Brain-Tumor Axis-Driven Multimodal Therapy Resistance in Breast Cancer: Neuroendocrine-Immunometabolic Mechanisms and Translational Interventions
10.3971/j.issn.1000-8578.2026.26.0006
- VernacularTitle: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
- Author:
Yue WANG
1
;
Die WANG
2
;
Yuanzhi XIANG
2
;
Haihong QIAN
1
Author Information
1. Oncology Center, People’s Hospital of Yuxi, Yuxi 653100, China.
2. Oncology Center, People’s Hospital of Yuxi, Yuxi 653100, China;Graduate School, Clinical College of Dali University, Dali 671003, China.
- Publication Type:REVIEWS
- Keywords:
Breast cancer;
Brain-tumor axis;
Chronic stress;
Treatment resistance;
Non-pharmacologic intervention
- From:
Cancer Research on Prevention and Treatment
2026;53(7):561-565
- CountryChina
- Language:Chinese
-
Abstract:
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.
