Oestrogen receptor and oestrogen regulated proteins in human breast cancer: a review.
Henry JA., Angus B., Horne CH.
Breast growth and development is influenced by oestrogens and the growth of many breast cancers is driven by oestrogens, an effect which is utilised in the endocrine treatment of breast cancer. Oestrogens act by binding to the oestrogen receptor, a specific protein which in turn binds to specific regulatory regions of DNA, thereby altering gene expression. The effects of oestrogens may be mediated by growth factors and other substances under oestrogen regulation. Oestrogen receptor status in breast tumours can be determined by cytosolic radioligand binding assays, enzyme linked immunoassay, immunohistochemistry and measurement of messenger RNA levels. Tumour oestrogen receptor content is an established but not absolute predictor of both response to endocrine therapy and prognosis in breast cancer. Paradoxically, a small proportion of apparently oestrogen receptor negative tumours do respond to endocrine therapy, perhaps reflecting expression of low and unmeasurable levels of receptor or tumour heterogeneity with respect to receptor expression. A larger proportion of oestrogen receptor positive tumours unexpectedly fail to respond to endocrine therapy; in these cases it is possible that oestrogen receptor has become dissociated from the transcriptional and translational events which it normally regulates. Determination of levels of expression of substances regulated by oestrogens can provide information regarding the functional integrity of the oestrogen response pathway and such substances include the progesterone receptor, plasminogen activator, cathepsin D and a variety of messenger RNA sequences.