Molecular basis of steroid hormone action in breast cancer and its clinical implications

The measurement of steroid hormone receptors in tumors from patients with breast cancer is now well established. Data have accumulated that seem to indicate that breast cancer patients may be selected for endocrine or adjuvant therapy on the basis of the presence or absence of estrogen receptors. Furthermore, patients without detectable estrogen receptors seem to have a greater likelihood of early recurrence following mastectomy. We describe recent findings on the mechanism of action of both estrogens and antiestrogens at the normal target cell level. Evidence for a similar mechanism of action for estrogens and antiestrogens in the hormone-responsive mammary tumor cell is presented on the basis of studies in hormone-dependent, dimethylbenz(a)anthracene-induced mammary carcinoma in the rat, and the cell line MCF-7 derived from a human breast carcinoma. The interaction of estrogens and antiestrogens with their receptors in the cytoplasms and nucleus in solid human breast tumors is discussed and analyzed in terms of the potential clinical application to breast cancer management.