Clinical evidence for the involvement of oestrogen in the development and progression of breast cancer

Abstract

SynopsisOestrogens may be involved in breast cancer development by at least three mechanisms, all of which involve stimulation of growth. Firstly, they may stimulate proliferation of the normal gland and possibly expand the pool of cells susceptible to carcinogens; secondly, they may expand the population of cells initiated by carcinogens by a promoting action to produce clinically detectable tumours; and thirdly, they may stimulate the growth and progression of infiltrating tumours. All of these effects are probably produced by interactions with the oestrogen receptor. There is suggestive evidence from immunocytochemical studies that promotion to the phase of carcinoma in situ in volves expansion of a receptor-positive clone of cells. After progression, there is a gradual loss of endocrine responsiveness either because of loss of the receptor protein or of receptor function. The high proportion of receptor-positive cells in early malignant lesions holds great hope for preventive strategies using anti-oestrogens for suppression of ovarian oestrogen production.