Overdiagnosis in Breast Cancer Chemoprevention Trials

Several randomized controlled trials have demonstrated that the preventive use of an antiestrogen agent such as tamoxifen, raloxifene, anastrozole, or exemestane will reduce the incidence of estrogen receptor (er)–positive breast cancers by 50% or more. The reduction in risk becomes apparent shortly after tamoxifen initiation. However, no mortality benefit has yet been demonstrated with tamoxifen or any other agent, an effect that might be statistical: that is, the statistical power to detect a difference in mortality could be lacking because deaths from breast cancer are far fewer in number than cases of breast cancer, and because the average time to cancer is much shorter than the time to death. In other words, it could be too early to see an effect. However, the lack of an observed survival benefit might also be a result of chemoprevention agents preferentially preventing cancers that would rarely lead to death. That paradigm extends the (controversial) concepts of overdiagnosis and of the potential for spontaneous regression of some lowgrade breast cancers [...]