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.