Abstract
Human epidermal growth factor receptor (HER)2 over-expression is associated with a shortened disease-free interval and poor survival. Although the addition of trastuzumab to chemotherapy in the first-line setting has improved response rates, progression-free survival, and overall survival, response rates declined when trastuzumab was used beyond the first-line setting because of multiple mechanisms of resistance. Studies have demonstrated the clinical utility of continuing trastuzumab beyond progression, and further trials to explore this concept are ongoing. New tyrosine kinase inhibitors, monoclonal antibodies, PTEN (phosphatase and tensin homolog) pathway regulators, HER2 antibody-drug conjugates, and inhibitors of heat shock protein-90 are being evaluated to determine whether they may have a role to play in treating trastuzumab-resistant metastatic breast cancer.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Adenocarcinoma / chemistry
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Adenocarcinoma / drug therapy
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Adenocarcinoma / genetics
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Adenocarcinoma / secondary*
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Antibodies, Monoclonal / administration & dosage
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Antibodies, Monoclonal / pharmacology
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Antibodies, Monoclonal / therapeutic use
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use*
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Breast Neoplasms / chemistry
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Breast Neoplasms / drug therapy*
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Breast Neoplasms / genetics
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Disease Progression
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Drug Delivery Systems / trends
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Drug Resistance, Neoplasm
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Female
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HSP90 Heat-Shock Proteins / antagonists & inhibitors
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HSP90 Heat-Shock Proteins / physiology
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Humans
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Immunoconjugates / administration & dosage
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Immunoconjugates / therapeutic use
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Insulin-Like Growth Factor I / physiology
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Mucin-4 / physiology
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Neoplasm Proteins / analysis*
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / physiology
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PTEN Phosphohydrolase / physiology
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Protein Kinase Inhibitors / administration & dosage
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Protein Kinase Inhibitors / pharmacology
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Protein Kinase Inhibitors / therapeutic use*
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Randomized Controlled Trials as Topic
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Receptor, ErbB-2 / analysis*
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Receptor, ErbB-2 / chemistry
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Receptor, ErbB-2 / physiology
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Salvage Therapy
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Signal Transduction / drug effects
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Trastuzumab
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Vascular Endothelial Growth Factor A / physiology
Substances
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Antibodies, Monoclonal
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Antibodies, Monoclonal, Humanized
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Antineoplastic Agents
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HSP90 Heat-Shock Proteins
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Immunoconjugates
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MUC4 protein, human
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Mucin-4
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Neoplasm Proteins
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Protein Kinase Inhibitors
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VEGFA protein, human
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Vascular Endothelial Growth Factor A
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Insulin-Like Growth Factor I
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ERBB2 protein, human
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Receptor, ErbB-2
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PTEN Phosphohydrolase
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PTEN protein, human
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Trastuzumab