, Volume 21, Issue 2, pp 69–77 | Cite as

HER-2-Positive Breast Cancer

Hope Beyond Trastuzumab
  • Rupert Bartsch
  • Catharina Wenzel
  • Christoph C. Zielinski
  • Guenther G. Steger
Current Opinion


Therapeutic antibodies have shown great promise as targeted agents in the treatment of patients with cancer. Trastuzumab, a humanized monoclonal antibody targeting human epidermal growth factor receptor-2 (HER-2), is of special importance in breast cancers overexpressing HER-2. Such rationally designed substances bind to cancer cells expressing the targeted antigen and, by various mechanisms, lead to tumor cell degradation. Only one-third of patients, however, initially respond to trastuzumab monotherapy and the majority of initial responders demonstrate disease progression within 1 year of treatment initiation. Therefore, alternative compounds targeting the HER-2 receptor or downstream signaling pathways are of great importance.

Lapatinib is a tyrosine kinase inhibitor, blocking tryosine kinase domains of both epidermal growth factor receptor and HER-2. This substance holds promise for the treatment of cancer after trastuzumab failure, and might be active in cerebral metastases. Other strategies in trastuzumab-resistant disease include bispecific antibodies (which bind to HER-2 and Fc receptors, thereby directing immune cells towards the tumor), the combination of antibodies, or targeting tumor vessel growth by blocking vascular endothelial growth factor (VEGF) or VEGF receptors. Heat shock protein 90, a chaperone protein that controls the folding of HER-2, also represents a potential target. Multi-targeted kinase inhibitors such as sunitinib or sortenib are already established in renal cell cancer. These compounds are currently being evaluated in breast cancer and might represent interesting options both in HER-2-positive and -negative disease.

In conclusion, trastuzumab remains the gold standard in HER-2-positive breast cancer therapy. However, in trastuzumab-resistant disease, new strategies and compounds are currently under evaluation.


Breast Cancer Vascular Endothelial Growth Factor Bevacizumab Trastuzumab Brain Metastasis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



The authors have no conflicts of interest that are directly relevant to the content of this review article. No sources of funding were used to assist in the preparation of this review.


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Copyright information

© Adis Data Information BV 2007

Authors and Affiliations

  • Rupert Bartsch
    • 1
  • Catharina Wenzel
    • 1
  • Christoph C. Zielinski
    • 1
  • Guenther G. Steger
    • 1
  1. 1.Department of Medicine 1 and Cancer Center, Clinical Division of OncologyMedical University of ViennaViennaAustria

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