermal mixed tumor occurring after long-term tamoxifen therapy. RESULTS: The present case occured five years after cessation of a five years tamoxifen treatment. The patient failed to respond to doxorubicin and cyclophosphamide when combined to 5-fluorouracil (5-FU), but she reached complete response when the same two drugs were used with carboplatin, suggesting the potential usefullness of platinum derivatives. CONCLUSIONS: A longer latency period might be observed for endometrial mesodermal mixed tumors as compared to adenocarcinomas and could justify a prolonged clinical and ultrasonographic follow-up of patients during and after tamoxifen treatment. When indicated, chemotherapy might require the use of platinum derivatives in this particular type of secondary tumor.

Hormone replacement therapy and risk of epithelial ovarian cancer.

It has been suggested that oestrogen replacement therapy is associated with risk of epithelial ovarian cancer of the endometrioid type. Using data from an Australian population-based case-control study, the relation between unopposed oestrogen replacement therapy and epithelial ovarian cancer, both overall and according to histological type, was examined. A total of 793 eligible incident cases of epithelial ovarian cancer diagnosed from 1990 to 1993 among women living in Queensland, New South Wales and Victoria were identified. These were compared with 855 eligible female controls selected at random from the electoral roll, stratified by age and geographic region. Trained interviewers administered standard questionnaires to obtain detailed reproductive and contraceptive histories, as well as details about hormone replacement therapy and pelvic operations. No clear associations were observed between use of hormone replacement therapy overall and risk of ovarian cancer. Unopposed oestrogen replacement therapy was, however, associated with a significant increase in risk of endometrioid or clear cell epithelial ovarian tumours (odds ratio (OR) 2.56; 95% confidence interval (CI) 1.32-4.94). In addition, the risk associated with oestrogen replacement therapy was much larger in women with an intact genital tract (OR 3.00; 95% CI 1.54-5.85) than in those with a history of either hysterectomy or tubal ligation. Post-menopausal oestrogen replacement therapy may, therefore, be a risk factor associated with endometrioid and clear cell tumours in particular. Additionally, the risk may be increased predominantly in women with an intact genital tract. These associations could reflect a possible role of endometriosis in the development of endometrioid or clear cell ovarian tumours.