Breast cancer-related fatigue: Mechanisms, biomarkers, risk factors, and intervention strategies

Breast cancer-related fatigue (BCRF) is a prevalent and debilitating condition that affects patients during and after treatment. It is characterized by persistent, distressing physical and psychological exhaustion that is disproportionate to recent activity and unrelieved by rest. This review synthesizes current evidence on the pathogenesis, biomarkers, risk factors, and intervention strategies for BCRF. Mechanistically, BCRF arises from a complex interplay between inflammation, hypothalamic-pituitary-adrenal (HPA) axis dysregulation, mitochondrial dysfunction, neuromuscular impairment, and psychosocial influences. Multiple biomarkers, including cytokines, cortisol, leptin, and mitochondrial DNA, offer diagnostic and prognostic potential. Risk factors span genetic predisposition, psychological distress, lifestyle behaviors, social stressors, and treatment-related variables. A range of interventions-including acupuncture, exercise, psychotherapy, pharmacotherapy, nutritional support, and microbiota modulation-have demonstrated varying degrees of efficacy. We highlight the need for mechanism-specific, personalized interventions and propose directions for future research and clinical practice.