title: Results and implications of the Royal Marsden and other tamoxifen chemoprevention trials: an alternative view.
abstract: At the time of the release of the findings of the Breast Cancer Prevention Trial (BCPT), early interim results from two smaller European studies were also released. These smaller studies included one from the Royal Marsden (RM) Hospital in London, England, and another from the Italian National Cancer Institute. Since then, there has been much discussion about the relevance of the interim findings from the European studies and the likely reason for the failure of these studies to find a treatment effect. In some instances, the discussion has been incomplete or inconsistent with the observations from the trial. This has caused some confusion regarding the likely differences among the three studies of breast cancer prevention with tamoxifen. Recently, investigators from the RM study have published their interpretation of the reasons for the negative findings from the European studies. The discussions of the RM investigators are reviewed and used as a basis to illustrate some misconceptions regarding key differences in trial design and implementation among the BCPT and the European trials. The investigator discussions are also used to illustrate the significance of performing an appropriate benefit/risk assessment to identify women who would likely have a net beneficial effect when using tamoxifen to reduce the risk of breast cancer occurrence. Differences in terms of the characteristics of the study populations resulting in inadequate statistical power is the most likely reason for the failure to detect treatment differences in the European trials. Possible confounding due to the use of hormone replacement therapy is another reason that must be considered. Also, benefit/risk analysis indicates that tamoxifen has substantial public health potential as an approach to reduce breast cancer incidence and the physical and mental morbidity associated with this disease. The drug cannot be used indiscriminately due to the potential side effects, but benefit/risk assessment methodology can be used to identify substantial numbers of women in whom treatment would provide a net beneficial effect.
authors.affiliation: University of Pittsburgh, Graduate School of Public Health, 130 DeSoto Street, Room 316 Parran Hall, Pittsburgh, PA 15261, USA. costan@nsabp.pitt.edu
authors.forename: J P
authors.initials: JP
authors.lastname: Costantino
authors.forename: V G
authors.initials: VG
authors.lastname: Vogel
mesh_terms: D001943:Breast Neoplasms / Q000517:prevention & control*; D018890:Chemoprevention; D002986:Clinical Trials as Topic; D004739:England; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D007558:Italy; D012306:Risk; D018570:Risk Assessment; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D004965:Estrogen Antagonists; D013629:Tamoxifen