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Oncologist. 2014 Feb;19(2):135-50. doi: 10.1634/theoncologist.2013-0283. Epub 2014 Jan 16.

Human epidermal growth factor receptor family-targeted therapies in the treatment of HER2-overexpressing breast cancer.

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City of Hope Comprehensive Cancer Center, Duarte, California, USA; Harbor-UCLA Medical Center, Torrance, California, USA.


Breast cancer characterized by overexpression of human epidermal growth factor receptor 2 (HER2) has been associated with more aggressive disease progression and a poorer prognosis. Although an improved understanding of breast cancer pathogenesis and the role of HER2 signaling has resulted in significant survival improvements in the past 20 years, resistance to HER2-targeted therapy remains a concern. A number of strategies to prevent or overcome resistance to HER2-targeted therapy in breast cancer are being evaluated. This article provides a comprehensive review of (a) the role of HER2 signaling in breast cancer pathogenesis, (b) potential receptor and downstream therapeutic targets in breast cancer to overcome resistance to HER2-targeted therapy, and (c) clinical trials evaluating agents targeting one or more members of the HER family and/or downstream pathways for the treatment of breast cancer, with a focus on metastatic disease.


Breast cancer; Epidermal growth factor receptor; Human epidermal growth factor receptor tyrosine kinase receptor family; Tyrosine kinase inhibitor

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