Hormone replacement therapy and risk for breast cancer

Because breast cancer will develop in one of every nine American women, even a small increase in risk associated with a widespread exposure is of substantial public health concern. Although most studies have not found ever use of estrogens to be a risk factor for breast cancer, it is not yet resolved whether current or long-term users experience some increase in risk. Given the fact that the indications for menopausal estrogen use have changed substantially over time, from short-term use for the relief of menopausal symptoms to long-term use for lifetime reduction of conditions such as cardiovascular disease and osteoporosis, it is imperative that the effects of long-term estrogen replacement on the risk for breast cancer be resolved. These studies are not without associated methodologic difficulties, with the ultimate interpretation of the association possibly dependent on the results of controlled clinical trials. Although such investigations are currently underway, the results will not be available for many years. To address more immediate concerns, continued emphasis should be placed on well-designed case-control and cohort studies. For the results to be reliable, attention must be directed to the effects of selection, recall and surveillance biases, confounding factors, detailed exposure relationships, subgroup variations, and disease associations. In addition, given the increasing trend for estrogens to be prescribed in combination with progestogens, the effects on breast tissue of this combined therapy merit immediate attention.