Mitigating Cardiotoxicity: The Effects of Physical Activity on Echocardiographic Parameters and the Metabolome in Breast Cancer Patients Receiving Anthracycline Treatment

Abstract

Metabolomic profiling is a novel technique to identify anthracycline-induced cardiotoxicity (CTX). Higher physical activity levels may mitigate this damage. Therefore, the primary objectives of this thesis were to determine the effects of anthracyclines on the metabolome, investigate the relationship between echocardiographic parameters and the metabolome, and assess the impact of physical activity levels on echocardiographic and metabolic changes. 17 adult females with stage I to III breast cancer scheduled to receive anthracyclines completed baseline and 24-week follow-up assessments. Assessments included an echocardiogram to measure left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), a questionnaire to assess physical activity levels, and a blood draw for the targeted metabolomic analysis. No significant changes in LVEF% (P = .08) or GLS% (P = .07) were identified. Lipids were the most frequently affected metabolite class.The altered metabolites were unrelated to changes in LVEF% (P = .40, R2 = 0.93) or GLS% (P = .34, R2 = 0.94). Baseline levels of physical activity were associated with changes in GLS% (P = .01) and phosphatidylcholine 16:0/16:0 (P = .02). Baseline physical activity levels were also associated with changes in 71% of assessed metabolites compared to follow-up physical activity levels. Follow-up reported physical activity levels impacted changes in urea relative intensity (P = .02). Anthracyclines altered metabolite levels, particularly in lipid-based metabolites. Physical activity levels, notably baseline, were associated with changes in metabolic parameters and GLS%. Changes in the metabolome were not predictive of echocardiographic parameters. Future longitudinal research should be conducted to identify metabolic biomarkers for CTX, and investigate the effect of physical activity, particularly before anthracycline treatment, on CTX development.