Therapeutic approach to the management of HER2-positive breast cancer metastatic to the brain

Cancer Lett. 2015 Mar 28;358(2):93-99. doi: 10.1016/j.canlet.2014.12.026. Epub 2014 Dec 18.


HER2 positive breast cancers have been shown to have a greater propensity to metastasise to the brain. This may be due to several reasons, including the creation of a "sanctuary-site" for tumour in the brain following trastuzumab therapy. Elucidating the mechanism of this phenomenon may aid the prevention or intervention and treatment of such metastases, but research is limited by the deficiency and diminished access of CNS tissue. However, CNS penetrable HER2 receptor antagonists such as lapatinib and intrathecal administration of trastuzumab might benefit patients, and are worthy of further investigation. New avenues of molecular approach have focused on manipulating signal transduction system involved in HER2 function. The importance of systemic therapies and those targeted to metastatic lesions is emphasised and evaluated here.

Keywords: Brain metastases; Breast cancer; HER2; Signalling pathways.

Publication types

  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Brain Neoplasms / secondary*
  • Brain Neoplasms / therapy*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Disease Management
  • Female
  • Humans
  • Lapatinib
  • Molecular Targeted Therapy
  • Neural Stem Cells / metabolism
  • Neural Stem Cells / transplantation
  • Protein Kinase Inhibitors / pharmacology
  • Protein Kinase Inhibitors / therapeutic use
  • Quinazolines / pharmacology
  • Quinazolines / therapeutic use
  • Radiotherapy
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / genetics*
  • Receptor, ErbB-2 / metabolism
  • Signal Transduction / drug effects
  • Trastuzumab


  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Quinazolines
  • Lapatinib
  • Receptor, ErbB-2
  • Trastuzumab