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a Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York, USA;
b Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA
Key Words. Breast neoplasms • Proto-oncogene c-erbB2 • HER-2/neu • Prognosis • Therapy
Dr. Jeffrey S. Ross, Department of Pathology and Laboratory Medicine, Albany Medical College, Mail Code 81, 47 New Scotland Avenue, Albany, New York 12208, USA.
The HER-2/neu oncogene encodes a transmembrane tyrosine kinase receptor with extensive homology to the epidermal growth factor receptor. HER-2/neu has been widely studied in breast cancer. In this review, the association of HER-2/neu gene and protein abnormalities studied by Southern and slot blotting, immunohistochemistry, enzyme immunoassays, and fluorescence in situ hybridization with prognosis in breast cancer is studied in depth by review of a series of 47 published studies encompassing more than 15,000 patients. The relative advantages of gene amplification assays and frozen/fresh tissue immunohistochemistry over paraffin section immunohistochemistry are discussed. 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 potential value of HER-2/neu status for the prediction of response to therapy in breast cancer is presented in the light of a series of recently published studies showing a range of impact on the outcome of patients treated with hormonal, cytotoxic, and radiation therapies. The evidence that HER-2/neu gene and protein abnormalities in breast cancer predict resistance to tamoxifen therapy and relative sensitivity to chemotherapy regimens including adriamycin is presented. The review will also evaluate the status of serum-based testing for circulating the HER-2/neu receptor protein and its ability to predict disease outcome and therapy response. In the final section, the review will briefly present preliminary data concerning the use of antibody-based therapies directed against the HER-2/neu protein and their potential to become a new modality for breast cancer treatment. The recently presented phase III clinical trial evidence that systemic administration of anti-HER2 antibodies (Herceptin®), alone and in combination with cytotoxic chemotherapy in patients with HER-2/neu overexpressing primary tumors, can increase the time to recurrence and overall response rates in metastatic breast cancer is reviewed.
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|
|
 |
|
 K. Al-Kuraya, P. Schraml, J. Torhorst, C. Tapia, B. Zaharieva, H. Novotny, H. Spichtin, R. Maurer, M. Mirlacher, O. Kochli, et al. Prognostic Relevance of Gene Amplifications and Coamplifications in Breast Cancer Cancer Res., December 1, 2004; 64(23): 8534 - 8540. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
 |
|
 P. S. Bernard and C. T. Wittwer Real-Time PCR Technology for Cancer Diagnostics Clin. Chem., August 1, 2002; 48(8): 1178 - 1185. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
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|
 A. Schneeweiss, M. Hensel, R. Goerner, T. Khbeis, S. Hohaus, G. Egerer, E. Solomayer, R. Haas, E.-M. Grischke, G. Bastert, et al. Comparison of Double and Triple High-Dose Chemotherapy with Autologous Blood Stem Cell Transplantation in Patients with Metastatic Breast Cancer Stem Cells, February 1, 2001; 19(2): 151 - 160. [Abstract] [Full Text]
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|
|
|
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 R. S. Hubert, I. Vivanco, E. Chen, S. Rastegar, K. Leong, S. C. Mitchell, R. Madraswala, Y. Zhou, J. Kuo, A. B. Raitano, et al. STEAP: A prostate-specific cell-surface antigen highly expressed in human prostate tumors PNAS, December 7, 1999; 96(25): 14523 - 14528. [Abstract] [Full Text] [PDF]
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 M. Ferrero-Pous, K. Hacene, M. Tubiana-Hulin, and F. Spyratos Re: Prognostic Importance of Low c-erbB2 Expression in Breast Tumors J Natl Cancer Inst, September 15, 1999; 91(18): 1584 - 1585. [Full Text] [PDF]
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S. Gibson, S. Tu, R. Oyer, S. M. Anderson, and G. L. Johnson Epidermal Growth Factor Protects Epithelial Cells against Fas-induced Apoptosis. REQUIREMENT FOR Akt ACTIVATION J. Biol. Chem., June 18, 1999; 274(25): 17612 - 17618. [Abstract] [Full Text] [PDF]
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