Estrogen/Estrogen Antagonist Regulation of the Cell Cycle in Breast Cancer Cells

Abstract:: The role of estrogen in the growth of breast cancer was recognised over a century ago when it was shown that ovariectomy in premenopausal women with breast cancer resulted in tumor regression (Beatson 1896). Subsequent research showed that estrogen exerted its proliferative effects through a specific receptor (estrogen receptor-ER) and was essential for the initiation and progression of mammary cancer in experimental animals. This and other observations, such as the correlation between ER status of the tumor and a positive response to endocrine therapy, led to the development of estrogen antagonists (antiestrogens) for the treatment of breast cancer (Lerner and Jordan 1990). Tamoxifen, the antiestrogen most commonly employed in the treatment of hormone sensitive breast cancer, significantly decreases the rates of both disease recurrence and death (Early Breast Cancer Trialists’ Collaborative Group 1992; Early Breast Cancer Trialists’ Collaborative Group 1998; Fisher et al. 2001). However, tamoxifen therapy is limited by the frequent development of cellular resistance. In addition, synthetic nonsteroidal antiestrogens like tamoxifen possess both estrogen agonist and antagonist activity and as such have the potential to induce proliferative side effects in other reproductive organs such as the endometrium (MacGregor and Jordan 1998).

Authors:: JS Carroll, OWJ Prall, CM Sergio, EM Rogan, CKW Watts, EA Musgrove, RL Sutherland

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