Abstract
Abstract Objective: To assess the prognostic significance of molecular biomarkers, particularly metabolic and Inflammatory pathways using samples from a prospective study of breast cancer patients undergoing adjuvant radiotherapy (RT). Methods: We used ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) for measuring urine metabolites. Following normalization to osmolality, log transformation, and imputation of missing values, we used Welch’s two-sample t-test to identify biochemicals that differed significantly by progression status. We measured pre- and post-RT plasma high-sensitivity C-reactive protein (hsCRP) levels. Progression-free survival (PFS) was calculated from the date of diagnosis to the date of disease progression or last follow-up. Univariable and multivariable Cox proportional hazards regression models assessed the associations between hsCRP and PFS. Results: In 120 breast cancer patients, carbohydrate metabolism, branch-chain amino acid (BCAA) metabolism, phosphatidylcholine metabolism, arginine metabolism, oxidative stress-related metabolites, androgenic steroids, and nucleotide metabolism had the most notable differences in patients with progression versus progression-free cases. In 488 breast cancer patients, RT significantly increased plasma hsCRP levels, and post-RT hsCRP levels were significantly higher in deceased vs. alive patients (p=0.031). In multivariable models, hsCRP had a prognostic value for all-stage and stage 0-II patients. Conclusions: In our study of breast cancer patients receiving adjuvant RT, multiple metabolite biomarkers and post-RT plasma CRP levels were associated with a worse prognosis. BCAAs and fatty acids regulate cell metabolism by affecting mitochondrial function and inflammation signals. Thus, our findings suggest a potential role of metabolic and inflammatory pathways in breast cancer prognosis. These molecules may have potential utility as prognostic biomarkers for breast cancer patients undergoing adjuvant RT and targets for intervention. Keywords: breast cancer, metabolomics, inflammation, prognosis Citation Format: Alexandra N. McMahon, Cristiane Takita, Jean L. Wright, Isildinha M. Reis, Eunkyung Lee, George Yang, Jennifer J. Hu. Prognostic biomarkers for breast cancer: Metabolic and inflammatory pathways [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 5212.