Crosstalk between the peripheral nervous system and breast cancer influences tumor progression

Biochim Biophys Acta Rev Cancer. 2022 Nov;1877(6):188828. doi: 10.1016/j.bbcan.2022.188828. Epub 2022 Oct 22.


Recent studies have shown that peripheral nerves play an important role in the progression of breast cancer. Breast cancer cells (BCCs) promote local peripheral nerve growth and branching by secreting neuroactive molecules, including neurotrophins and axon guidance molecules (AGMs). Sympathetic nerves promote breast cancer progression, while parasympathetic and sensory nerves mainly have anti-tumor effects in the progression of breast cancer. Specifically, peripheral nerves can influence the progression of breast cancer by secreting neurotransmitters not only directly binding to the corresponding receptors of BCCs, but also indirectly acting on immune cells to modulate anti-tumor immunity. In this review, we summarize the crosstalk between breast cancer and peripheral nerves and the roles of important neuroactive molecules in the progression of breast cancer. In addition, we summarize indicators, including nerve fiber density and perineural invasion (PNI), that may help determine the prognosis of breast cancer based on current research results, as well as potential therapeutic approaches, such as β-blockers and retroviral-mediated genetic neuroengineering techniques, that may enhance the prognosis of breast cancer. In addition, we propose suggestions for future research priorities based on a current lack of knowledge in this area.

Keywords: Breast cancer; Innervation; Neuroactive molecule; Perineural invasion; Peripheral nervous system.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Axon Guidance
  • Breast Neoplasms*
  • Female
  • Humans
  • Neoplasm Invasiveness / pathology
  • Peripheral Nervous System / pathology