Since the establishment in 1995, the Breast Cancer Family Registry (Breast CFR), an international consortium of six collaborating sites, has enrolled over 13,000 families across a wide range of breast cancer risk. The Northern California Family Registry for Breast Cancer (NC-FRBC) has contributed significantly to the resource and collected high-quality data on family history, epidemiologic risk factors and dietary intake, as well as biospecimens for over 2,600 families, including 1,900 minority families, which account for 70 percent of all enrolled minority families. The NC-FRBC brings many strengths to the Breast CFR, such as experienced leadership and collaborative partners, population-based sampling, targeted recruitment of minorities, new analytic methods, and successful data utilization. The objectives of this 5-year renewal grant are to: 1) establish and maintain a hypothesis-driven research infrastructure to expedite and implement collaborative, multi-disciplinary and multi-institutional research in genetic epidemiology of breast cancer; 2) re-structure the current infrastructure into nine Core Platforms and maintain and further enhance the existing resources; and 3) recruit an additional 830 population-based minority families (470 Hispanics, 360 African Americans). Core activities associated with each Platform include: a) conduct a systematic follow-up of probands and relatives enrolled from 1995-2005, and continue annual follow-up of all probands enrolled from 1995-2009; b) expand data and biospecimen collection in families of special interest (i.e., multiple case early-onset and BRCA1 and SRC/42 mutation carriers); c) expand clinical and prognostic data collection on probands and affected relatives; d) expand tumor block collection to construct tissue microarrays, e) enhance existing biospecimen resources and establish a duplicate repository; f) expand BRCA1 and BRCA2 mutation testing; g) maintain and enhance local informatics capabilities; h) contribute to resources to facilitate behavioral and psychosocial research; and i) coordinate internal registry functions and collaborations with Breast CFR and external investigators. This enhanced and expanded resource will facilitate a broad spectrum of research, ranging from identification of genetic factors related to breast cancer risk and their interactions with environmental and other genetic modifiers, to translational studies addressing clinical, behavioral and preventive aspects of breast cancer.