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Review

Key role of the autonomic nervous system in breast cancer (Review)

  • Authors:
    • Min Wu
    • Zhiwu Zhang
    • Lu Zhou
    • Shiqi Liu
    • Qing Chen
    • Cui Guo
    • Shasha Zhao
    • Xuedan Chen
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, The Third People's Hospital of Honghe Prefecture, Honghe, Yunnan 661400, P.R. China, Department of Geriatrics, Baoshan People's Hospital, Baoshan, Yunnan 678000, P.R. China
  • Article Number: 96
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    Published online on: February 4, 2026
       https://doi.org/10.3892/etm.2026.13091
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Abstract

Evidence from tumor neuroscience and clinical observations have implicated the autonomic nervous system (ANS) in breast cancer pathobiology. Sympathetic activation (norepinephrine/β‑adrenergic signaling) aligns with pro‑angiogenic, pro‑invasive programs and distant spread, whereas increased vagal activity is associated with an anti‑inflammatory state and restraint of progression. The present review summarizes mechanistic, translational and clinical data supporting a bidirectional regulatory model and evaluates a variety of ANS‑targeted strategies, including β‑adrenergic modulation, non‑invasive vagus nerve stimulation and related neuromodulatory approaches. Whilst biologic plausibility is strong, clinical evidence remains heterogeneous and limited by study design. To the best of our knowledge, no adequately powered randomized trials have demonstrated sufficient survival benefits. The present review outlines principles for standardized autonomic phenotyping (such as heart rate variability), candidate patient selection and trial endpoints to test whether ANS modulation can improve recurrence, metastasis, toxicity and quality‑of‑life outcomes. Through integrating convergent evidence and articulating testable hypotheses, the present review provides an ANS‑informed framework to guide future breast cancer research and care.

View Figures

Figure 1

Autonomic imbalance in breast cancer.
Sympathetic overactivation together with reduced vagal tone biases
the tumor microenvironment toward angiogenesis, immune evasion,
invasion and metastasis. Tumor-derived neurotrophic factors (such
as NGF, BDNF and GDNF) can promote tumor-nerve crosstalk and
reinforce this autonomic imbalance, establishing a feed-forward
loop that supports disease progression. By contrast, vagal
(cholinergic) signaling may exert tumor-inhibitory effects, in part
via anti-inflammatory mechanisms and suppression of pro-tumor
immune activation.
View References

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Copy and paste a formatted citation
Spandidos Publications style
Wu M, Zhang Z, Zhou L, Liu S, Chen Q, Guo C, Zhao S and Chen X: <p>Key role of the autonomic nervous system in breast cancer (Review)</p>. Exp Ther Med 31: 96, 2026.
APA
Wu, M., Zhang, Z., Zhou, L., Liu, S., Chen, Q., Guo, C. ... Chen, X. (2026). <p>Key role of the autonomic nervous system in breast cancer (Review)</p>. Experimental and Therapeutic Medicine, 31, 96. https://doi.org/10.3892/etm.2026.13091
MLA
Wu, M., Zhang, Z., Zhou, L., Liu, S., Chen, Q., Guo, C., Zhao, S., Chen, X."<p>Key role of the autonomic nervous system in breast cancer (Review)</p>". Experimental and Therapeutic Medicine 31.4 (2026): 96.
Chicago
Wu, M., Zhang, Z., Zhou, L., Liu, S., Chen, Q., Guo, C., Zhao, S., Chen, X."<p>Key role of the autonomic nervous system in breast cancer (Review)</p>". Experimental and Therapeutic Medicine 31, no. 4 (2026): 96. https://doi.org/10.3892/etm.2026.13091
Copy and paste a formatted citation
x
Spandidos Publications style
Wu M, Zhang Z, Zhou L, Liu S, Chen Q, Guo C, Zhao S and Chen X: <p>Key role of the autonomic nervous system in breast cancer (Review)</p>. Exp Ther Med 31: 96, 2026.
APA
Wu, M., Zhang, Z., Zhou, L., Liu, S., Chen, Q., Guo, C. ... Chen, X. (2026). <p>Key role of the autonomic nervous system in breast cancer (Review)</p>. Experimental and Therapeutic Medicine, 31, 96. https://doi.org/10.3892/etm.2026.13091
MLA
Wu, M., Zhang, Z., Zhou, L., Liu, S., Chen, Q., Guo, C., Zhao, S., Chen, X."<p>Key role of the autonomic nervous system in breast cancer (Review)</p>". Experimental and Therapeutic Medicine 31.4 (2026): 96.
Chicago
Wu, M., Zhang, Z., Zhou, L., Liu, S., Chen, Q., Guo, C., Zhao, S., Chen, X."<p>Key role of the autonomic nervous system in breast cancer (Review)</p>". Experimental and Therapeutic Medicine 31, no. 4 (2026): 96. https://doi.org/10.3892/etm.2026.13091
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