Epidemiologic studies find that increased mammographic density is an independent risk factor for breast cancer and the magnitude of risk associated with mammographic density is greater than that associated with almost all other known risk factors for breast cancer. This application focuses on 3 major questions: 1) are endogenous levels of sex steroids in postmenopausal women related to mammographic density; 2) does treatment with postmenopausal estrogen and estrogen/progestin therapy increase mammographic density; and 3) do the serum levels of estrone achieved as a result of treatment with postmenopausal hormone therapy predict change in mammographic density? To address these questions, the amount of density of mammograms performed during the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial will be determined using a computer-based threshold technique. PEPI was a 3-year, randomized placebo controlled trial of conjugated equine estrogens (CEE) vs. CEE plus one of 3 progestin regimens, which enrolled 875 postmenopausal women aged 45-64 at baseline. Data already collected as part of PEPI that will be used in this project will include: endogenous sex steroids at baseline, PEPI treatment assignment, estrone serum levels on-treatment, and necessary covariates. The project will last 3 years and take place at 3 sites: UCLA, USC, and Bowman Gray.
The specific aims are to: 1) measure the density of mammograms performed at baseline and 12 months; 2) determine whether baseline mammographic density is associated with endogenous levels of sex steroids; 3) quantify the relation between change in mammographic density and adherence to treatments; and 4) determine whether changes density are associated with serum levels of estrone achieved as a result of hormone therapy. By assessing density changes in mammograms with this computer-based method, which has been previously linked to a quantified increase in risk of breast cancer, it may be possible to assess how much of a risk-increase would be predicted by hormone use. The investigators state that this may serve as the first in a series of investigations that would allow identification of those women at higher risk of developing breast toxicity from postmenopausal supplemental hormone use.
