Clinical, Analytical, and Echocardiographic Associations of Impaired Cardiorespiratory Fitness After Anthracycline Chemotherapy in Breast Cancer: EPIC Fitness Study

Purpose This study explores the effects of anthracycline chemotherapy (AC) on breast cancer patients, focusing on changes in body composition, advanced echocardiographic parameters at rest and during exercise, and biomarkers; and subsequently assesses whether these parameters are associated with impaired cardiorespiratory fitness (CRF). Methods In this prospective study, we evaluated women with early‐stage breast cancer undergoing AC at three visits: before AC, 1 month after, and 6 months post‐AC. Results The study included 32 women with breast cancer, with functional disability increasing from 9.0% pre‐AC to 43.8% at 1 month and 53.1% at 6 months post‐AC. At 1 month, patients with functional disability exhibited higher rates of cancer therapy‐related cardiac dysfunction (CTRCD) (85.7% vs. 55.5%) and, during exercise, showed lower left ventricular ejection fraction (LVEF), reduced contractile reserve and stroke volume (SV); along with elevated IL‐6, PlGF, and MPO levels. By 6 months, these patients maintained higher CTRCD rates (35.3% vs. 0%), lower SV and cardiac output (CO), reduced global longitudinal strain (GLS), and decreased global work index (GWI). During exercise, they had lower SV; additionally, they exhibited higher MPO levels and increased body and visceral fat. In our multivariable model: age, body fat, resting GWI, exercise LVEF, and CO were independently associated with VO2peak. Conclusion Significant and persistent CRF reductions are common in breast cancer patients post‐AC. While resting LVEF and GLS were not linked to VO2peak, resting MWI and exercise LVEF and CO were, potentially identifying patients at increased long‐term heart failure risk who would benefit from cardioprotective strategies like cardio‐oncology rehabilitation. It is important to recognize that impaired CRF is multifactorial, as demonstrated by age and body fat being independently associated with VO2peak, and the impact of non‐cardiac factors should be better studied. Our findings highlight the need for further research on CTRCD definition, suggesting that CPET and advanced exercise echocardiography could enhance risk stratification.