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New challenges and opportunities in the management of brain metastases in patients with ErbB2-positive metastatic breast cancer

Nature Clinical Practice Oncology volume 6, pages 25–33 (2009)Cite this article

Abstract

The introduction of trastuzumab for the treatment of tumors that overexpress ErbB2 (also known as HER2) has contributed significantly to recent improvements in systemic therapy for advanced breast cancer. The advances in systemic therapy have highlighted an increasing prevalence of central nervous system involvement in patients with ErbB2-positive breast cancer and a consequent need for new treatment options for brain metastases. Just as ErbB2-targeted systemic therapy has given rise to this challenge, so too could targeted therapy represent an opportunity to meet it. This Review considers the potential for targeted therapy to facilitate effective management of brain metastases in patients with ErbB2-positive breast cancer, and discusses in particular the data currently available in this setting for lapatinib, an orally available small-molecule tyrosine kinase inhibitor of ErbB1 and ErbB2.

Key Points

  • Improvements in systemic therapy have prolonged survival in patients with breast cancer lesions that overexpress ErbB2, and many patients are now living long enough to develop central nervous system (CNS) disease

  • An association between ErbB2 overexpression and increased risk of developing brain metastases has been reported in both patients with breast cancer treated with trastuzumab and those who did not receive trastuzumab treatment

  • Localized therapies for the treatment of CNS lesions do not manage systemic disease; chemotherapy and biologically targeted therapies are able to treat CNS metastases as well as other sites of systemic disease

  • Continued overexpression of ErbB2 in brain metastases arising from ErbB2-positive breast cancer suggests that if agents could penetrate the blood–brain barrier, ErbB2-targeted therapy could be an effective means of controlling CNS progression

  • Two phase II trials of lapatinib, an orally administered dual tyrosine kinase inhibitor that inhibits ErbB1 and ErbB2, have demonstrated objective responses in breast cancer patients with brain metastases that overexpress ErbB2 and that have progressed after radiation therapy

  • Prophylactic CNS treatment among patients with breast cancer who have a high risk of brain metastases would be reasonable if the agents utilized for prophylaxis were effective, well tolerated, and did not result in considerable long-term complications

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Acknowledgements

The authors thank M Koehler of GlaxoSmithKline for her contribution to the development of the manuscript. ME Melisko and H Rugo receive research funding from GlaxoSmithKline. Writing assistance was provided by Innovex Medical Communications, with funding from GlaxoSmithKline.

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Authors and Affiliations

  1. ME Melisko is a Medical Oncologist and HS Rugo is Clinical Professor of Medicine and Director of the Breast Oncology Clinical Trials Program, both at the University of California, San Francisco Comprehensive Cancer Center, CA,

    Michelle E Melisko & Hope S Rugo

  2. M Glantz is Professor of Oncology and Neurosurgery at the Huntsman Cancer Institute, University of Utah School of Medicine, UT, USA.,

    Michael Glantz

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  1. Michelle E Melisko
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Correspondence to Michelle E Melisko.

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ME Melisko receives research support from GlaxoSmithKline and Schering–Plough. HS Rugo receives research support from GlaxoSmithKline. M Glantz declared no competing interests.

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Melisko, M., Glantz, M. & Rugo, H. New challenges and opportunities in the management of brain metastases in patients with ErbB2-positive metastatic breast cancer. Nat Rev Clin Oncol 6, 25–33 (2009). https://doi.org/10.1038/ncponc1243

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