Full Project 3: Molecular Pathways to Breast Cancer Mortality among African American and White Women

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Abstract Relative to white women, African American women have higher incidence of breast cancer before age 40 and suffer higher mortality at all ages. The Carolina Breast Cancer Study has shown that African American women are more likely to get estrogen receptor negative breast cancer and triple negative or basal-like breast cancers. Furthermore, when African American women get estrogen receptor positive breast cancers, their survivorship is lower than white women with similar disease. To better understand the biological pathways that lead to incidence mortality disparities, we will collect RNA expression data from Carolina Breast Cancer Study tumors. The Carolina Breast Cancer Study Phase 3 is a cohort study of 3000 women with breast cancer, half of which are African American women. The study was conducted in 44 counties and used population-based sampling, therefore representing catchment for the state. Detailed treatment and clinical data are available for survivorship analyses. Aim 1 will use RNA expression levels to classify participants according to tumor gene expression in crucial biologic pathways: estrogen responsiveness among luminal breast cancers, hepatocyte growth factor (HGF)-signaling among basal-like breast cancers, and immune response pathways in all subtypes. Aim 2 will link heterogeneity in tumor gene expression with exposure to breast cancer risk factors. Finally Aim 3 will link tumor gene expression with cancer outcomes. Novel data collected in this application will be combined with existing data on other important breast cancer pathways (e.g. intrinsic subtype, p53 expression subtype, EGFR signaling, hypoxia signaling, etc.) to develop a complete picture of the biology of breast cancer disparities. This project will also support an NCCU-UNC partnership by extending successful methods developed in the UNC Breast Cancer Specialized Program of Research Excellence, and transfering this knowledge to support our Lineberger-NCCU partnership. UNC Lineberger has a state-wide mission, a top ranked school of public health, and an outstanding medical school. Partnership-recruited faculty and trainees will gain expertise in research methods and technology not typically available on a campus without these health sciences strengths. Thus, while the research addresses a health disparity, the implementation of the project will also address a gap faced in conducting high impact public health and clinical/translational work at NCCU. This project will have both an important disparities and partnership endpoints.