Abstract B022: Understanding and addressing disparities in cancer therapy induced inflammation and associated endothelial dysfunction

Abstract

Abstract Nearly 4 million breast cancer survivors live in the United States (U.S.). Continued improvements of cancer therapies (CTx), including targeted treatment options such as anti-HER2 therapy combined with traditional systemic CTx like anthracyclines (ANTs) have made adverse cardiovascular events the leading cause of non-cancer related mortality among BC survivors. Toxicities can be acute and/or reversible (e.g., anti-her2) or may persist for years (ANTs)). Most efforts focus on managing and defining the mechanism of cardiac damage in response to CTx. Yet, systemic vascular function, including microvascular endothelial function, is not only a predictor but also a contributor to a significant number of cardiovascular complications that is mostly overlooked in response to CTx. Little to no mechanistic evidence exists how CTx impacts the human circulation and endothelial function. Systemic inflammation (e.g., Interleukin levels or TLR signaling) is elevated in cancer and CV disease alike, yet the connection of CTx induced endothelial dysfunction has not been explored in breast cancer patients. Black/African American women are at higher risk for cardio-toxicity. Existing literature suggest significant racial differences in immune signaling and microvascular function perhaps explaining varying risk for CV toxicity post-CTx. However, contributing biological, social and environmental factors remain ill defined. The Discovery and Elimination of Cardio-Oncology Disparities for Equity (DECODE) in the Heartland center addresses critical gaps in the literature by testing if an exercise intervention can lower systemic inflammatory load to improve endothelial function and CV risk itself. We propose to: 1) quantify physiological and molecular differences in inflammation and endothelial function before and following CTx among 120 Black/African American and non-Hispanic White women with invasive, non-metastatic BC; 2) test the feasibility and efficacy of an exercise intervention during CTx designed to mitigate the adverse effects of treatment on exercise capacity and QoL; and 3) examine the influence of multi-level socio-ecological factors (individual, interpersonal, institutional, environmental) on inflammation, microvascular endothelial function, QoL and response to the exercise intervention among participants. This presentation presents DECODE’s novel translational study design and methodologies. Citation Format: Melinda Stolley, Andreas Beyer, Kirsten Beyer, Alison Kriegel, David Gutterman, Shane Phillips, Sherry Ann Brown, Kent Hoskins, Rodney Sparapani, Michael Widlansky, Amanda Kong. Understanding and addressing disparities in cancer therapy induced inflammation and associated endothelial dysfunction [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B022.