ABSTRACT
Despite decades of accumulated observational evidence, the role of exogenous hormones on breast cancer has remained unclear. This prospective double-blind randomized trial of 16 608 postmenopausal women with an intact uterus, recruited in 40 US centres between 1993 and 1998, tested experimentally the attributable role of combined equine oestrogen and medroxyprogesterone acetate when compared with placebo. The plan was to follow these women for 8.5 years, but after an average of 5.2 years the trial was stopped when a predetermined index of risks and benefits was exceeded, with the balance indicating that risks exceed benefits. This was a large measure due to the excess cases of invasive breast cancer, which had accumulated 290 new cases. After 4 years of follow-up data, the accumulation of breast cancer cases separated between active hormone replacement therapy (HRT) and placebo, until after 7 years with 166 cases in the active arm compared with 124 in the placebo arm. The balance between the two groups indicates a hazard ratio of 1.26 (1.00-1.59) against exogenous hormones.
