984 Chemoprevention of breast cancer with tamoxifen

Abstract

A pilot randomized placebo-controlled trial was started at the Royal Marsden Hospital in 1986 using tamoxifen in healthy women at increased risk of developing breast cancer. Nearly 2400 women with a strong family history of breast cancer have since been accrued into this pilot programme. Participants have been randomly allocated to receive either tamoxifen 20 mgs/day or placebo for up to 8 years. Compliance at 5 years is maintained at approximately 80% for women on placebo, compared to 70% for those on tamoxifen. Acute symptomatic toxicity is low and primarily relates to hot flushes, vaginal discharge and menstrual irregularities. Monitoring of cholesterol and clotting factors showed no adverse effects. The results of bone mineral density as measured by dual energy x-ray absorption are currently being evaluated. Gynaecological assessment using transvaginal ultrasonography has been carried out in this programme. We have identified a significant increase in the incidence of ovarian cysts, uterine fibroids enlarged uterus, endometrial thickening (ET), endometrial polyps and histological evidence of atypical hyperplasia (AH) in patients on tamoxifen. Histological evidence of AH occurred only in women with ET > 8 mms on transvaginal ultrasound, thereby identifying a subgroup for further assessment including hysteroscopy, endometrial biopsy and removal of endometrial polyps. Success of this pilot programme has encouraged the commencement of National trials in the U.S.A., UK. and Italy aimed at evaluating tamoxifen as a breast cancer chemopreventative agent. A pilot randomized placebo-controlled trial was started at the Royal Marsden Hospital in 1986 using tamoxifen in healthy women at increased risk of developing breast cancer. Nearly 2400 women with a strong family history of breast cancer have since been accrued into this pilot programme. Participants have been randomly allocated to receive either tamoxifen 20 mgs/day or placebo for up to 8 years. Compliance at 5 years is maintained at approximately 80% for women on placebo, compared to 70% for those on tamoxifen. Acute symptomatic toxicity is low and primarily relates to hot flushes, vaginal discharge and menstrual irregularities. Monitoring of cholesterol and clotting factors showed no adverse effects. The results of bone mineral density as measured by dual energy x-ray absorption are currently being evaluated. Gynaecological assessment using transvaginal ultrasonography has been carried out in this programme. We have identified a significant increase in the incidence of ovarian cysts, uterine fibroids enlarged uterus, endometrial thickening (ET), endometrial polyps and histological evidence of atypical hyperplasia (AH) in patients on tamoxifen. Histological evidence of AH occurred only in women with ET > 8 mms on transvaginal ultrasound, thereby identifying a subgroup for further assessment including hysteroscopy, endometrial biopsy and removal of endometrial polyps. Success of this pilot programme has encouraged the commencement of National trials in the U.S.A., UK. and Italy aimed at evaluating tamoxifen as a breast cancer chemopreventative agent.