Researchers at Duke University Medical Center will collaborate and share resources to create a Specialized Program of Research Excellence (SPORE) in Breast Cancer. Each of the major projects are at the leading edge of research and clinical practice. The search for BRCA1, a heritable breast cancer gene on chromosome 17, ended in August of 1994. In collaboration with investigators at the National Institutes of Environmental Health Science (NIEHS), Project 2 will investigate the function and regulation of wild-type BRCA1 and examine the occurrence of mutations in breast and ovarian tissue. Finding that BRCA1 is estrogen regulated connects this project to Project I which will investigate genes induced by estrogen agonists and antagonists in the breast and endometrium. A system will be developed to screen and test new chemopreventives based upon transactivation of estrogen responsive genes. We believe BRCA1 is such a gene and perhaps mitigates the mitogenic effect of estrogen in the breast. Testing for mutations in BRCA1 will be handled in a stepwise and measured fashion by Project 3. Investigators will assess the intentions and beliefs of women with breast cancer and their relatives, intervene with a clinical trial of tailored consent information, and measure psychosocial effects following testing. Project 4 is pivotal between the first projects and later investigation of novel treatments for established breast cancer. A team of investigators from biostatistics and health policy backgrounds will create interactive and useful tools to assist decision making at all echelons of breast cancer, from risk assessment through treatment. Project 5 will measure tumor-associated and circulating cytotoxic T cells recognizing defined and genetically cloned tumor antigens. Clinical phase I trials of active and adoptive immunotherapy will be conducted during the second and third years, drawing from patients in our Bone Marrow Transplant Program and Multidisciplinary Clinic. The Developmental Program is unique and will fund four established investigators to translate mature basic investigations into novel therapeutic strategies for breast cancer. Two projects concern angiogenic inhibitors, a second will develop targeted liposome carriers, and the final project will study mechanisms of topoisomerase inhibition. Core Resources are a DNA sequencing and family ascertainment facility in Core #1, Biostatistics and Data Management in Core #2, and Administration in Core #3. Career deveLopment will permit recruitment of the molecular geneticist who identified the BRCA1 gene. This SPORE complements both a funded P2O Planning Grant, which includes a pilot projects initiative, and a funded Breast Cancer tissue resource.
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