Abstract Purpose of Review Cancer-related fatigue (CRF) is a prevalent and debilitating symptom among breast cancer survivors with a significant adverse impact on quality of life. This comprehensive review synthesizes the current understanding of CRF’s complex pathophysiology, including the interplay of inflammatory, neuroendocrine, and psychosocial mechanisms, and evaluates diverse intervention strategies. Recent Findings Non-pharmacologic approaches (e.g., structured exercise, cognitive-behavioural therapy, mindfulness) have the strongest evidence for alleviating CRF and are emphasized as first-line treatments in oncology guidelines (e.g., ASCO, NCCN, ESMO). In contrast, pharmacologic options such as psychostimulants or bupropion show only modest benefits, with mixed efficacy and notable side effects, underscoring their limited role. Comparing oncology-focused guidelines with those for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) which are psychiatry-focused highlight key differences in management approaches and the need for a unified, multidisciplinary framework across specialtie
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