Factors of risk for breast cancer influencing post-menopausal long-term hormone replacement therapy

The advantages of hormone replacement therapy (HRT) are well documented in contrasting the symptomatology of climacterium and in reducing morbidity and mortality associated with coronary heart disease and osteoporotic fractures of postmenopausal age. However, growing evidence points to increased breast cancer risk in HRT long-term users, and the adverse effect would, obviously, overwhelm any other benefit. At present, the risk/benefit ratio of HRT is an object of hot debate, and we feel it necessary and urgent to select women who can safely benefit from HRT and women whose risk of breast cancer can be perilously increased by the raised hormonal levels related to HRT. We have reviewed studies on the breast cancer risk in HRT users and data on the interaction between steroid hormones and breast cancer. Reasoning that the outcome of mammary cancer can be increased by hormonal overstimulation of the breast, we have focused on those factors of risk that could be further enhanced by the exogenous hormonal stimulus of HRT, so as to cause a further significant increase in the risk of breast cancer. We conclude that some biologic and clinical markers, namely android obesity, bone density, mammographic density, androgen and estrogen circulating levels, alcohol consumption, benign breast disease, and familiarity, should be carefully considered before prescribing long-term HRT. Our analysis suggests that HRT could increase the risk of breast cancer and useless in preventing coronary heart disease and osteoporotic fractures when administered in women with positivity for one or more of these markers.