Current endocrine approaches to breast cancer (BC) prevention are targeted mainly at the estrogen receptor alpha (ERa) (1). Endocrine prevention depends upon either reducing the concentration of estrogen reaching ERa+ breast epithelial cells [estrogen deprivation (ED)] by, for example, ovarian suppression in premenopausal women, or aromatase inhibition in postmenopausal women, or by blocking the interaction of estrogen with ERa by selective estrogen receptor modulators (SERMs) such as tamoxifen (Tarn) and raloxifene (Ral). Observational studies (2-11) and randomised controlled trials (12-25) indicate that treatment by ED and SERMS reduces the risk of subsequent BC by approximately 50% and that this effect is prolonged (16, 18, 20, 26). In the human breast, ERa is detectable in epithelial cells of lobules and ducts and not in the stroma (27). However, it is not clear whether normal, premalignant or malignant epithelial cells are the targets for endocrine prevention. In this chapter, we summarise the results of endocrine prevention trials to date and what is known about the response of the three types of potential target structures to estrogen stimulation and inhibition by ED and SERMS.
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