Breast cancer, stem cells and sex hormones. Part 3: The impact of the menopause and hormone replacement

Breast stem cells are long-lived cells and so are exposed to carcinogenic influences for much longer than normal differentiated breast ductal cells. It is hypothesized that these stem cells are the major site of carcinogenesis within the breast. Epidemiological studies have suggested that early life events and early first pregnancy profoundly affect breast cancer risk in adult life. It seems likely that these observations may be, at least partially explained, through changes in stem cell number and function. After menopause, despite very low systemic oestradiol levels, intra-breast oestradiol concentrations remain high due to increased biosynthesis of oestrogens in breast fat and stromal tissue. Stem cells are usually tightly regulated within a niche. The malignant process seems to involve changes in not only the cancer stem cell but also its microenvironment. The likely impact of hormone replacement and SERMs on stem cell function is discussed.