Skip to main content
SpringerLink
Log in

HER-2/neu in Breast Cancer: A Possible Means of Therapy?

  • Conference paper
Book cover Symposium in Immunology VII

  • 48 Accesses

Abstract

HER-2/neu (synonyms are erbB-2, c-erbB-2) is a proto-oncogene from the erbB family located on chromosome 17q21 (Smith et al. 1993). This oncogene encodes a 185-kDa transmembrane glycoprotein with an extracellular region which is structurally similar to that of epidermal growth factor receptor and intracellular tyrosine kinase activity (Lupu et al. 1992; Harris et al. 1992). While the extracellular domain has ligand-binding activity (Staebler et al. 1994), the direct natural ligand of HER-2/neu is still unknown (Peles and Yarden 1993).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Allred DC, O’Connell P, Fuqua SA, Osborne CK (1994) Immunohistochemical studies of early breast cancer evolution. Breast Cancer Res Treat 32:13–18

    Article  PubMed  CAS  Google Scholar 

  • Barnes DM, Meyer JS, Gonzalez JG, Gullick WJ, Millis RR (1991) Relationship between c-erbB-2 immunoreactivity and thymidine labelling index in breast carcinoma in situ. Breast Cancer Res Treat 18:11–17

    Article  PubMed  CAS  Google Scholar 

  • Berchuck A, Kamel A, Whitaker R, Kern B, Olt G, Kinney R, Soper JT, Dodge R, Clarke-Pearson DL, Marks P, McKenzie S, Yin S, Bast RC (1990) Overexpression of HER-2/neu is associated with poor survival in advanced epithelial ovarian cancer. Cancer Res 50:4087–4091

    PubMed  CAS  Google Scholar 

  • Frank H, Valone FH, Kaufman PA, Guyre PM, Lewis LD, Memoli V, Deo Y, Graziano R, Fisher JL, Meyer L, Mrozek-Orlowski M, Wardwell K, Guyre V, Morley TL, Arvizu C, Fanger MW (1995) Phase Ia/Ib trial of bispecific antibody MDX-210 in patients with advanced breast or ovarian cancer that overexpresses the protooncogene HER-2/neu. J Clin Oncol 13:2281–2292

    Google Scholar 

  • Gatanaga T, Hwang C, Kohr W (1990) Purification and characterization of an inhibitor (soluble tumor necrosis factor receptor) for tumor necrosis factor and lymphotoxin obtained from the serum ultrafiltrates of human cancer patients. Proc Natl Acad Sci USA 87:8781–8784

    Article  PubMed  CAS  Google Scholar 

  • Gavin JG III, Buell DN, Roth J (1972) Water-soluble insulin receptors from human lymphocytes. Science 178:168–169

    Article  PubMed  CAS  Google Scholar 

  • Harris AL, Nicholson S, Sainsbury R, Wright C, Farndon J (1992) Epidermal growth factor receptor and other oncogenes as prognostic markers. Monogr Natl Cancer Inst 11:181–187

    PubMed  Google Scholar 

  • Harwerth IM, Wels W, Marte BM, Hynes NE (1992) Monoclonal antibodies against the extracellular domain of the erbB-2 receptor function as partial ligand agonists. J Biol Chem 267:15160–15167

    PubMed  CAS  Google Scholar 

  • Harwerth IM, Wels W, Schlegel J, Muller M, Hynes NE (1993) Monoclonal antibodies directed to the erbB-2 receptor inhibit in vivo tumour cell growth. Br J Cancer 68:1140–1145

    Article  PubMed  CAS  Google Scholar 

  • Horiguchi J, Lino Y, Takei H, Yokoe T, Ishida T, Morishita Y (1994) Immunohistochemical study on the expression of c-erbB-2 oncoprotein in breast cancer. Oncology 51: 47–51

    Article  PubMed  CAS  Google Scholar 

  • Hurwitz E, Stancovski I, Sela M, Yarden Y (1995) Suppression and promotion of tumor growth by monoclonal antibodies to erbB-2 differentially correlate with cellular uptake. Proc Natl Acad Sci USA 92:3353–3357

    Article  PubMed  CAS  Google Scholar 

  • Isola J J, Holli K, Oksa H, Teramoto Y, Kallioniemi OP (1994) Elevated erbB-2 oncoprotein levels in preoperative and follow-up serum samples define an aggressive disease course in patients with breast cancer. Cancer 73:652–658

    Article  PubMed  CAS  Google Scholar 

  • Kallioniemi OP, Holli K, Visakorpi T, Koivula T, Helin HH, Isola JJ (1991) Association of c-erbB-2 protein over-expression with high rate of cell proliferation, increased risk of visceral metastasis and poor long-term survival in breast cancer. Int J Cancer 49:650–655

    Article  PubMed  CAS  Google Scholar 

  • Kandl H, Seymour L, Bezwoda WR (1994) Soluble c-erbB-2 fragment in serum correlates with disease stage and predicts for shortened survival in patients with earlystage and advanced breast cancer. Br J Cancer 70:739–742

