To the Editor The Viewpoint by Narod1 creates a moment of pause concerning current views of chemoprevention, using any agents in high-risk populations of women. The successful use of tamoxifen citrate for the adjuvant treatment of breast cancer has saved perhaps millions of lives and continues to do so. Tamoxifen in the title is a convenient hook. The chemoprevention strategy, by identifying populations, was destined to die eventually because few individuals benefit but nearly everyone experiences adverse effects or worries about them. In 1990 tamoxifen was the only drug to move forward into chemoprevention trials using large, correctly powered populations but only at risk for breast cancer and very low incidence. The translational research that identified the small risk of endometrial cancer with tamoxifen use2 served to protect women from a serious adverse effect. However, this created a justifiable concern for women without disease. Additionally, the description of rat liver carcinogenesis with tamoxifen2,3 in 1992 was not reassuring to women. Despite the fact that the US Food and Drug Administration approved tamoxifen for risk reduction in 1998, few women chose this option because of adverse effects. Furthermore, adherence dwindles in the treatment setting, when there is certainty of death on recurrence. Adherence is an issue in chemoprevention. Nevertheless, progress has been made that should not be discounted. In 1990, before the initiation of chemoprevention trials, an alternate strategy using selective estrogen receptor modulators (SERMs) was stated: “Important clues have been garnered about the effects of tamoxifen on bones and lipids so it is possible that derivatives could find targeted applications to retard osteoporosis or atherosclerosis… [These] may significantly retard the development of breast cancer. The targeted population would be postmenopausal women in general, thereby avoiding the requirement to select a high-risk group to prevent breast cancer.”4(p5684) The result was raloxifene hydrochloride, which reduces the incidence of breast cancer during the treatment and prevention of osteoporosis but without the worry of endometrial and rat liver cancer.5 Better SERMs are on the way to target multiple diseases. Specifically, the extended use of SERMs to treat and prevent osteoporosis and, perhaps, coronary heart disease makes this strategy of value to prevent the morbidity following the diagnosis of tens of thousands of breast cancers. This is a bonus to medicine and health care management.4 The failure of past chemoprevention clinical strategies, focusing on populations rather than delivering precision medicine, can no longer be justified.
Jordan VC. Differing Perspectives on Breast Cancer Chemoprevention. JAMA Oncol. 2016;2(2):276. doi:10.1001/jamaoncol.2015.3906