To the Editor Despite its continued ability to prevent a substantial proportion of breast cancer cases for at least 15 years after cessation of treatment, Narod1 argues that breast cancer prevention with tamoxifen is dead. We dispute this contention. While aromatase inhibitors show evidence of greater effectiveness, they are only for postmenopausal women, and an important time to offer preventive therapy is during the late premenopausal period, in which tamoxifen is the only proven agent. There have now been 4 large tamoxifen prevention trials, and the clear evidence for substantial reductions in breast cancer incidence has been summarized in Cuzick et al.2 However, despite the long follow-up in 2 of them, it is still too early to evaluate its effect on breast cancer mortality. This was not the primary end point for any of these trials and breast cancer incidence still exceeds mortality by more than 10-fold, so the number of events needed to see a mortality effect is still inadequate. For example, in IBIS-I, after a 16-year median follow-up, there have been 503 invasive breast cancers but only 57 breast cancer deaths. As cancer occurred at a constant rate in IBIS-I, median follow-up after cancer is only 8 years, which again is inadequate to evaluate mortality. Women entered this trial at a median age of 49.9 years and more than 95% (6806 of 7154) were still alive at the last report, so they still have much life to be lived. We are in the process of analyzing metastatic spread in cases, which will give an earlier indication of the likely effect on mortality, but even this will take more time. In addition, because tamoxifen therapy only prevents the less fatal estrogen receptor–positive breast cancer, an 18% mortality reduction is projected.3 To demonstrate a mortality reduction with even 50% power, 216 breast cancer deaths would be needed and to date only 92 have been reported in all of these trials.2,4
Cuzick J, Wickerham L, Powles T. Differing Perspectives on Breast Cancer Chemoprevention. JAMA Oncol. 2016;2(2):276–277. doi:10.1001/jamaoncol.2015.4406
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