    Article  PubMed  CAS  Google Scholar 

  • Kasprzyk PG, Song SU, Di Fiore PP, King CR (1992) Therapy of an animal model of human gastric cancer using a combination of anti-erbB-2 monoclonal antibodies. Cancer Res 52:2771–2776

    PubMed  CAS  Google Scholar 

  • Kern JA, Schwartz DA, Nordberg JE, Weiner DB, Greene MI, Torney L, Robinson RA (1990) p185neu expression in human lung adenocarcinomas predicts shortened survival. Cancer Res 50:5184–5191

    PubMed  CAS  Google Scholar 

  • Kynast B, Binder L, Marx D, Zoll B, Schmoll HJ, Oellerich M, Schauer A (1993) Determination of a fragment of the c-erbB-2 translational product pi85 in serum of breast cancer patients. J Cancer Res Clin Oncol 119:249–252

    Article  PubMed  CAS  Google Scholar 

  • Leitzel K, Teramoto Y, Sampson E, Mauceri J, Langton BC, Demers L, Podczaski E, Harvey H, Shambaugh S, Volas G, Weaver S, Lipton A (1992) Elevated soluble c-erbB-2 antigen levels in the serum and effusions of a proportion of breast cancer patients. J Clin Oncol 10:1436–1443

    PubMed  CAS  Google Scholar 

  • Lewis GD, Figari I, Fendly B, Wong WL, Carter P, Gorman C, Shepard HM (1993) Differential responses of human tumor cell lines to anti-p185HER2 monoclonal antibodies. Cancer Immunol Immunother 37:255–263

    Article  PubMed  CAS  Google Scholar 

  • Lupu R, Colomer R, Kannan B, Lippman ME (1992) Characterization of a growth factor that binds exclusively to the erbB-2 receptor and induces cellular responses. Proc Natl Acad Sci USA 89:2287–2291

    Article  PubMed  CAS  Google Scholar 

  • Muss HB, Thor AD, Berry DA, Kute T, Liu ET, Koerner F, Cirrincione CT, Budman DR, Wood WC, Barcos M, Henderson IC (1994) c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med 330:1260–1266

    Article  PubMed  CAS  Google Scholar 

  • Narita T, Funahashi H, Satoh Y, Takagi H (1993) c-erbB-2 protein in the sera of breast cancer patients. Breast Cancer Res Treat 24:97–102

    Article  Google Scholar 

  • O’Reilly SM, Barnes DM, Camplejohn RS, Bartkova J, Gregory WM, Richards MA (1991) The relationship between c-erbB-2 expression, S-phase fraction and prognosis in breast cancer. Br J Cancer 63:444–446

    Article  PubMed  Google Scholar 

  • Paik S, Hazan R, Fisher ER, Sass RE, Fisher B, Redmond C, Schlessinger J, Lippman ME, King CR (1990) Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein overexpression in primary breast cancer. J Clin Oncol 8:103–112

    PubMed  CAS  Google Scholar 

  • Park JW, Hong K, Carter P, Asgari H, Guo LY, Keller GA, Wirth C, Shalaby R, Kotts C, Wood WI, Papahadjopoulos D, Benz CC (1995) Development of anti-pi85HER2 immunoliposomes for cancer therapy. Proc Natl Acad Sci USA 92:1327–1331

    Article  PubMed  CAS  Google Scholar 

  • Peles E, Yarden Y (1993) Neu and its ligands: from an oncogene to neural factors. Bioessays 15:815–824

    Article  PubMed  CAS  Google Scholar 

  • Press MF, Hung G, Godolphin W, Slamon DJ (1994) Sensitivity of HER-2/neu antibodies in archival tissue samples: potential source of error in immunohistochemical studies of oncogene expression. Cancer Res 54:2771–2777

    PubMed  CAS  Google Scholar 

  • Pupa SM, Menard S, Morelli D, Pozzi B, De Palo G, Colnaghi MI (1993a) The extracellular domain of the c-erbB-2 oncoprotein is released from tumor cells by proteolytic cleavage. Oncogene 8:2917–2923

    PubMed  CAS  Google Scholar 

  • Pupa SM, Menard S, Andreola S, Colnaghi MI (1993b) Antibody response against the c-erbB-2 oncoprotein in breast carcinoma patients. Cancer Res 53:5864–5866

    PubMed  CAS  Google Scholar 

  • Rubin LA, Jay G, Nelson DL (1986) The released interleukin-2 receptor binds interleukin-2 efficiently. J Immunol 137:3841–3845

    PubMed  CAS  Google Scholar 

  • Schonborn I, Zschiesche W, Spitzer E, Minguillon C, Mohner M, Ebeling K, Grosse R (1994) c-erbB-2 overexpression in primary breast cancer: independent prognostic factor in patients at high risk. Breast Cancer Res Treat 29:287–295

