The well established association of breast cancer risk with several readily recordable reproductive factors, such as parity, age at first full-term pregnancy and age of menopause, makes them attractive candidates for inclusion in any multi-factorial risk algorithm. Over recent years prospective studies of plasma hormone levels in relation to breast cancer occurrence have revealed that higher plasma oestrogen and androgen levels and lower sex hormone binding globulin levels correlate with increased breast cancer risk in post-menopausal women. It is widely accepted that the mechanism underlying this is, at least in part, the mitogenic effect of the oestrogens on oestrogen receptor positive cells of normal, transforming and frankly malignant breast epithelial cells. There is unresolved controversy about whether direct carcinogenic effects of some oestrogen metabolites, which can clearly be demonstrated in model systems, also have a significant impact in women. Although this is largely unimportant in the potential use of plasma hormone levels for risk estimation, it would be a significant factor in selection of chemopreventive strategy, because oestrogen deprivation (for instance, aromatase inhibitors) would be expected to inhibit such an effect whereas oestrogen antagonists (for instance, tamoxifen) would not.
At present, despite its theoretical justification, measurement of plasma hormones has not been incorporated into risk algorithms. This is partly because of the paucity of well proven standardized assays for use in postmenopausal women and the need for application of such assays in very large sample sets. Such studies are needed to determine the interaction and independent significance of the hormone measurements alongside other more easily measured factors such as body mass index (BMI), which is correlated with plasma oestrogen levels in postmenopausal women as well as being a risk factor itself.