THE LOSS OF ESTROGEN AND PROGESTERONE-RECEPTOR GENE-EXPRESSION IN HUMAN BREAST-CANCER

Hormone responsiveness is a critical determinant of breast cancer prog ression and management, and the response to endocrine therapy is highl y correlated with the estrogen receptor (ER)(3) and progesterone recep tor (PR) status of tumor cells. Thus, key areas of study in breast can cer are those mechanisms that regulate ER and PR expression in normal and malignant breast tissues. One-third of all breast cancers lack ER and PR; these conditions are associated with less differentiated tumor s and poorer clinical outcome. In addition, approximately one-half of PR-positive tumors lack PR protein and patients with this phenotype ar e less likely to respond to hormonal therapies than those whose tumors express both receptors. Since PR is induced by ER; its presence is a marker of a functional ER. In this review, we will discuss possible me chanisms for loss of ER and PR gene expression, especially structural changes within each gene including deletions, polymorphisms or methyla tion. Improved understanding of the pathways that lead to loss of ER a nd/or PR proteins should allow the development of better predictive in dicators as well as novel therapeutic approaches to target these hormo ne-independent cancers.