脑-瘤轴介导的乳腺癌多模态治疗抵抗:神经内分泌-免疫代谢机制及转化干预OA

Treatment resistance,recurrence,and metastasis of breast cancer remain critical issues affecting long-term patient survival.Chronic psychological stress may act as a host biological driver of breast cancer treatment resistance rather than a mere comorbidity.Through the sustained activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis,also referred to as the"brain-tumor axis",stress signaling reshapes inflammatory,immune,and metabolic networks within the tumor microenvironment and thereby influences chemotherapy,endocrine therapy,anti-HER2 therapy,immunotherapy,and radiotherapy.Current evidence indicates that the key pathways with translational potential are mainly the β-adrenergic axis and the glucocorticoid receptor(GR)pathway.The former is more involved in amplifying inflammatory responses,promoting immunosuppression and metastasis,whereas the latter is closely associated with anti-apoptosis,maintenance of tumor stemness,and reprogramming of estrogen receptor function.This review focuses on the discrepancies in evidence regarding these pathways between population-based studies and preclinical models,and discusses clinically operable non-pharmacologic interventions such as cognitive behavioral stress management,nurse navigation and treatment adherence support,and exercise interventions during the neoadjuvant phase.Although high-level evidence for direct survival benefit remains limited,these interventions have shown favorable effects on cortisol levels,depressive symptoms,quality of life,adherence,relative dose intensity,and some biology-related intermediate endpoints,making them valuable complementary approaches in comprehensive breast cancer management.