Systemic Therapy for HER2-Positive Central Nervous System Disease: Where We Are and Where Do We Go From Here?

Curr Oncol Rep. 2015 Oct;17(10):46. doi: 10.1007/s11912-015-0471-z.


Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer are at an increased risk of developing brain metastases. The incidence and prevalence of central nervous system (CNS) disease are increasing due to improved survival, which can be attributed to better systemic therapies for extracranial disease. The current standard of care for brain metastases includes a combination of surgery and/or radiation. Systemic therapies are typically reserved for patients with intracranial progression following radiation, due to their limited ability to cross the blood-brain barrier. None of the available anti-HER2 agents (trastuzumab, lapatinib, pertuzumab, and ado-trastuzumab emtansine (T-DM1)) are currently approved for the treatment of brain metastases. Research is underway evaluating novel anti-HER2 agents, which have demonstrated CNS activity. This article discusses the current data on using anti-HER2 therapies to treat CNS disease as well as the newer anti-HER2 agents, which may overcome the current challenges faced in treating brain metastases in the HER2-positive patient population.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal, Humanized / therapeutic use*
  • Blood-Brain Barrier / drug effects*
  • Brain Neoplasms / cerebrospinal fluid
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / secondary
  • Breast Neoplasms / cerebrospinal fluid
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Clinical Trials as Topic
  • Drug Delivery Systems
  • Female
  • Humans
  • Immunoconjugates / therapeutic use
  • Lapatinib
  • Molecular Targeted Therapy*
  • Quinazolines / therapeutic use
  • Receptor, ErbB-2 / cerebrospinal fluid
  • Receptor, ErbB-2 / drug effects*
  • Trastuzumab / therapeutic use


  • Antibodies, Monoclonal, Humanized
  • Immunoconjugates
  • Quinazolines
  • Lapatinib
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • pertuzumab
  • Trastuzumab