Hormone therapy, mammographic density, and breast cancer risk.

Percent mammographic density (PMD) is a strong independent risk factor for breast cancer. The effects of age, parity and menopause on PMD are consistent with it being a marker of susceptibility to breast cancer. In this review, we describe the association of PMD with breast cancer, the biological plausibility of this association, and discuss the extent to which PMD meets the criteria for a surrogate marker for the effects of exogenous hormones on risk of breast cancer. Combined hormone therapy is associated with a small increase in both PMD and the risk of breast cancer. However there is evidence that the associations of blood estradiol levels and HRT with breast cancer risk are independent of the association of PMD with risk, suggesting that different biological pathways may be involved. Tamoxifen, an anti-estrogenic drug, reduces both the risk of breast cancer and PMD, but the potential mediation of the effects of anti-estrogens on breast cancer risk by their effects on PMD has not yet been examined. Given the evidence that estradiol and PMD are independently associated with breast cancer risk, it seems unlikely that an effect of these agents on PMD mediates their effects on risk. We thus find that the available evidence is insufficient to conclude that PMD can be used as a surrogate marker for the effect of exogenous hormones on breast cancer. Further research to examine the potential role of PMD as a mediator of the effects of other risk factors is required.