Risk of endometrial cancer in breast cancer patients under long-term adjuvant treatment with tamoxifen

Aims: To evaluate the relative risk of endometrial cancer with respect to the expected underlying incidence in breast cancer patients undergoing long-term adjuvant tamoxifen therapy. Methods: A total of 1010 postmenopausal breast cancer patients receiving adjuvant tamoxifen and with a first negative endometrial ultrasonography (cutoff for abnormal endometrial thickness >5 mm) were followed by annual transvaginal ultrasonography. Abnormal endometrial thickness prompted an outpatient endometrial biopsy or curettage under anesthesia in the case of cervical stenosis and increasing endometrial thickness. The standardized incidence ratio (SIR) with respect to underlying incidence was determined. Results: A total of 1,010 eligible subjects who had been receiving tamoxifen for an average of 51 months were enrolled and followed for a total of 2,361 patient-years between January 1993 and Decem ber 1996. Five cases of endometrial cancer were observed in the study period: 1 was detected at screening, and 4 were diagnosed for vaginal bleeding in the interval between screen-examinations. SIR was 4.0 (95% confidence interval, 1.3-9.4) and increased to 4.8 (CI, 1.6-10.5) when the single cancer detected at first screening was considered as incident. Conclusions: This study adds evidence to the hypothesis that longterm tamoxifen treatment may be responsible for a relevant increase in the risk of developing endometrial cancer. Surveillance based on endometrial ultrasonography was poorly sensitive, but the favorable stage at diagnosis of screen-detected or interval endometrial cancers does not support a more aggressive screening approach.