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International Journal of Breast Cancer
Volume 2011 (2011), Article ID 352182, 11 pages
Review Article

Molecular Mechanisms of Trastuzumab Resistance in HER2 Overexpressing Breast Cancer

Immunobiology Department, Institute of Oncology A. H. Roffo, University of Buenos Aires, Avenida San Martín 5481, CP1417 DTB Buenos Aires, Argentina

Received 30 April 2011; Accepted 1 July 2011

Academic Editor: Alejandro J. Urtreger

Copyright © 2011 Gabriel L. Fiszman and María A. Jasnis. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


The epidermal growth factor receptor 2 (HER2) is a tyrosine kinase overexpressed in nearly 20% to 25% of invasive breast cancers. Trastuzumab is a humanized monoclonal antibody that targets HER2. The majority of patients with metastatic breast cancer initially respond to trastuzumab, however, within 1 year of treatment disease progresses. Several molecular mechanisms have been described as contributing to the development of trastuzumab resistance. They could be grouped as impaired access of trastuzumab to HER2, upregulation of HER2 downstream signaling pathways, signaling of alternative pathways, and impaired immune antitumor mechanisms. However, since many of them have overlapping effects, it would be of great clinical impact to identify the principal signaling pathways involved in drug resistance. Significant efforts are being applied to find other therapeutic modalities besides trastuzumab treatment to be used alone or in combination with current modalities.