Trastuzumab treatment in patients with breast cancer and metastatic CNS disease

Ann Oncol. 2010 May;21(5):917-24. doi: 10.1093/annonc/mdp353. Epub 2009 Aug 28.

Abstract

Background: Patients with metastatic central nervous system (mCNS) disease progression from breast cancer have a poor prognosis and often develop associated neurological complications. Human epidermal growth factor receptor 2 (HER2)-positivity status increases the risk of developing mCNS disease. Trastuzumab is an mAb that targets HER2 and is known to extend survival across all stages of HER2-positive breast cancer.

Design: This review considers evidence from preclinical and clinical studies examining the value of continuing trastuzumab treatment in patients who develop mCNS disease. A wealth of data from clinical studies showed that trastuzumab prolonged survival in patients with mCNS disease, compared with no trastuzumab treatment, by effectively controlling their non-CNS disease. Trastuzumab has also been shown to penetrate an impaired blood-brain barrier to a limited degree, such as during radiotherapy, and intrathecal delivery of trastuzumab to the central nervous system (CNS) has shown promise. Research efforts are focussing on improving the delivery of trastuzumab to the CNS.

Conclusion: Evidence indicates that patients with mCNS disease from HER2-positive breast cancer should continue to receive trastuzumab to control HER2-positive metastases outside the CNS and receive established therapies to control the mCNS disease.

Publication types

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

MeSH terms

  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Central Nervous System Neoplasms / drug therapy*
  • Central Nervous System Neoplasms / metabolism
  • Central Nervous System Neoplasms / secondary
  • Female
  • Humans
  • Prognosis
  • Receptor, ErbB-2 / metabolism
  • Trastuzumab

Substances

  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Receptor, ErbB-2
  • Trastuzumab