← Back to Search
HER-2/neu Oncogene Protein And Prognosis In Breast Cancer.
A. K. Tandon, G. Clark, G. Chamness, A. Ullrich, W. Mcguire
Published 1989 · Medicine
Download PDFAnalyze on Scholarcy
Amplification of the HER-2/neu oncogene was recently reported to predict poor clinical outcome in node-positive breast cancer patients. Since expression of the oncogene as its protein product might be even more closely related than gene amplification to disease progression, we have now examined levels of the HER-2/neu oncogene protein for its prognostic potential in both node-positive and node-negative breast cancer. Using Western blot analysis, levels of this protein were determined in 728 primary human breast tumor specimens. We examined relationships between this protein and other established markers of prognosis, as well as clinical outcome. In node-negative patients (n = 378), the HER-2/neu protein failed to predict disease outcome. However, in node-positive patients (n = 350), those patients with higher HER-2/neu protein had statistically shorter disease-free (P = .0014) and overall survival (P less than .0001) than patients with lower levels of the protein. Higher HER-2/neu protein was found in tumors without estrogen receptor (ER) (P = .02) or progesterone receptor (PgR) (P = .0003), and in patients with more than three positive lymph nodes (P = .04). A significant correlation between levels of the HER-2/neu gene protein and amplification of the gene itself was also found (n = 48, P less than .001). Multivariate analyses in these patients showed that the HER-2/neu protein is a significant independent predictor of both the disease-free and the overall survival in node-positive breast cancer, even when other prognostic factors are considered.
This paper references
DNA flow cytometry and prognostic factors in 1331 frozen breast cancer specimens
L. Dressler (1988)
OVEREXPRESSION OF THE c-erbB-2 ONCOPROTEIN IN HUMAN BREAST CARCINOMAS: IMMUNOHISTOLOGICAL ASSESSMENT CORRELATES WITH GENE AMPLIFICATION
DeonJ. Venter (1987)
Antibodies to the autophosphorylation sites of the epidermal growth factor receptor protein‐tyrosine kinase as probes of structure and function.
W. Gullick (1985)
Measurement of protein using bicinchoninic acid.
P. Smith (1985)
Regression Models and Life-Tables
D. Cox (1972)
Association of multiple copies of the c-erbB-2 oncogene with spread of breast cancer.
D. Zhou (1987)
Neu-protein overexpression in breast cancer. Association with comedo-type ductal carcinoma in situ and limited prognostic value in stage II breast cancer.
M. J. van de Vijver (1988)
Evaluation of survival data and two new rank order statistics arising in its consideration.
N. Mantel (1966)
Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications.
H. Towbin (1979)
Transposition and amplification of oncogene-related sequences in human neuroblastomas
N. Kohl (1983)
Monoclonal antibodies reactive with distinct domains of the neu oncogene-encoded p185 molecule exert synergistic anti-tumor effects in vivo.
J. Drebin (1988)
EPIDERMAL-GROWTH-FACTOR RECEPTOR STATUS AS PREDICTOR OF EARLY RECURRENCE OF AND DEATH FROM BREAST CANCER
J. Richard (1987)
Analysis of Survival Data under the Proportional Hazards Model
N. Breslow (1975)
Immunohistochemical detection of the neu protein in tissue sections of human breast tumors with amplified neu DNA.
M. J. van de Vijver (1988)
Amplification of a novel v-erbB-related gene in a human mammary carcinoma.
C. R. King (1985)
Amplification, enhanced expression and possible rearrangement of EGF receptor gene in primary human brain tumours of glial origin
T. Libermann (1985)
Amplification of N-myc in untreated human neuroblastomas correlates with advanced disease stage.
G. Brodeur (1984)
The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity.
T. Akiyama (1986)
Multiple independent activations of the neu oncogene by a point mutation altering the transmembrane domain of p185
C. Bargmann (1986)
Immunohistochemical localization of c-erbB-2 in human breast carcinomas.
B. Gusterson (1987)
Genetic alteration of the c-myc protooncogene (MYC) in human primary breast carcinomas.
C. Escot (1986)
Measurement of progesterone receptor in human breast cancer biopsies.
B. Powell (1979)
Proto-oncogene abnormalities in human breast cancer: correlations with anatomic features and clinical course of disease.
M. Cline (1987)
A v-erbB-related protooncogene, c-erbB-2, is distinct from the c-erbB-1/epidermal growth factor-receptor gene and is amplified in a human salivary gland adenocarcinoma.
K. Semba (1985)
Progesterone receptors as a prognostic factor in stage II breast cancer.
G. Clark (1984)
Evaluation of estrogen receptor assays in human breast cancer tissue.
Mcguire Wl (1977)
Alterations to either c-erbB-2(neu) or c-myc proto-oncogenes in breast carcinomas correlate with poor short-term prognosis.
J. Varley (1987)
Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene.
L. Coussens (1985)
Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.
D. Slamon (1987)
Correlation of c-erbB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading.
M. Berger (1988)
Sporadic amplification of the HER2/neu protooncogene in adenocarcinomas of various tissues.
M. Tal (1988)
Amplification of c-erbB-2 and aggressive human breast tumors?
D. Slamon (1988)
AMPLIFICATION OF c-erbB-2 ONCOGENE IN HUMAN ADENOCARCINOMAS IN VIVO
J. Yokota (1986)
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
U. Laemmli (1970)
Increased expression of the putative growth factor receptor p185HER2 causes transformation and tumorigenesis of NIH 3T3 cells.
