Online citations, reference lists, and bibliographies.
Please confirm you are human
(Sign Up for free to never see this)
← Back to Search

HER-2/neu In Node-negative Breast Cancer: Prognostic Significance Of Overexpression Influenced By The Presence Of In Situ Carcinoma.

D. Allred, G. Clark, A. K. Tandon, R. Molina, D. Tormey, C. Osborne, K. Gilchrist, E. Mansour, M. Abeloff, L. Eudey
Published 1992 · Medicine

Save to my Library
Download PDF
Analyze on Scholarcy
PURPOSE Amplification and/or overexpression of the HER-2/neu oncogene have been shown to correlate with poor clinical outcome in patients with axillary node-positive breast cancer. In contrast, the prognostic significance of HER-2/neu in node-negative disease is controversial. This study was undertaken to evaluate further the relationship between HER-2/neu and clinical outcome in node-negative disease. PATIENTS AND METHODS Overexpression of HER-2/neu was evaluated by permanent-section immunohistochemistry in tumors from 613 patients with long-term clinical follow-up enrolled in the Intergroup Study 0011. Patients were stratified into low-risk (n = 307) and high-risk (n = 306) groups on the basis of tumor size and estrogen-receptor (ER) status. Low-risk patients were defined as having small (less than 3 cm), ER-positive tumors and were observed without additional treatment after initial surgery. High-risk patients had either ER-negative or large (greater than or equal to 3 cm), ER-positive tumors and were randomized to be observed (n = 146) or to receive adjuvant chemotherapy (n = 160) after surgery. RESULTS The rate of HER-2/neu overexpression was 14.3% in all tumors combined and was higher in invasive carcinomas with (21.5%) than without (11.2%) a significant noninvasive or in situ histologic component (P less than .0001). There was no relationship between overexpression and clinical outcome in the natural history setting of combined low-risk and high-risk patients not receiving adjuvant therapy (n = 453). Based on the reasoning that the influence of HER-2/neu may have been obscured by high-risk features and/or the presence of noninvasive carcinoma, we also analyzed the subset of patients with low-risk lesions not containing a significant in situ component (n = 179). Patients of this group with HER-2/neu-positive tumors showed only 40% disease-free survival (DFS) at 5 years, compared with over 80% in patients with HER-2/neu-negative tumors (P less than .0001). A similar inverse correlation was observed between overexpression and overall survival in the same group of patients (P = .0001). In a separate analysis involving patients receiving adjuvant chemotherapy, those with HER-2/neu-negative tumors showed significantly improved DFS in response to therapy compared with patients with HER-2/neu-positive tumors. CONCLUSION Overexpression of HER-2/neu is associated with poor clinical outcome in a subset of node-negative patients with small, ER-positive, predominantly invasive tumors and may play a role in resistance to adjuvant chemotherapy.
This paper references
Amplification of c-erbB-2 and aggressive human breast tumors?
D. Slamon (1988)
Proto-oncogene abnormalities in human breast cancer: c-ERBB-2 amplification does not correlate with recurrence of disease.
D. Zhou (1989)
Alterations to either c-erbB-2(neu) or c-myc proto-oncogenes in breast carcinomas correlate with poor short-term prognosis.
J. Varley (1987)
Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.
D. Slamon (1987)
c-erbB-2 protein expression in node negative breast cancer.
J. Richner (1990)
Evaluation of survival data and two new rank order statistics arising in its consideration.
N. Mantel (1966)
c-erbB-2 protein overexpression in breast cancer is a risk factor in patients with involved and uninvolved lymph nodes.
W. Gullick (1991)
An immunohistochemical evaluation of c-erbB-2 expression in human breast carcinoma.
D. Barnes (1988)
An evaluation of immunoreactivity for c-erbB-2 protein as a marker of poor short-term prognosis in breast cancer.
R. Walker (1989)
HER-2/neu oncogene expression and proliferation in breast cancers.
S. Bacus (1990)
Expression of c-erbB-2 oncoprotein: a prognostic indicator in human breast cancer.
C. Wright (1989)
Analysis of c-erbB-2 expression in breast carcinomas with clinical follow-up.
A. Thor (1989)
c-erbB-2 amplification in node-negative human breast cancer.
J. Ro (1989)
Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene.
L. Coussens (1985)
Amplification and protein over-expression of the neu/HER-2/c-erbB-2 protooncogene in human breast carcinomas: relationship to loss of gene sequences on chromosome 17, family history and prognosis.
A. Børresen (1990)
Expression of HER-2/neu oncoprotein in human breast cancer: a comparison of immunohistochemical and western blot techniques.
R. Molina (1992)
Long‐term survival in breast cancer related to overexpression of the c‐erbB‐2 oncoprotein: An immunohistochemical study using monoclonal antibody NCL‐CB11
R. Dykins (1991)
A randomized clinical trial evaluating sequential methotrexate and fluorouracil in the treatment of patients with node-negative breast cancer who have estrogen-receptor-negative tumors.
B. Fisher (1989)
Association of multiple copies of the c-erbB-2 oncogene with spread of breast cancer.
D. Zhou (1987)
Nonparametric Estimation from Incomplete Observations
E. L. Kaplan (1958)
Correlation between long-term survival in breast cancer patients and amplification of two putative oncogene-coamplification units: hst-1/int-2 and c-erbB-2/ear-1.
H. Tsuda (1989)
c-erbB-2 expression in benign and malignant breast disease.
B. Gusterson (1988)
HER-2/neu amplification predicts poor survival in node-positive breast cancer.
A. Borg (1990)
Amplification of the c-erb B-2 oncogene and prognosis of breast adenocarcinoma.
N. H. Heintz (1990)
Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer. An intergroup study.
E. Mansour (1989)
Proto-oncogene abnormalities in human breast cancer: correlations with anatomic features and clinical course of disease.
M. Cline (1987)
Adjuvant therapy for node-negative breast cancer.
W. Mcguire (1989)
Correlation between c-erbB-2 amplification and risk of recurrent disease in node-negative breast cancer.
M. Paterson (1991)
Direct interaction of a ligand for the erbB2 oncogene product with the EGF receptor and p185erbB2.
R. Lupu (1990)
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)
Immunohistochemical demonstration of growth factors, TGF-alpha, TGF-beta, IGF-I and neu oncogene product in benign and malignant human breast tissues.
Y. Mizukami (1990)
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)
The long term prognostic significance of c-erbB-2 in primary breast cancer.
J. Winstanley (1991)
How to use prognostic factors in axillary node-negative breast cancer patients.
W. Mcguire (1990)
Amplification of a novel v-erbB-related gene in a human mammary carcinoma.
C. R. King (1985)
Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer.
D. Slamon (1989)
Genetic alterations of c-myc, c-erbB-2, and c-Ha-ras protooncogenes and clinical associations in human breast carcinomas.
I. García (1989)
c-erbB-2 oncoprotein expression in primary and advanced breast cancer.
C. Lovekin (1991)
HER-2/neu oncogene protein and prognosis in breast cancer.
A. K. Tandon (1989)
Asymptotically Efficient Rank Invariant Test Procedures
R. Peto (1972)
Original article: Association of c-erbB-2 expression and S-phase fraction in the prognosis of node positive breast cancer
R. Anbazhagan (1991)
Diagnostic Histopathology of the Breast
D. Page (1988)
Prediction of relapse or survival in patients with node-negative breast cancer by DNA flow cytometry.
G. Clark (1989)
Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein overexpression in primary breast cancer.
S. Paik (1990)
The neu gene: an erbB-homologous gene distinct from and unlinked to the gene encoding the EGF receptor.
A. Schechter (1985)
Meeting highlights: adjuvant therapy for breast cancer.
J. H. Glick (1988)
Human breast cancer: identification of populations with a high risk of early relapse in relation to both oestrogen receptor status and c-erbB-2 overexpression.
E. May (1990)
The relationship between c-erbB-2 expression, S-phase fraction and prognosis in breast cancer.
S. O'Reilly (1991)
Immunohistochemical Study on Overexpression of c‐erbB‐2 Protein in Human Breast Cancer: Its Correlation with Gene Amplification and Long‐term Survival of Patients
H. Tsuda (1990)
A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor-positive tumors.
B. Fisher (1989)

