Mammographic Density and Invasive Breast Cancer

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DESCRIPTION (provided by applicant): Results from the recently published Women's Health Initiative (WHI) clinical trial have unequivocally confirmed previous epidemiologic data, which suggested that, combined hormone therapy with estrogen and progestin (EPT) increases risk of breast cancer. Although the magnitude of the risk increase is relatively modest, given the high prevalence of EPT use, the attributable number of cases affected is likely to be large. Because the overall risk increase is relatively modest, it is likely that some women are more susceptible to the carcinogenic effect of EPT than others. It would thus be useful to have a clinical biomarker that could be used to identify those high-risk EPT users. The ideal biomarker would be measurable early enough in the course of EPT to allow cessation before elevated risk is expressed as frank disease. Mammographic density (MD) change is a promising candidate for such a marker. Using the infrastructure for film digitization and density measurement developed under a previous WHI ancillary protocol, mammograms from all cases of invasive breast cancer within the EPT arm of the WHI trial will be collected along with 3 controls from the same population, matched by treatment assignment (EPT or placebo), clinical center, and ethnicity. Density changes over the initial baseline mammogram and the first follow-up mammogram after randomization for each participant will be measured. Measurements of MD and risk assessment will be made by four experienced human readers and an automated computer program. The primary aims of this project are to estimate the relative risk for breast cancer associated with a change in MD, to determine whether the increased breast cancer risk associated with MD change is independent of baseline MD, to determine the proportion of breast cancer cases attributable to MD change among women assigned to EPT, and, to determine whether post-EPT MD change explains the increased breast cancer risk associated with EPT within the entire study population. The secondary aims of this project are to measure the difference in relative risk of breast cancer using MD measurements made by four experienced observers and to determine whether relative risk of breast cancer using MD change assessed by an experimental automated computer procedure is comparable to that estimated by four experienced assessors using established thresholding techniques.