R. Hudziak (1987)
The molecular genetics of cancer.
J. Bishop (1987)
The molecular genetics of cellular oncogenes.
H. Varmus (1984)
Genetic alterations of the c-erbB-2 oncogene occur frequently in tubular adenocarcinoma of the stomach and are often accompanied by amplification of the v-erbA homologue.
J. Yokota (1988)
Prediction of relapse or survival in patients with node-negative breast cancer by DNA flow cytometry.
G. Clark (1989)
Elevated ras oncogene expression correlates with lymph node metastases in breast cancer patients.
J. Lundy (1986)
Survival from first recurrence: relative importance of prognostic factors in 1,015 breast cancer patients.
G. Clark (1987)
Amplification of the neu (c-erbB-2) oncogene in human mammmary tumors is relatively frequent and is often accompanied by amplification of the linked c-erbA oncogene.
M. van de Vijver (1987)
Association of multiple copies of the N-myc oncogene with rapid progression of neuroblastomas.
R. Seeger (1985)
The Statistical Analysis of Failure Time Data
J. D. Kalbfleisch (1980)
This paper is referenced by
Breast cancer subtypes and survival in Chinese women with operable primary breast cancer
Zhao-sheng Li (2011)
β4 integrin subunit gene expression correlates with tumor size and nuclear grade in early breast cancer
L. K. Diaz (2005)
Tissue microarrays for rapid linking of molecular changes to clinical endpoints.
J. Torhorst (2001)
c-erbB2 expression in different histological types of invasive breast carcinoma
S. Soomro ()
Quantitative Assessment of HER-2/Neu Protein Concentration in Breast Cancer by Enzyme-Linked Immunosorbent Assay
V. Müller (2003)
Influence of circulating c-erbB-2 serum protein on response to adjuvant chemotherapy in node-positive breast cancer patients
T. Fehm (2004)
The small heat shock protein HSP27 is not an independent prognostic marker in axillary lymph node-negative breast cancer patients.
S. Oesterreich (1996)
The prognostic value of c-erbB2 in primary breast carcinomas: A study on 942 cases
N. Quénel (2004)
Monoclonal antibodies as agonists: an expanded role for their use in cancer therapy.
E. Vitetta (1994)
Prognostic significance of c-erb B-2 protein status using an enzyme immunoassay in breast cancer
E. Shin (2000)
Therapy of small breast cancer: a prospective study on 1036 patients with special emphasis on prognostic factors.
R. Sauer (1992)
Molecular biology of breast cancer.
N. Lemoine (1994)
Elevated serum levels of a c-erbB-2 oncogene product in ovarian cancer patients and in pregnancy
H. Meden (2005)
Growth factors and oncogenes in human solid tumors: clinical aspects.
J. Bonneterre (1990)
Proliferating cell nuclear antigen in breast lesions: Correlation of c-erbB-2 oncoprotein and EGF receptor and its clinicopathological significance in breast cancer
P. Shrestha (2005)
Structure-Based and Ligand-Based Drug Design for HER 2 Receptor
Hung-Jin Huang (2010)
Soluble ectodomain of c-erbB-2 oncoprotein in relation to tumour stage and grade in human renal cell carcinoma.
T. Rasmuson (1997)
Aneuploidy in breast cancer: a fluorescence in situ hybridization study.
S. Shackney (1995)
Sensitivity of HER-2/neu antibodies in archival tissue samples: potential source of error in immunohistochemical studies of oncogene expression.
M. Press (1994)
PathVysionTM HER-2 DNA Probe Kit (LSI® HER-2/neu SpectrumOrangeTM / CEP® 17 SpectrumGreenTM)
Her-2/neu Overexpression Due to Polysomy 17 in Breast Cancer: Molecular Testing to Guide Therapeutic Options
R. Sahoo (2011)
Follow-up Study of HER-2 / neu Amplification in Primary Breast Cancer 1
Gary M. Clark (2006)
c-erbB-2 protein overexpression in breast cancer is a risk factor in patients with involved and uninvolved lymph nodes.
W. Gullick (1991)
Analysis of naïve and memory CD4 and CD8 T cell populations in breast cancer patients receiving a HER2/neu peptide (E75) and GM-CSF vaccine
M. Hueman (2006)
Estrogen receptor-positive, progesterone receptor-negative breast cancer: association with growth factor receptor expression and tamoxifen resistance.
G. Arpino (2005)
Quantum leaps in treatment of high-risk breast cancer? Prove it!
V. Jones (1993)
The type I growth factor receptors in human breast cancer
T. Rajkumar (2004)
Identification and Role of the MTA1 Complex in Small Intestinal Carcinoids Malignancy
M. Zikusoka (2006)
Immunohistochemical detection of HER2/neu in patients with axillary lymph node negative breast carcinoma. A study of epidemiologic risk factors, histologic features, and prognosis
P. Rosen (1995)
Molecular Testing in Breast Cancer
D. Zardavas (2014)
HER-2 status in gastrointestinal stromal tumor.
L. F. Lopes (2008)
Clinicopathologic Significance of the Intratumoral Heterogeneity of HER2 Gene Amplification in HER2-Positive Breast Cancer Patients Treated With Adjuvant Trastuzumab.
H. Lee (2015)See more