Antiestrogens and the Cell Cycle

Recognition of the involvement of estrogen in the growth of breast cancer stemmed from observations made a century ago, when it was shown that ovariectomy in cases of pre-menopausal breast cancer could lead to tumor regression (1). Subsequent research in experimental models of carcinogeninduced mammary cancer revealed that estrogen was essential for both the initiation and progression of the disease. These observations, together with the demonstration that some breast tumors had a specific binding protein for estrogen, the estrogen receptor (ER), and that ER status was correlated with response to endocrine therapy, provided the rationale for the introduction of the antiestrogen tamoxifen in the treatment of breast cancer (2).