PEPI Study Research has shown that women 45 years or older who have at least 75 percent dense tissue on a mammogram are at elevated risk of developing breast cancer. Reasons for this are not yet understood. Studies, including the Post-menopausal Estrogen/Progestin Interventions (PEPI) trial, show that about one fourth of women who use hormone replacement therapies (HRT) that include progestin have an increase in breast density on their mammograms. In the PEPI trial a smaller number (about eight percent) of women taking estrogen-only therapies also had increased breast density. It is not known if increased breast density due to HRT carries the same risk as having naturally dense breasts, but it does make it more difficult for a radiologist to read some mammograms. Such a reduction in readability could lead to about a 30% increase in follow up mammography studies and an increase in breast biopsies. One retrospective study showed that short-term cessation of HRT improves mammographic accuracy. A prospective study is needed to explore the value of this strategy. Recent evidence suggests that women who have long term exposure (more than 10 years) to hormone replacement therapy may have a slightly increased risk of developing breast cancer. It is not known if this increased risk is linked to increased breast density or to other factors. Every woman must evaluate the risks and rewards of estrogen replacement therapy and should consider both its impact on mammography as well as potential cardiovascular and bone density benefits. An article describing the PEPI research conducted by the National Heart, Lung, and Blood Institute (NHLBI), titled "The Effects of Estrogen and Estrogen/Progestin Treatments on Mammographic Parenchymal Density," appeared in the February 1999 issue of the Annals of Internal Medicine.
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