The long-term objective of our research plan is to reduce the disproportionate effects of breast cancer on African American women, especially those belonging to the Triple Negative subtype (i.e., ER-, PR- and Her2-). A guiding principle of our methodology is biochemical differences exist between TN breast cancers of African American and European American origin and that these differences can explain, in part, breast cancer health disparity. In this application, we propose characterization one such alteration in Kynurenine metabolism. High levels of the metabolites Kynurenine and Tryptophan were found in a subset of TN breast cancers, predominantly African American, with poor clinical outcome. These patients also showed higher expression of the RAS oncogene. Based on these we hypothesize that higher levels of the metabolite Kynurenine in association with RAS signaling, could lead to aggressive tumors within the African American women, having TN breast cancer. Further, we propose that characterization of the role of Kynurenine metabolism in TN African American breast cancer could help address the issue of racial disparity in breast cancer clinical outcomes.
Disparity exists between African-American and European-American women, in the clinical outcome of Triple Negative Breast Cancer. At present, the biological mechanisms, underlying the disparity are not well defined. The information gleaned from this proposal could rapidly revolutionize current prognostic and therapeutic approaches by revealing the biological underpinnings associated with Triple Negative Breast Cancer Disparity.
