Beyond trastuzumab: novel therapeutic strategies in HER2-positive metastatic breast cancer

The use of trastuzumab, a monoclonal antibody that targets the human epidermal growth factor receptor 2 (HER2) alteration present in 25 to 30% of breast cancers, has been associated with improved survival outcomes in both the adjuvant and metastatic settings. However, despite the robust clinical eff...

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Bibliographic Details
Published in:British journal of cancer 2012-01, Vol.106 (1), p.6-13
Main Authors: Tsang, R Y, Finn, R S
Format: Article
Language:English
Subjects:
692/699/67/1059/2326
692/699/67/1347
Antibodies, Monoclonal, Humanized - therapeutic use
Antineoplastic Agents - therapeutic use
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Breast cancer
Breast Neoplasms - drug therapy
Breast Neoplasms - metabolism
Cancer Research
Drug Resistance
Epidemiology
Female
Gynecology. Andrology. Obstetrics
Humans
Mammary gland diseases
Medical sciences
mini-review
Minireview
Molecular Medicine
Oncology
Receptor, ErbB-2 - immunology
Receptor, ErbB-2 - metabolism
Trastuzumab
Tumors
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Summary:The use of trastuzumab, a monoclonal antibody that targets the human epidermal growth factor receptor 2 (HER2) alteration present in 25 to 30% of breast cancers, has been associated with improved survival outcomes in both the adjuvant and metastatic settings. However, despite the robust clinical efficacy of trastuzumab in HER2-positive metastatic breast cancer (MBC), primary and secondary resistance remains a clinical challenge. Although lapatinib has demonstrated modest activity in this setting, trials reported to date have yet to demonstrate improvements in overall survival with its use. Novel therapeutic strategies to circumvent trastuzumab resistance are warranted, and agents targeting the HER, vascular endothelial growth factor, heat shock protein 90, phosphoinositide 3 kinase/Akt/mammalian target of rapamycin, and insulin-like growth factor-1 receptor pathways represent rational approaches in the management of HER2-positive disease. In this review, early-phase and emerging trial data surrounding the use of these promising agents in HER2-positive MBC will be discussed.
ISSN:0007-0920
1532-1827
DOI:10.1038/bjc.2011.516