Abstract
Although trastuzumab-based therapy has changed the treatment paradigm for ErbB2-positive breast cancers, most patients eventually develop progressive disease. Of particular interest is the issue of disease progression in the central nervous system, a safe haven from high molecular weight antibodies like trastuzumab, which have limited ability to cross the blood-brain barrier. This review will discuss therapeutic options for when disease progression has occurred on trastuzumab-based therapies, including central nervous system progression, continuation of trastuzumab-based therapy, addition of novel targeted therapies, and the use of small-molecule tyrosine kinase inhibitors targeting ErbB receptors.
MeSH terms
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Antibodies, Monoclonal / therapeutic use*
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents / therapeutic use*
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / metabolism
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Breast Neoplasms / secondary*
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Clinical Trials as Topic
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Disease Progression
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Drug Resistance, Neoplasm / physiology
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Female
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Humans
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Lapatinib
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Neoplasm Metastasis / drug therapy*
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Protein Kinase Inhibitors / therapeutic use
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Quinazolines / therapeutic use
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Receptor, ErbB-2 / drug effects
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Receptor, ErbB-2 / metabolism*
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Trastuzumab
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents
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Protein Kinase Inhibitors
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Quinazolines
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Lapatinib
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ERBB2 protein, human
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Receptor, ErbB-2
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Trastuzumab