Radiation-Induced Cardiovascular Disease and Fatigue in Breast Cancer Survivors: Understanding Biological Mechanisms and Risk Factors

Abstract

Although survival rates have improved, many breast cancer survivors experience adverse effects related to the physiologic consequences of cancer treatment including an increased risk cardiovascular disease (CVD) and symptoms, such as fatigue. Currently, it is not known how to best identify breast cancer survivors at risk for CVD and fatigue. Cancer treatments are known to be associated with both CVD and fatigue independently. At the same time, cardiotoxicity and fatigue may share common physiologic mechanisms such as chronic inflammation and oxidative stress, which directly target cardiac tissue to produce CVD and produce circulating inflammatory markers that may lead to fatigue. It is hypothesized that cancer treatments, through the complex relationship with oxidative stress and inflammation, create a pro-fibrotic environment, which contributes to heart disease and heart failure. While cancer treatments can independently cause fatigue, fatigue is also a commonly reported symptom in patients with heart failure, coronary artery disease, pericardial disease, and valvular disease, which are all potential cardiovascular outcomes associated with radiation treatment. Therefore, it is not only important to examine the association between inflammatory and oxidative stress biomarkers and fatigue but also look at cardiac damage and fibrosis markers in persons who have received radiation treatment. Additionally, there is evidence in non-cancer populations that fatigue itself, and other symptoms associated with cancer treatments, are associated with the risk of CVD. Therefore, the overall purpose of this dissertation is to better understand risk factors for CVD and symptoms after cancer treatment in breast cancer survivors and to better understand how these factors relate to one another. Specifically, this dissertation has the following aims: 1) to assess the association of post-cancer biomarkers and CVD events in breast cancer survivors treated with radiation; 2) to examine the associations of post-cancer biomarkers and post-cancer fatigue in breast cancer survivors treated with radiation; and 3) examine whether physical and mental health-related quality of life (which incorporates a measure of fatigue) or sleep disturbances scores are associated with CVD risk in breast cancer survivors.