Metabolomic and Inflammatory Biomarker Profiling of Radiotherapy-Related Outcomes in Breast Cancer

Breast cancer is the most frequently diagnosed cancer among women in the United States. Although advances in screening and treatments, including adjuvant radiotherapy (RT), have improved survival, RT is associated with acute and long-term toxicities that affect quality of life and clinical outcomes. Variability in RT response suggests underlying biological mechanisms may contribute to differences in treatment outcomes and toxicities. This dissertation explores the role of metabolic and inflammatory biomarkers in RT-related skin toxicities, pain, and breast cancer progression. Data were obtained from a prospective cohort study of breast cancer patients undergoing adjuvant RT at the University of Miami Sylvester Comprehensive Cancer Center and Jackson Memorial Hospital. Global urinary metabolomic profiling was conducted using ultra-performance liquid chromatography–tandem mass spectrometry (UPLC-MS/MS) and gas chromatography–mass spectrometry (GC-MS), and plasma interleukin-18 (IL-18) was measured before and after RT. Early adverse skin reactions (EASRs) were assessed using the Oncology Nursing Society criteria; pain was measured using the Brief Pain Inventory; and disease progression included recurrence, second primary cancer, metastasis, or death. Pre-RT metabolomic profiles were associated with RT-induced EASRs (n = 60), including pathways such as alanine, aspartate, and glutamate metabolism (impact = 0.60; FDR p = 0.0028). Post-RT metabolomic profiles were associated with disease progression (n = 120), including amino acid metabolism (impact = 1.00; p = 0.0007), histidine metabolism, and markers of carbohydrate metabolism and oxidative stress. Elevated pre-RT IL-18 was associated with increased odds of post-RT pain (OR = 2.36, 95% CI: 1.15–4.87) and RT-related pain (OR = 2.73, 95% CI: 1.20–6.26), particularly among patients with obesity. Overall, RT-induced inflammatory and metabolic responses may contribute to toxicities, pain, and disease progression, informing risk stratification and precision medicine strategies.