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Annals of Oncology 2005 16(Supplement 4):iv7-iv13; doi:10.1093/annonc/mdi901
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© 2005 European Society for Medical Oncology

Invited Paper

Targeting HER2 as a therapeutic strategy for breast cancer: a paradigmatic shift of drug development in oncology

M. De Laurentiis1, G. Cancello1, L. Zinno1, E. Montagna1, L. Malorni1, A. Esposito1, R. Pennacchio1, L. Silvestro1, M. Giuliano1, A. Giordano1, F. Caputo1, A. Accurso2 and S. De Placido1,*

1 Dept. of Endocrinology and Molecular and Clinical Oncology; 2 Dept. of General and Geriatric Surgery and Digestive and Operative Endoscopy, University Federico II, Napoli, Italy

* Correspondence to: Dr Sabino De Placido, Professor of Oncology, Dept. Endocrinology and Molecular and Clinical Oncology, Università Federico II, Via S. Pansini 5, 80131 Napoli, Italy. Tel: +39-081–7464286; Fax: +39-081–2290150; Email: deplacid{at}unina.it

Targeted therapies are causing a dramatic change in cancer drug development. Trastuzumab, a humanised recombinant monoclonal antibody that recognizes the extracellular domain of HER2 trans-membrane protein, is among the first target-specific drugs that have been licensed for clinical use and its development represents a model of integration of new agents with classical treatment strategies. In preclinical models, trastuzumab has demonstrated a marked antiproliferative effect and a synergistic action with several chemotherapeutic agents. Monotherapy trials indicate that trastuzumab is active as a single agent in HER2 positive patients, is well tolerated, and is associated with preservation of quality of life (QoL). Furthermore, as first line therapy for metastatic breast cancer overexpressing HER2 receptor, the addition of trastuzumab to taxane-based chemotherapy significantly increased rate of objective response, time to disease progression and survival when compared with chemotherapy alone. Trastuzumab has shown important activity when used with many chemotherapeutic agents such as platinum salts, gemcitabine, vinorelbine and capecitabine and liposomal anthracyclines. Various trials are now ongoing to optimize the use of trastuzumab and to investigate its role in the adjuvant and in the neo-adjuvant setting.

Key words: HER2, breast cancer, targeted therapy, trastuzumab


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