A double-blind placebo-controlled study to evaluate endometrial safety and gynaecological symptoms in women treated for up to 5 years with tamoxifen or placebo - A substudy for IBIS I Breast Cancer Prevention Trial

Aims of the study: This prospective study was performed to investigate the effects of 5-year's use of tamoxifen in preventive setting on endometrium and gynaecological symptoms. Material and methods: Altogether 96 women were treated either with tamoxifen (TAM, n = 45) or placebo (PLA, n = 51) for up to 5 years in a randomised, double-blind IBIS I breast cancer prevention trial, clinically followed-up for an additional year and for the occurrence of malignancies at least 9 years between 2/1995 and 7/2009 in Finland. The gynaecological follow-up with trans-vaginal ultrasound and endometrial biopsies were performed at baseline, at 2.5 and 5 years and at the 6 years follow-up visit. Results: Women in the TAM group discontinued the treatment significantly more often (44% versus 22%; p = 0.017) and earlier (at 15 versus 30 months; p = 0.044), than those in the PLA group. In postmenopausal women the median endometrial thickness was significantly increased at five years in the TAM group (median 4.3 versus 2.0 mm, p = 0.011), but there was no difference between the groups at one year after the treatment. There were also statistically significantly more referrals to hospitals due to gynaecological findings in the TAM group (risk rates (RR) 3.15; 95% confidence intervals (CI) 1.12-10.10), but no differences in hysterectomy rates or other serious adverse event rates were observed. Conclusions: The discontinuation rate in the TAM group was high, and the discontinuations also occurred early. Even though there were significantly more non-serious gynaecological events during the TAM treatment, routine gynaecological follow-up cannot be recommended. (C) 2012 Elsevier Ltd. All rights reserved.