Hormone replacement therapy and breast cancer.

The concern that postmenopausal hormone replacement therapy (HRT) may cause cancer of the breast has lead to an enormous volume of research in epidemiology, endocrinology and tumour cell biology. The epidemiology has become extremely sophisticated because the anticipated effect is small and there are several confounding factors. The consensus today is that long-term HRT (>10 years) is associated with an increase in the risk of breast cancer which, on average, is equivalent to delaying menopause for the same period of time that the patient is on treatment. The risk is related to endogenous and exogenous oestrogen levels. Studies that have investigated individual susceptibility are reviewed, as are environmental factors such as the interaction of HRT with alcohol intake. The clinical implication of these data is that the dosage of HRT should be the smallest that is efficacious. Subcutaneous implants of oestrogen typically cause very high oestrogen levels and, in the opinion of this reviewer, should be restricted to women unable to take or absorb oestrogen by mouth or percutaneously. Finally, the issue of HRT for women with a history of breast cancer is considered. The potential is discussed for treatment of women with severe symptoms of oestrogen deficiency with a low dose of oestrogen, together with a selective oestrogen receptor modulator to protect the breast.