Response: Re: Risk/Benefit Assessment of Tamoxifen to Prevent Breast Cancer—Still a Work in Progress?

Extract

We recognize the importance of the work by Gail et al. (1) in beginning to assess the risk to benefit ratio for tamoxifen as a preventive strategy for women at higher risk for breast cancer, and we do not disagree with the conceptual model used by Gail et al. as it applies to the population studied. Thus, for white women, this model may provide important guidelines for breast cancer prevention. We did not criticize the use of the Breast Cancer Prevention Trial (BCPT) and general population databases to estimate tamoxifen's risk in the general population. Our concern was that, because of the unforgivably small number of minority women in the BCPT, these data are definitive for white women but are not definitive for minority women. Therefore, regardless of the sophistication of the analytic methodology, the guidelines for providing or withholding tamoxifen preventive therapy in minority women simply are not supported by data from an inadequate sample size of minority women. In their letter, Gail et al. state “if one is willing to infer from the BCPT data, derived principally from white women, that tamoxifen lowers . . . it seems reasonable to assume that tamoxifen's effects on other health outcomes. . . .” What is “reasonable to assume” as opposed to what is supported by data has, throughout the history of medicine, been all too often distressingly divergent. There are multiple examples of substantial ethnic differences in drug disposition and responsiveness (2). Thus, we are unwilling to infer that data from more than 13000 white women, but from only 220 African-American women, and 249 women of other ethnicity will necessarily predict the effects of tamoxifen in women of African-American and other ethnicities. Rather than base guidelines for the administration of a powerful drug on inferences, we re-emphasize the need to recruit adequate numbers of minority women in important clinical trials.