ABSTRACT
I. INTRODUCTION Breast cancer is a classic hormone-dependent malignancy. The association between estrogen and carcinoma of the breast was recognized over 100 years ago in a report by Beatson, which showed that patients with inoperable breast tumors frequently respond to surgical oophorectomy (Beatson, 1896). Since then, a substantial body of experimental, clinical, and epidemiological evidence has indicated that steroid hormones, namely estrogens and progestins, play a major role in both the etiology and progression of breast cancer. In fact, the known risk factors for breast cancer largely reflect the extent of lifetime exposure of the breast to these two hormones (Thomas et al., 1997). The presence of an intracellular estrogen-binding protein, initially called estrophilin, in estrogen target organs of animals and also in human breast cancers was reported through the 1960s, after radiolabeled estrogens became available for research (Jensen and Jacobson, 1962). The importance of estrogen in the development and promotion of growth of both normal and neoplastic breast led to a massive research effort into the mechanisms whereby estrogen exerts its effects, with the eventual elucidation (Toft and Gorski, 1966) and cloning of the first estrogen receptor (ER), now called ERα (Green et al., 1986a,b). Another level of intricacy to this research field was introduced only recently with the discovery of a second ER, called ERβ.
