Genetics of Mammographic Appearances and Patterns (The GenMap Study)

High mammographic density (HMD) is the strongest risk factor for non-familial breast cancer apart from age and gender. Studies of sisters and twins suggest that approximately 67% of the variation in density is attributable to common genetic factors. However, to date, efforts to identify genetic determinants of HMD have achieved limited success. We and others (Boyd et al Lancet Oncol 2009) postulate that this lack of progress in identifying genetic determinants of density is related to a failure to study younger women and misclassification of density. As women age, their breast tissues undergo atrophy, which is manifested radiologically as a decrease in mammographic density, resulting in a convergence of density values and a masking of inter-person variation. This protocol is intended to demonstrate the feasibility of methods that we plan to use in a full-scale analysis of mammographic density among women under age 50 years who receive care at the University of Vermont, Fletcher Allen Health Care (FAHC) and have been followed through the Vermont Breast Cancer Surveillance System (VBCSS). The Hormonal and Reproductive Epidemiology Branch (HREB) is currently conducting a cross-sectional study entitled, Breast Radiology Evaluation and Study of Tissues (BREAST) Stamp Project which aims to understand why mammographically dense tissues are related to elevated breast cancer risk. This project is being conducted within the VBCSS using breast cancer awareness Stamp Act funds. The BREAST Stamp project has focused on women between the ages of 40-65 years who were referred for radiologically-guided biopsy to evaluate an abnormality identified on a screening mammogram. The study has successfully enrolled over 400 women with collection of questionnaires, buccal and blood samples, and tissues. The study will continue recruiting through May 2010, with a targeted enrollment of 450-500 women. Through the infrastructure developed for the BREAST Stamp Project, mammographic volumetric d