Future possibilities in the prevention of breast cancer: Breast cancer prevention trials

Following the observation that tamoxifen reduced the incidence of contralateral breast cancer when used in the adjuvant setting, it was suggested that prevention of breast cancer in high-risk women might also be possible with this drug [1*,2*]. A pilot study was initiated under the auspices of the United Kingdom Coordinating Committee for Cancer Research at the Royal Marsden Hospital (RMH). As a result of the favourable compliance data and lack of unexpected toxicities in the RMH trial, the United Kingdom Coordinating Committee for Cancer Research launched its main trial, the International Breast Cancer Intervention Study (IBIS) in 1992. Subjects were first enrolled in Australia, because the UK Medical Research Council were concerned about hepatic toxicity of tamoxifen in some strains of rats and their concerns delayed the onset of the study in the UK until November 1993. A similar trial was initiated in the USA in 1992 under the auspices of the National Surgical Adjuvant Breast Project (NSABP) [3*]. All trials were placebo-controlled studies of 5 years of tamoxifen administration.Three studies have reported early results on breast cancer reduction. In the largest study, the NSABP Prevention 1 trial [3*], an almost 50% reduction in new tumours was found. This result is very similar to that which was expected from the adjuvant studies [4*], and led to the early stopping, unblinding and curtailment of the American trial. However, the preliminary results of the RMH trial [5*] and the Italian trial [6*] did not indicate any reduction in breast cancer incidence. These trials remain blinded at the individual level and further follow up is continuing.The present review examines the differences between these trials, and assesses factors that might explain the differences in results. The IBIS trial is not scheduled to complete recruitment until the end of 2000, and results on the reduction of breast cancer incidence are not available. However, some demographic data are avail