The Royal Marsden Hospital (RMH) trial: key points and remaining questions.

The reported interim analysis of the Royal Marsden chemoprevention trial, giving tamoxifen (20 mg/day) for up to 8 years to healthy women at increased risk of breast cancer because of a family history, has failed to confirm the 49% reduction in overall early incidence of breast cancer reported from the National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trial. Although statistically compatible, this discrepancy in results raises the possibility that the sensitivity to tamoxifen chemoprevention may depend on the population characteristics of the participants in the two trials. Younger women who do not have lobular carcinoma in situ or atypical ductal hyperplasia, or who may be at high risk of carrying a breast cancer predisposing gene, may be relatively resistant to tamoxifen chemoprevention. Furthermore, the clinical benefit of a reduction in the early incidence of breast cancer by using tamoxifen in healthy women has not been clearly established by the P-1 trial because of the lack of mortality data. Use of tamoxifen for risk reduction in healthy women needs to take into account these factors, and more information needs to be gained from the continuing placebo-controlled trials that are under way.