Abstract 9092: Association of Biomarkers of Oxidative Stress, Inflammation, and Cardiac Damage with Long-Term Radiation-Induced Cardiovascular Outcomes in Breast Cancer

Introduction: Radiation therapy (RT) is a common component of breast cancer (BC) management, but may be associated with radiation-induced cardiovascular disease (RICVD) which includes coronary heart disease, myocardial infarction, CVD death, heart failure, or stroke. We examined associations of biomarkers of oxidative stress (MPO, GDF-15, 8-OH-dG, PGF), cardiac injury (TnI, Cystatin-C), inflammation (IL-6, CRP), and myocardial fibrosis (TGF-B) with long-term RICVD in BC survivors. Methods: In an ancillary, nested case-control study within the Women’s Health Initiative, postmenopausal women with incident BC stages I-III, who received RT, and had pre- and post-BC diagnosis serum samples available not more than 3 years apart were eligible. Cases were defined as developing incident, physician-adjudicated coronary heart disease, myocardial infarction, CVD death, heart failure, or stroke after BC. Each case was matched to 3 controls on enrollment age and visit year of pre-BC blood draw. Biomarkers were analyzed using enzyme-linked immunosorbent assays and modeled as the post-BC to pre-BC ratio and log transformed to base 2. Logistic regression models were adjusted for demographic, lifestyle, and cancer characteristics. Results: A total of 55 cases and 158 controls were included with a mean (SD) age of 66.9 (5.5) years and a median (IQR) time from BC diagnosis to post-BC serum collection of 1.4 (0.7, 2.4) years. After adjustment, a higher 8-OH-dG ratio was significantly associated with an elevated risk of RICVD (Table). For a doubling in the biomarker ratio, RICVD risk was 3.04-fold higher (95% CI: 1.01, 9.21). Other biomarkers were not associated with RICVD risk. Conclusions: In this study, higher concentrations of 8-OH-dG were associated with a higher risk of RICVD. This suggests that oxidative DNA damage may be a putative pathway for delayed RICVD. However, given the sample size and multiple testing, further studies are needed to confirm or refute these findings.