The mission of the Early Detection Research Network (EDRN) is to translate newly emerging molecular knowledge into practical clinical tests to detect cancer and to more accurately evaluate cancer risk. Fox Chase Cancer Center is responding to the RFA to establish a clinical epidemiology and validation center (CEVC). Fox Chase will serve as a resource center for specimens for use in collaborative research. In order to establish a CEVC we propose: 1) To assemble a multidisciplinary team of investigators focused on early detection and risk assessment markers. 2) To develop meaningful collaborations with other EDRN centers and with regional institutions to foster early phase studies. 3) To establish procedures for study monitoring, managing protocols/projects as well as quality assurance and data sharing. 4) To participate in steering committee activities and respond to steering committee proposals and suggestions. 5) To assure subject safety and to protect information acquired on participating subjects. Fox Chase Cancer Center proposes a research plan for clinical biomarker validation studies for early detection of breast cancer utilizing proteomic techniques developed at Fox Chase Cancer Center and capability of detecting DNA hypermethylation in serum in patients at high risk for cancer. FCCC will use its unique resources 1) to assess the accuracy of biomarkers in predicting extent or severity of disease. 2) to evaluate gene environmental interactions. 3) to understand risks and susceptibility in high risk cohorts and 4) to identify and work with unique high risk populations that are enrolled in Fox Chase affiliated registries and tumor banks.