Mechanism of Cardiac Energy Metabolism Disturbance Induced by EC-T Sequential Chemotherapy After Breast Conserving Surgery in Stage I–II Breast Cancer Patients: A Prospective Cohort Study

Background: This study is a prospective cohort study that aimed to explore the mechanism involved in myocardial energy metabolism disturbance in breast cancer patients with stages I to II. Notably, myocardial energy metabolism disturbance is induced by epirubicin, cyclophosphamide, and paclitaxel taxane (EC-T) sequential chemotherapy after breast-conserving surgery. Methods: Stage I and stage II breast cancer patients treated in the breast or oncology departments of the hospital from February 2021 to May 2023 were invited to participate in the study. The patients were treated with EC-T sequential chemotherapy after breast-conserving surgery. The patients were divided into a control group (no cardiotoxic event, n = 155) and an observation group (cardiotoxic event, n = 45) based on clinical evaluations and laboratory tests. All patients signed informed consent for the protocol during study inclusion. Two groups were compared for clinically relevant differences. Blood biochemical analyses were performed to detect the levels of myocardial injury and myocardial oxidative stress. Enzyme linked immunosorbent assay (ELISA) was employed to detect serum mitochondrial respiratory enzyme activity. Cardiac magnetic resonance spectroscopy (MRS) was used to detect myocardial energy metabolism. The blood flow and metabolic status of the heart were assessed by positron emission tomography (PET). Results: The general data were identical in the two groups (p > 0.05). The observation group had significantly higher levels of troponin, creatine kinase, creatine kinase-MB (CK-MB) isoenzyme, and lactate dehydrogenase compared with the control group; meanwhile, the activities of complex I, complex III, and complex V were significantly lower (p < 0.05). In the observation group, the levels of adenosine triphosphate and creatine phosphate were lower than those in the control group, while the levels of reactive oxygen species (ROS) and malondialdehyde (MDA) were higher (p < 0.05). The levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in the observation group were lower than those in the control group, while the levels of pyruvate and β-hydroxybutyric acid were higher (p < 0.05). Moreover, cardiac blood flow, myocardial glucose uptake, myocardial fatty acid uptake, and myocardial metabolic efficiency in the observation group were lower compared with the control group (p < 0.05). Conclusions: In breast cancer patients with stages I to II who were receiving an EC-T sequential chemotherapy regimen, myocardial energy metabolism disorders are associated with increased markers of myocardial injury. This phenomenon is associated with decreasing mitochondrial respiratory enzyme activity, changes in energy metabolic pathways, and reduced cardiac blood flow and metabolic efficiency. These results suggest that EC-T chemotherapy may cause direct damage to cardiomyocytes and affect the normal metabolic function of the heart.