Candidate: Peter Gann is a physician-epidemiologist who has recently redirected his career into full time research on cancer prevention. His current work entails developing markers in tissue, plasma and other fluids to enhance the power and biological relevance of epidemiologic studies on breast and prostate cancer risk. The proposed award will enable him to obtain additional training/expertise in cell and molecular biology while developing into an independent investigator capable of integrating new laboratory techniques with conventional epidemiology. Environment: The primary sponsor for this award is Dr. V. Craig Jordan, Director of Breast Cancer Research at Northwestern University's Lurie Cancer Center. The Co-sponsor is Dr. Philip Greenland, Chair of the Department of Preventive Medicine. These sponsors will guide Dr. Gann's progress and provide access to laboratory facilities and opportunities for cancer biology training. The Department of Preventive Medicine, in which Dr. Gann has his primary appointment, has several established investigators in chronic disease epidemiology. In 1994, the Breast Cancer Program was awarded Federal funding for its research and training objectives. Research: The proposed studies evaluate a) breast fluid from nipple aspirates, and b) normal breast tissue from biopsy samples as sources of intermediate biologic markers. We hypothesize that growth factor (GF) levels in breast fluid reflect the impact of environmental influences (both hormonal and non-hormonal) on the basic growth-regulating mechanisms of the epithelial cells and thus reflect the risk of developing breast cancer. The breast fluid studies (Project 1) aim to: i) identify the relative quantities of major GFs (TGF-alpha, TGF-Beta, IGF-1, EGF) in these fluids, ii) evaluate the extent of and reasons for intra-individual variation in GF level, iii) determine the relations among fluid GF, tissue GF and histology in biopsied patients, and iv) estimate associations between GF level and known or suspected risk factors for breast cancer. The second project examines the association between reproductive and hormonal variables linked to breast cancer and the degree of lobular differentiation in normal breast tissue. We hypothesize that certain "high-risk" profiles will be associated with less mature lobular development. In well-established rodent models, terminal differentiation strongly reduces the susceptibility of mammary tissue to carcinogens. Dr. Gann is working with Dr. J. Russo at the Fox Chase Cancer Center to develop a simple technique for categorizing the differentiation status of lobules in normal, paraffinized tissue from patients with excision biopsies. Later studies will relate differentiation status to tissue and breast fluid of concentrations and to actual breast cancer occurrence. Dr. Gann will assume central responsibility for the design, monitoring, analysis and reporting of both projects, and will be directly involved in all laboratory work.