Tamoxifen: An Enduring Star
Abstract
In this issue of the Journal, two placebo-controlled studies ( 1 , 2 ) provide long-term results from trials of tamoxifen for the primary prevention of breast cancer in high-risk women. Cuzick et al. ( 1 ) expand on the first International Breast Cancer Intervention Study (IBIS-I), showing after a median follow-up of 8 years and 337 breast cancer events that tamoxifen statistically significantly reduces breast cancer by 29% with no attenuation of benefit after completion of the 5-year treatment schedule. Importantly, their data reveal a greater benefit from tamoxifen on estrogen receptor (ER)–positive disease in the follow-up period and an appreciable tapering of adverse events after the active treatment period, such that the risk–benefit ratio improved with longer follow-up. Similarly, Powles et al. ( 2 ) update the pioneering Royal Marsden trial after a median follow-up of 13 years and 186 events, reporting a non–statistically significant 22% reduction of breast cancer with tamoxifen but a statistically significant 39% reduction of ER-positive disease. The reduction in ER-positive disease was not readily apparent during the 8-year treatment period but became statistically significant with longer follow-up. Tamoxifen had no effect on ER-negative breast cancer in either trial. Notably, in both trials, the incidence of (early-stage) endometrial cancers and the development of venous thromboembolic events were only slightly increased during the entire time spans of both…
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