The role of mammographic density in evaluating changes in breast cancer risk.

The Women's Health Initiative (WHI) study showed that postmenopausal continuous combined estrogen-progestogen therapy (EPT) significantly increases the risk of breast cancer, thus confirming the results from large epidemiological studies. These results were predicted approximately 15 years previously based on the epidemiology of breast cancer and the relationship of ovarian hormone levels to breast cell proliferation. However, the prediction had little effect on prescribing habits due to its theoretical nature. Many questions remain regarding menopausal therapy and breast cancer risk, especially the effects of other schedules and regimens. Epidemiological case-control studies and randomized clinical trials with breast cancer as the outcome cannot answer these questions in an appropriate timeframe. Some intermediate marker of breast cancer risk must therefore be used as a basis of rational prescribing. There is considerable evidence in support of using changes in mammographic densities as such a marker. For example, measurement of changes in mammographic density in the Postmenopausal Estrogen/Progestin Interventions (PEPI) trial showed that EPT was likely to be associated with a notably greater risk than estrogen therapy alone, that sequential EPT regimens are likely to increase the risk as much as continuous regimens (if the total progestin dose is similar), and that replacing medroxyprogesterone acetate with progesterone is unlikely to significantly alter the additional risk.