Clinical Cancer Genetics, Cancer Risk, and Prevention
Our group has two areas of active interest: the identification of individuals with genetic factors that place them at high risk of developing cancer, and the development of strategies to reduce cancer risk. We focus on breast cancer primarily, but are now expanding our efforts to other cancers. Breast cancer geneticsOur group developed one of the first cancer risk and prevention clinics, where we recruit patients and families with hereditary and familial breast cancer, evaluate them for mutations in BRCA1, BRCA2, and other genes, and then enroll patients in ongoing follow-up studies. These studies evaluate the long-term psychosocial and medical effects of genetic testing and explore the best ways to integrate genetic testing into the care of women diagnosed with breast cancer. We are also studying the prevalence of germline p53 mutations and mutations in the Fanconi anemia (FA) genes in a cohort of the very youngest women diagnosed with breast cancer. In collaboration with Dr. Alan D'Andrea, we also plan to expand epidemiologic studies of the FA genes to squamous tumors. Breast cancer risk reductionWe are developing novel approaches to the chemoprevention of cancer and the identification of modulatable biomarkers for use in chemoprevention studies. One clinical trial uses aromatase inhibitors to reduce circulating estradiol in women who have the highest levels, and measures changes in bone density and mammographic breast density as biomarkers of hormone effect. Another trial is piloting tamoxifen in women with increased risk of breast cancer because of chest radiation therapy for Hodgkin's disease. In collaboration with Drs. Myles Brown and Bruce Spiegelman, we are developing biomarker assays for use in the evaluation of rosiglitazone in an early-phase breast cancer chemoprevention trial. In a phase I chemoprevention trial, we are studying the epidermal growth factor receptor (EGFR) antagonist, Iressa. Finally, we are developing duct lavage as a sampling technique with which to identify modulatable biomarkers for use in breast cancer chemoprevention trials.PharmacogeneticsWe are also interested in using genetic markers to identify individuals at particular risk for toxic side effects of chemoprevention agents. Two large national trials are evaluating the potential contributions of hereditary clotting abnormalities, factor V Leiden and prothrombin G20210A, to the risk of thromboembolic complications with tamoxifen.