Molecular and cellular mechanisms underlying brain metastasis of breast cancer

Cancer Metastasis Rev. 2020 Sep;39(3):711-720. doi: 10.1007/s10555-020-09881-y.


Metastasis of cancer cells to the brain occurs frequently in patients with certain subtypes of breast cancer. In particular, patients with HER2-positive or triple-negative breast cancer are at high risk for the development of brain metastases. Despite recent advances in the treatment of primary breast tumors, the prognosis of breast cancer patients with brain metastases remains poor. A better understanding of the molecular and cellular mechanisms underlying brain metastasis might be expected to lead to improvements in the overall survival rate for these patients. Recent studies have revealed complex interactions between metastatic cancer cells and their microenvironment in the brain. Such interactions result in the activation of various signaling pathways related to metastasis in both cancer cells and cells of the microenvironment including astrocytes and microglia. In this review, we focus on such interactions and on their role both in the metastatic process and as potential targets for therapeutic intervention.

Keywords: Astrocyte; Brain metastasis; Breast cancer; PI3K-Akt; STAT3; xCT.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain Neoplasms / drug therapy
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / secondary*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Female
  • Humans
  • Molecular Targeted Therapy
  • Receptor, ErbB-2 / metabolism
  • Signal Transduction
  • Triple Negative Breast Neoplasms / drug therapy
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology
  • Tumor Microenvironment


  • Receptor, ErbB-2