INTERIM ANALYSIS OF THE INCIDENCE OF BREAST-CANCER IN THE ROYAL-MARSDEN-HOSPITAL TAMOXIFEN RANDOMIZED CHEMOPREVENTION TRIAL

Background Tamoxifen, a drug with antioestrogenic effects, is predicte d to prevent the occurrence of breast cancer, We have undertaken a tri al of tamoxifen in healthy women who are at increased risk of breast c ancer because of family history. We report a planned interim analysis, Methods Between October, 1986, and April, 1996, we accrued 2494 healt hy women aged between 30 and 70 with a family history of breast cancer , They have been randomised (double blind) to receive tamoxifen 20 mg per day orally or placebo for up to 8 years. Follow-up included clinic al assessment, annual mammography, and assessment of toxicity and comp liance. The primary endpoint was the occurrence of breast cancer, whic h was analysed on an intention-to-treat basis with a survival curve. F indings With a median follow-up of 70 months, 2471 women (tamoxifen 12 38, placebo 1233) were suitable for analysis, The groups were evenly m atched at baseline, and compliance was good. The overall frequency of breast cancer is the same for women on tamoxifen or placebo (tamoxifen 34, placebo 36, relative risk 1.06 [95% CI 0.7-1.7], p=0.8). Particip ants who were already on hormone-replacement therapy when they entered the study had an increased risk of breast cancer compared with nonuse rs. Those participants who started such therapy while on trial had a s ignificantly reduced risk. The safety profile of tamoxifen was as expe cted. Interpretation We have been unable to show any effect of tamoxif en on breast-cancer incidence in healthy women, contrary to the report from the NSABP-P1 study showing a 45% reduction in healthy women give n tamoxifen versus placebo. Differences in the study populations for t he two trials may underlie these conflicting findings: eligibility in our trial was based predominantly on a strong family history of breast cancer whereas in the NSABP trial was mostly based on non-genetic ris k factors. The importance of oestrogen promotion may vary between such populations.