Abstract / Description
Background and aimsThe objective of this study was to define the relationships between the circulating proteome and metabolome with cardiac structure and function in patients with breast cancer receiving cardiotoxic therapies.MethodsProteomics and metabolomics profiling was performed in a longitudinal, prospective cohort study of breast cancer patients receiving anthracyclines and/or trastuzumab, using the Olink Explore 3072 platform and rapid liquid chromatography-mass spectrometry, respectively. Multivariable linear mixed-effect models evaluated the contemporaneous (same visit) and lagged (subsequent visit) associations between repeated measures of individual proteins or metabolites with quantitative echocardiographic measures of cardiac structure [left ventricular (LV) mass and left atrial volume index] and function [LV ejection fraction (LVEF), longitudinal and circumferential strain, E/e', and ventricular-arterial coupling]. Cox regression and pathway enrichment analyses were conducted for biomarkers demonstrating significant associations with cardiac function.ResultsAcross 547 breast cancer participants (median age 50 years), 203 unique proteins and 16 unique metabolites were significantly associated with measures of cardiac structure and function in contemporaneous and lagged analyses. Notably, cathepsin C was associated with LVEF [false discovery rate (FDR), P = .017], longitudinal strain (FDR, P = .046), left atrial volume index (FDR, P = .035), and incident cardiac dysfunction, defined by an LVEF decline ≥10% to