Associations Between Fatigue and Cellular Metabolism in Breast Cancer Patients: A Longitudinal Study

Purpose: Fatigue is frequently experienced during treatment for cancer and persists for months to years after treatment completion in a subset of patients. The underlying mechanisms remain poorly understood. We postulated that reduced cellular energy metabolism may underlie fatigue in cancer patients and survivors and tested this hypothesis in a sample of patients newly diagnosed with early-stage breast cancer (n = 49) followed for approximately 1 year from before the start of neoadjuvant chemotherapy (NACT) till after treatment completion. Methods: Patient-reported fatigue was assessed with the Checklist Individual Strength, and blood samples were obtained before, during, and shortly after NACT. A final assessment was completed after surgery and radiation therapy, 4-6 months after NACT. At each study time point, mitochondrial oxygen consumption and glycolytic activity were measured in peripheral blood mononuclear cells (PBMC). Associations of these measures of PBMC energy metabolism with fatigue were assessed in multilevel models. Results: Before NACT, higher mitochondrial oxygen consumption and glycolytic activity were associated with higher fatigue, whereas after completion of all primary treatment, these assessments were associated with lower fatigue. Conclusion: These findings suggest that lower cellular energy metabolism after treatment may be a novel target for interventions aimed at preventing or reducing persistent fatigue. Earlier studies investigated the use of supplements for maintaining mitochondrial health during treatment, with mixed results; when proven to be safe, such interventions may be more effective after treatment and in individuals with reduced mitochondrial oxygen consumption rates.