The principal goal of this proposal is to develop a cohesive, multidisciplinary breast cancer program at the City of Hope Cancer Research Center (COH). From 1985 to 1992 (the last calendar year for which definitive data are available), the breast cancer population increased from 15 to 25% of the entire cancer patient population at COH; in absolute terms, this represented an increase from 242 to 478 new breast cancer patients evaluated per year. Patients with breast cancer now embody the single most common diagnosis treated at our institution. This increase in patient volume has been accompanied by a remarkable increase in the extent of breast cancer-related clinical and laboratory research at the COH. Thus, it is appropriate to propose to develop the infrastructure to support a new Cancer Center program that will focus on interactive, investigative basic, clinical, and cancer control initiatives in breast cancer. The goals of the developing COH Breast Cancer Research Program are: (1) to complete innovative clinical trials in patients with breast cancer in the areas of gene therapy, radioimmunotherapy, high-dose chemotherapy with autologous peripheral blood progenitor cell rescue, biochemical modulation, and drug resistance reversal; (2) to perform pre-clinical studies of novel gene delivery systems and gene-directed breast cancer therapies, new monoclonal antibodies against the carcinoembryonic antigen as well as other breast cancer antigens, and the molecular pharmacology of breast cancer drug resistance aimed at the continuing development of new therapeutic agents for this disease; and (3) to investigate the molecular events leading to breast carcinogenesis and improve the diagnosis and control of breast cancer. Based on the availability of a large patient resource, a proven track record of accrual to complex, innovative institutional breast cancer clinical trials, and a strong history of productive basic and clinical research interactions in molecular pharmacology, molecular immunology, tumor biology, virology, and cancer control that have been applied directly to enhance the therapeutic outcome for patients with breast cancer, we propose to unify breast cancer research at the City of Hope. The growth and maturation of the COH Breast Cancer Research Program will focus the interests and facilitate the development of a strongly interactive research team with the potential to make an important contribution to the reduction of breast cancer incidence and mortality.