THE ROYAL-MARSDEN-HOSPITAL PILOT TAMOXIFEN CHEMOPREVENTION TRIAL

A pilot randomised placebo controlled trial using tamoxifen in healthy women at increased risk of developing breast cancer, has been underta ken in order to evaluate the problems of accrual, acute symptomatic to xicity, compliance, and safety as a basis for subsequent large nationa l multicentre trials designed to test whether tamoxifen can chemopreve nt breast cancer. From October 1986 until June 1993, 2012 healthy wome n with an increased risk of developing breast cancer, usually because of a strong family history, were randomly allocated to receive tamoxif en 20 mgs/day or placebo for up to 8 years if possible. Accrual remain ed high in spite of extensive informed consent regarding potential ris k. Acute symptomatic toxicity was low for participants on tamoxifen or placebo and compliance remained correspondingly high with a predicted 77% of women on tamoxifen and 82% of women on placebo continuing medi cation at 5 years. There was a significant increase in hot flushes (34 % versus 20%) mostly in premenopausal women (p < 0.005), vaginal disch arge (16% versus 4%, p < 0.005), and menstrual irregularities (14% ver sus 9%, p < 0.005). The requirements for hormone replacement therapy f or women on tamoxifen or placebo were the same. Safety monitoring indi cates no adverse anti oestrogenic effects of tamoxifen. There was no o bvious effect of tamoxifen on bone mineral densities (single photon ra dial absorption). The fibrinogen and antithrombin III were both lowere d, resulting in no observed detrimental effect on the ratio of these c lotting factors. There was a significant reduction in the serum choles terol maintained out to 5 years. Annual pelvic assessment using transv aginal ultrasound indicates an increased incidence of uterine fibromat a and benign ovarian cysts. These results have encouraged the commence ment of the NSABP national trial in the USA, and the subsequent start of national trials in Italy and the UK, which together should provide sufficient evidence to evaluate the efficacy of tamoxifen for preventi on of breast cancer.