    Google Scholar 

  • Seshadri R, Firgaira FA, Horsfall DJ, McKaul K, Setlur V, Kitchen B (1993) Clinical significance of HER-2/neu oncogene amplification in primary breast cancer. The South Australian Breast Cancer Study Group. J Clin Oncol 11:1936–1942

    PubMed  CAS  Google Scholar 

  • Slamon DJ, Clark GM, Wong SG, Levin WJ, Ullrich A, McGuire WL (1987) Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene. Science 23:177–182

    Article  Google Scholar 

  • Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A, Press MF (1989) Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244:707–712

    Article  PubMed  CAS  Google Scholar 

  • Smith K, Houlbrook S, Greenall M, Carmichael J, Harris AL (1993) Topoisomerase Ila co-amplification with erbB-2 in human primary breast cancer and breast cancer cell lines: relationship to m-AMSA and mitoxantrone sensitivity. Oncogene 8:933–938

    PubMed  CAS  Google Scholar 

  • Staebler A, Sommers C, Mueller SC, Byers S, Thompson EW, Lupu R (1994) Modulation of breast cancer progression and differentiation by the gp3o/heregulin. Breast Cancer Res Treat 31:175–182

    Article  PubMed  CAS  Google Scholar 

  • Stancovski I, Hurwitz E, Leitner O, Ullrich A, Yarden Y, Sela M (1991) Mechanistic aspects of the opposing effects of monoclonal antibodies to the erbB-2 receptor on tumor growth. Proc Natl Acad Sci USA 88:8691–8695

    Article  PubMed  CAS  Google Scholar 

  • Tandon AK, Clark GM, Chamness GC, Ullrich A, McGuire WL (1989) HER-2/neu oncogene protein and prognosis in breast cancer. J Clin Oncol 7:1120–1128

    PubMed  CAS  Google Scholar 

  • Toikkanen S, Helin H, Isola J, Joensuu H (1992) Prognostic significance of HER-2 oncoprotein expression in breast cancer: a 30-year follow up. J Clin Oncol 10:1044–1048

    PubMed  CAS  Google Scholar 

  • Tsai CM, Chang KT, Perng RP, Mitsudomi T, Chen MH, Kadoyama C, Gazdar AF (1993) Correlation of intrinsic chemoresistance of non-small-cell lung cancer cell lines with HER-2/neu gene expression but not with ras gene mutations. J Natl Cancer Inst 85:897–901

    Article  PubMed  CAS  Google Scholar 

  • Weber W, Gill GN, Spiess J (1984) Production of an epidermal growth factor receptor-related protein. Science 224:294–297

    Article  PubMed  CAS  Google Scholar 

  • Wiltschke C, Krainer M, Budinsky A, Berger A, Miiller C, Zeillinger R, Speiser P, Kubista E, Eibl M, Zielinski CC (1995) Reduced mitogenic stimulation of peripheral blood mononuclear cells as a prognostic parameter for the course of breast cancer: a prospective longitudinal study. Br J Cancer 71:1292–1296

    Article  PubMed  CAS  Google Scholar 

  • Wu JT, Astill ME, Zhang P (1993) Detection of the extracellular domain of c-erbB-2 oncoprotein in sera from patients with various carcinomas: correlation with tumor markers. I Clin Lab Anal 7:31–40

    Article  CAS  Google Scholar 

  • Zeillinger R, Schneeberger C, Speiser P (1993) Rapid quantitative analysis of differential PCR products by high-performance liquid chromatography. Biotechniques 15:89–95

    PubMed  CAS  Google Scholar 

Download references

Authors
  1. T. Brodowicz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Wiltschke
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. C. Zielinski
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Institut für Immunologie der Universität Wien, Borschkegasse 8 a, 1090, Wien, Austria

    Martha M. Eibl

  2. Abteilung Hämatologie, Johannes Gutenberg Universität, Langenbeckstr. 1, 55101, Mainz, Germany

    Christoph Huber

  3. Abteilung für Rheumatologie und Klinische Immunologie, Medizinische Universitätsklinik, Hugstetter Str. 55, 79106, Freiburg, Germany

    Hans H. Peter

  4. Pädiatrische Pneumologie und Immunologie, Universitäts-Klinikum Rudolf-Virchow Standort Charlottenburg, Heubnerweg 6, 14059, Berlin, Germany

    Ulrich Wahn

Rights and permissions

Reprints and permissions

Copyright information

© 1998 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Brodowicz, T., Wiltschke, C., Zielinski, C.C. (1998). HER-2/neu in Breast Cancer: A Possible Means of Therapy?. In: Eibl, M.M., Huber, C., Peter, H.H., Wahn, U. (eds) Symposium in Immunology VII. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-80466-3_11

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-80466-3_11

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-63360-0

  • Online ISBN: 978-3-642-80466-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation