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The complexity of genotypic alterations underlying HER2-positive breast cancer: an explanation for its clinical heterogeneity.

Vanden Bempt I, Drijkoningen M, De Wolf-Peeters C

Department of Pathology, University Hospital of the Katholieke Universiteit Leuven, Leuven, Belgium. isabelle.vandenbempt@uz.kuleuven.ac.be

PURPOSE OF REVIEW: We discuss recent findings on the genotypic alterations associated with HER2-positive breast cancer in an attempt to clarify the clinical heterogeneity observed among these tumors. RECENT FINDINGS: Molecular genetic analysis supports the distinctive nature of HER2-positive breast cancer, which is primarily driven by HER2 gene amplification. Depending on the amplicon size, a variety of genes can be coamplified and overexpressed together with HER2, some of which may contribute to tumorigenesis; the amplicon size may even predict response to trastuzumab therapy. HER2 gene amplification may further destabilize the tumor genome, facilitating the generation of additional genomic aberrations including aneuploidy. The latter might imply polysomy 17, a phenomenon that should be discriminated from true HER2 gene amplification: polysomy 17 in the absence of HER2 gene amplification is not associated with HER2 overexpression nor with the clinical characteristics of HER2-positive breast cancer. SUMMARY: HER2 gene amplification is a complex event: it includes coamplification of other, potentially oncogenic genes and facilitates the generation of additional genomic aberrations. Further studies on these genotypic findings will be helpful to better identify the patients that might benefit from trastuzumab therapy.

Published 1 October 2007 in Curr Opin Oncol, 19(6): 552-7.
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