Neuro-endocrine-immune network mechanisms of non-pharmacological interventions for postoperative depression in breast cancer

Postoperative depression in breast cancer (PDC) is a clinically consequential condition that can adversely affect treatment adherence, functional recovery, symptom burden, and overall quality of life. Emerging evidence indicates that the development and persistence of PDC are driven by dynamic interactions among psychological stress, endocrine dysregulation, autonomic imbalance, and immune-inflammatory activation. Within this context, the neuro-endocrine-immune (NEI) network offers a biologically and clinically informative framework for elucidating both the pathophysiological basis of PDC and the mechanistic underpinnings of non-pharmacological interventions (NPIs). In this mechanism-oriented integrative review, the pathogenesis of PDC is synthesized across three interconnected NEI domains: neural dysregulation, endocrine disturbance, and immune-inflammatory activation. In parallel, the review critically evaluates current evidence for major NPIs, including cognitive behavioral therapy, mindfulness- and acceptance-based approaches, relaxation training, physical exercise, traditional mind–body practices, music- and art-based interventions, acupuncture, and dietary strategies. Available evidence suggests that NPIs may ameliorate depressive symptoms and associated psychological distress through partially convergent mechanisms involving stress appraisal, emotional regulation, sleep and fatigue modulation, hypothalamic–pituitary–adrenal (HPA) axis functioning, autonomic nervous system balance, inflammatory signaling, oxidative stress, and immunometabolic regulation. Nevertheless, the robustness and mechanistic specificity of existing evidence vary considerably across intervention modalities. In general, evidence supporting clinical efficacy exceeds that for direct biological mechanisms, and many hypothesized NEI pathways remain insufficiently validated in populations specifically affected by PDC. Future research should prioritize the integration of clinical outcomes with NEI-related biomarkers and advance symptom- and mechanism-informed intervention models to facilitate more precise and individualized supportive care in breast cancer rehabilitation.