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Annals of Oncology Advance Access published online on August 28, 2009
Annals of Oncology, doi:10.1093/annonc/mdp353
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© The Author 2009. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

review

Trastuzumab treatment in patients with breast cancer and metastatic CNS disease

T. Pienkowski1,* and C. C. Zielinski2

1 Department of Breast Cancer and Reconstructive Surgery, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland
2 Clinical Division of Oncology, Department of Medicine I, Medical University Vienna and Central European Cooperative Oncology Group, Vienna, Austria

* Correspondence to: Prof. T. Pienkowski, Department of Breast Cancer and Reconstructive Surgery, Maria Sklodowska-Curie Memorial Cancer Centre and Institute of Oncology, Roentgena 5, 02-781 Warsaw, Poland. Tel: +48-22-644-0024; Fax: +48-22-644-0024; E-mail: tpienkowski{at}coi.waw.pl

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.

breast cancer, metastatic CNS disease, trastuzumab

Received for publication November 20, 2008. Revision received June 9, 2009. Accepted for publication June 12, 2009.


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