HER2-positive breast cancer brain metastasis: A new and exciting landscape

Cancer Rep (Hoboken). 2022 Apr;5(4):e1274. doi: 10.1002/cnr2.1274. Epub 2020 Sep 3.


Background: Brain metastases (BrM) incidence is 25% to 50% in women with advanced human epidermal growth factor receptor 2 (HER2)-positive breast cancer. Radiation and surgery are currently the main local treatment approaches for central nervous system (CNS) metastases. Systemic anti-HER2 therapy following a diagnosis of BrM improves outcomes. Previous preclinical data has helped elucidate HER2 brain trophism, the blood-brain/blood-tumor barrier(s), and the brain tumor microenvironment, all of which can lead to development of novel therapeutic options.

Recent findings: Several anti-HER2 agents are currently available and reviewed here, some of which have recently shown promising effects in BrM patients, specifically. New strategies driven by and focusing on brain metastasis-specific genomics, immunotherapy, and preventive strategies have shown promising results and are under development.

Conclusions: The field of HER2+ breast cancer, particularly for BrM, continues to evolve as new therapeutic strategies show promising results in recent clinical trials. Increasing inclusion of patients with BrM in clinical studies, and a focus on assessing their outcomes both intracranially and extracranially, is changing the landscape for patients with HER2+ CNS metastases by demonstrating the ability of newer agents to improve outcomes.

Keywords: CNS involvement; HER2-positive breast cancer; T-DM1; brain metastasis; trastuzumab; tucatinib.

Publication types

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

MeSH terms

  • Brain Neoplasms* / pathology
  • Breast Neoplasms* / drug therapy
  • Female
  • Humans
  • Tumor Microenvironment