{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:12:06Z","timestamp":1792725126074,"version":"4.5.0"},"reference-count":194,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2003,8,1]],"date-time":"2003-08-01T00:00:00Z","timestamp":1059696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Learning Objectives<\/jats:title>\n                  <jats:p>After completing this course, the reader will be able to:<\/jats:p>\n                  <jats:p>Define the historical background and biological basis of the discovery of the HER-2\/neu gene and its first use as a prognostic factor in breast cancer. Recall the uses of HER-2\/neu testing prior to the approval of trastuzumab including the impact on anthracycline adjuvant and first-line chemotherapy responses. Explain the basic principles of all the HER-2\/neu tests in clinical practice: IHC, FISH, Southern blot, PCR, tissue ELISA, and serum ELISA. Contrast the pros and cons and uses and limitations of the IHC versus the FISH approach to HER-2\/neu testing. Critique the most recent data comparing IHC with FISH for the prediction of response to single-agent trastuzumab and trastuzumab in combination with standard chemotherapy for advanced metastatic breast cancer. Describe the HER-2\/neu expression patterns in all types of breast conditions, including in situ carcinoma, lobular versus ductal carcinoma, Paget's disease, male breast cancer, breast sarcomas, and benign breast disorders.<\/jats:p>\n                  <jats:p>Access and take the CME test online and receive one hour of AMA PRA category 1 credit at CME.TheOncologist.com<\/jats:p>\n                  <jats:p>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.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1634\/theoncologist.8-4-307","type":"journal-article","created":{"date-parts":[[2004,8,24]],"date-time":"2004-08-24T21:38:39Z","timestamp":1093383519000},"page":"307-325","source":"Crossref","is-referenced-by-count":479,"title":["The HER-2\/<i>neu<\/i> Gene and Protein in Breast Cancer 2003: Biomarker and Target of Therapy"],"prefix":"10.1093","volume":"8","author":[{"given":"Jeffrey S.","family":"Ross","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, New York, USA"},{"name":"Division of Molecular Medicine, Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan A.","family":"Fletcher","sequence":"additional","affiliation":[{"name":"Department of Pathology, Brigham Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald P.","family":"Linette","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts, USA"},{"name":"Department of Medicine, Washington University, St. Louis, Missouri, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Stec","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward","family":"Clark","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Ayers","sequence":"additional","affiliation":[{"name":"Division of Molecular Medicine, Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Fraser","family":"Symmans","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pathology, M.D. Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lajos","family":"Pusztai","sequence":"additional","affiliation":[{"name":"Departments of Medicine and Pathology, M.D. Anderson Cancer Center, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth J.","family":"Bloom","sequence":"additional","affiliation":[{"name":"US Labs, Inc., Irvine, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2003,8,1]]},"reference":[{"key":"2021122209331627300_R1","first-page":"1729","article-title":"p185, a product of the neu proto-oncogene, is a receptorlike protein associated with tyrosine kinase activity","volume":"6","author":"Stern","year":"1986","journal-title":"Mol Cell Biol"},{"key":"2021122209331627300_R2","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1002\/j.1460-2075.1996.tb00356.x","article-title":"ErbB-2 is a common auxiliary subunit of NDF and EGF receptors: implications for breast cancer","volume":"15","author":"Karunagaran","year":"1996","journal-title":"EMBO J"},{"key":"2021122209331627300_R3","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1038\/35052073","article-title":"Untangling the ErbB signalling network","volume":"2","author":"Yarden","year":"2001","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2021122209331627300_R4","doi-asserted-by":"crossref","first-page":"5276","DOI":"10.1128\/MCB.16.10.5276","article-title":"A hierarchical network of interreceptor interactions determines signal transduction by Neu differentiation factor\/neuregulin and epidermal growth factor","volume":"16","author":"Tzahar","year":"1996","journal-title":"Mol Cell Biol"},{"key":"2021122209331627300_R5","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1126\/science.3798106","article-title":"Human breast cancer: correlation of relapse and survival with amplification of the Her-2\/neu oncogene","volume":"235","author":"Slamon","year":"1987","journal-title":"Science"},{"key":"2021122209331627300_R6","first-page":"1238","article-title":"Correlation of c-erbB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading","volume":"48","author":"Berger","year":"1988","journal-title":"Cancer Res"},{"key":"2021122209331627300_R7","first-page":"1239","article-title":"Neu-protein overexpression in breast cancer. 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