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The Oncologist, Vol. 8, No. 4, 307–325, August 2003
© 2003 AlphaMed Press

ORIGINAL PAPER
Breast Cancer

The HER-2/neu Gene and Protein in Breast Cancer 2003: Biomarker and Target of Therapy

Jeffrey S. Rossa,b, Jonathan A. Fletcherc, Gerald P. Linetteb,d, James Stecb, Edward Clarkb, Mark Ayersb, W. Fraser Symmanse, Lajos Pusztaie, Kenneth J. Bloomf

a Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York, USA; b Division of Molecular Medicine, Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts, USA; c Department of Pathology, Brigham Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA; d Department of Medicine, Washington University, St. Louis, Missouri, USA; e Departments of Medicine and Pathology, M.D. Anderson Cancer Center, Houston, Texas, USA; f US Labs, Inc., Irvine, California, USA

Correspondence: Jeffrey S. Ross, M.D., Albany Medical College, Department of Pathology, Mail Code 81, 47 New Scotland Avenue, Albany, New York 12208, USA. Telephone: 518-262-5461; Fax: 518-262-8092; e-mail: rossj{at}mail.amc.edu

The HER-2/neu oncogene encodes a transmembrane tyrosine kinase receptor with extensive homology to the epidermal growth factor receptor. In this review, the association of HER-2/neu gene and protein abnormalities with prognosis and response to therapy with trastuzumab and to other therapies in breast cancer is presented. By considering a series of 80 published studies encompassing more than 25,000 patients, the relative advantages and disadvantages of Southern blotting, polymerase chain reaction amplification, and fluorescence in situ hybridization assays designed to detect HER-2/neu gene amplification are compared with HER-2/neu protein overexpression assays performed by immunohistochemical techniques applied to frozen and paraffin-embedded tissues and enzyme immunoassays performed on tumor cytosols. The significance of HER-2/neu overexpression in ductal carcinoma in situ and the HER-2/neu status in uncommon female breast conditions and male breast cancer are also considered. The role of HER-2/neu testing for the prediction of response to trastuzumab therapy in breast cancer is presented as well as its potential impact on responses to standard and newer hormonal therapies, cytotoxic chemotherapy, and radiation. The review also evaluates the status of serum-based testing for circulating HER-2/neu receptor protein and its ability to predict disease outcome and therapy response.

Key Words. Trastuzumab • IHC • FISH • Prognosis • review




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