Cellular homeostasis and the breast

Increasing our knowledge regarding the control of cellular homeostasis in the normal human breast is important in understanding how breast tumours arise and whether compounds used for hormone replacement therapy are able to promote tumour formation In our studies on tissue from pre-menopausal, non-pregnant, non-lactating women, oestradiol is the main ovarian steroid mitogen for the breast epithelium whereas progesterone has little or no effect. Oestradiol appears to influence proliferative activity indirectly via oestrogen-receptor positive cells which control the activity of adjacent division competent cells by means of paracrine or juxtacrine growth factors. After the menopause, however, a mitogenic effect of progesterone becomes apparent which may be due to the reduction in endogenous oestradiol levels or, possibly, to tissue specific alterations in steroid sensitivity. Whatever the mechanism, the proliferative effects of progesterone on the post-menopausal breast have implications for the use of HRT.