Area of interest
Dr. Dorsey's research is focused primarily on the molecular epidemiology and the molecular genetics of breast cancer. One area of study is the identification of somatic alterations in benign breast biopsies that are predictive of subsequent breast cancer. Through collaboration with the Mayo Clinic, we are evaluating benign breast biopsies and subsequent malignant breast tumor tissues taken from subjects who were part of a large cohort of women who underwent benign breast at the Mayo Clinic during the 1960s and were followed for the development of breast cancer. Women who developed breast cancer became cases, while women who remained free of cancer served as controls. Benign and malignant tissues are being screened for molecular or immunohistochemical changes including p53 mutations or overexpression, HER-2/neu amplification or overexpression, expression of estrogen receptors (ER) alpha and beta, and a point mutation (A908G) in ER alpha.
Studies are also ongoing to assess somatic genetic alterations in breast tumors from the Carolina Breast Cancer Study (CBCS), a population-based, case-control study of invasive breast cancer in North Carolina. We have screened nearly 750 breast tumors from the CBCS for mutations in exons 4-8 of the p53 gene, making this one of the largest studies of p53 in breast cancer to date. The prevalence and spectrum of p53 mutations is being evaluated in relation to potential risk factors for breast cancer, including cigarette smoking, as well as clinical and tumor characteristics. Within the CBCS, we are determining if certain etiologic subsets of in situ and invasive breast cancer are defined by markers of estrogen receptor signaling, including expression of ER-alpha and ER-beta, and the ER-alpha A908G point mutation, or hormone metabolizing enzyme genotypes. The relationship between the presence of somatic ER markers, breast tumor histologic or clinical characteristics, hormonal risk factors and genotypic variation in hormone metabolizing enzymes will be evaluated.
Awards and Honors
Within the Mayo Clinic benign breast disease study, women who had both HER-2/neu amplification and a proliferative histopathologic diagnosis in their benign biopsy were found to have an eight-fold increased risk of developing breast cancer. P53 mutations were also identified in some benign biopsies. Current work is focusing on the detection of ER mutations in benign and malignant breast tissues of this data set.