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Annals of Oncology Advance Access originally published online on January 17, 2007
Annals of Oncology 2007 18(6):977-984; doi:10.1093/annonc/mdl475
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© 2007 European Society for Medical Oncology

reviews

Trastuzumab: mechanism of action, resistance and future perspectives in HER2-overexpressing breast cancer

G Valabrega*,{dagger}, F Montemurro{dagger} and M Aglietta

University Division of Medical Oncology and Haematology, Institute for Cancer Research and Treatment, Strada Provinciale 142, 10060 Candiolo, Torino, Italy

* Correspondence to: Dr G. Valabrega, University Division of Medical Oncology and Haematology, Institute for Cancer Research and Treatment (IRCC). Tel: +39-119933253; Fax: +39-0119933299; E-mail: giorgio.valabrega{at}ircc.it

Trastuzumab is a humanized mAb directed against the extracellular domain of the tyrosine kinase receptor HER2. Trastuzumab has shown clinical activity in HER2-overexpressing breast cancers and, at present, is currently approved for patients whose tumours have this abnormality, in both the metastatic and the adjuvant setting. Several issues about its optimal use, however, are still unresolved. One of the reasons for these uncertainties lies in the absence of conclusive data about its mechanism of action and possible primary or acquired resistance mechanisms. Therefore, clinical questions such as how to optimize patient selection, how to prevent resistance to trastuzumab, or what is the optimal management of those patients whose tumours progress during treatment still await convincing answers. This review summarises the current knowledge on the preclinical and clinical evidence about the mechanism of action of trastuzumab and on the mechanisms underlying the development of resistance and also briefly discusses their possible clinical implications.

Key words: breast neoplasms, HER2, mechanism of action, resistance, trastuzumab

Received for publication May 25, 2006. Revision received September 11, 2006. Accepted for publication November 30, 2006.


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