This paper is referenced by
Monoclonal antibody to HER-2/neureceptor modulates repair of radiation-induced DNA damage and enhances radiosensitivity of human breast cancer cells overexpressing this oncogene.
R. Pietras (1999)
Her2/neu overexpression is associated with treatment failure in women with high-risk stage II and stage IIIA breast cancer (>10 involved lymph nodes) treated with high-dose chemotherapy and autologous hematopoietic progenitor cell support following standard-dose adjuvant chemotherapy.
J. Bitran (1996)
c-erbB-3 and c-erbB-2 protein expression in node-negative breast carcinoma--an immunocytochemical study.
G. Gasparini (1994)
HER-2 and choice of adjuvant chemotherapy in breast cancer.
S. Paik (2001)
Determination of c‐erbB‐2 Protein in Primary Breast Cancer Tissue Extract Using an Enzyme Immunoassay
T. Watanabe (1993)
Correlation between the In Vitro ATP-based Chemosensitivity Assay and HER2/neu Expression in Women with Breast Cancer
S. Woo (2007)
What the clinician needs from the pathologist: evidence-based reporting in breast cancer.
J. Going (2001)
The Role of HER2/neu Overexpression/Amplification in the Progression of Ductal Carcinoma In Situ to Invasive Carcinoma of the Breast
E. Latta (2002)
Induction of topoisomerase II activity after ErbB2 activation is associated with a differential response to breast cancer chemotherapy.
L. Harris (2001)
C-erbB-2 overexpression and survival in early onset breast cancer
M. Agrup (2004)
Intratumoral gene transfer of the Cytosine deaminase gene for the treatment of breast cancer.
H. Pandha (2000)
Overexpression of c-erbB2 is an independent marker of resistance to endocrine therapy in advanced breast cancer
S. Houston (1999)
Assessment of prognostic factors in breast fine-needle aspirates.
S. Masood (2000)
American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer.
L. Harris (2007)
Her2 assessment using quantitative reverse transcriptase polymerase chain reaction reliably identifies Her2 overexpression without amplification in breast cancer cases
G. Zoppoli (2017)
Overexpression of Her-2 in patients with poorly differentiated carcinoma or poorly differentiated adenocarcinoma of unknown primary site.
J. Hainsworth (2000)
Manysided herceptin action in HER2 overexpressing cells
Ewa Szacikowska (2003)
The prognostic role of HER 2 expression in ductal breast carcinoma in situ ( DCIS ) ; a population-based cohort study
S. Borgquist (2015)
Primary chemotherapy in breast invasive carcinoma: predictive value of the immunohistochemical detection of hormonal receptors, p53, c-erbB-2, MiB1, pS2 and GST pi.
G. MacGrogan (1996)
Very low-dose adjuvant chemotherapy in steroid receptor negative stage I breast cancer patients. Austrian Breast Cancer Study Group.
R. Jakesz (1998)
Prognostic relavance of cerbB2 expression following neoadjuvant chemotherapy in patients in a randomised trial of neoadjuvant versus adjuvant chemoendocrine therapy
R. Gregory (2004)
Treatment of early-stage breast cancer.
T. Hurd (1999)
Prognostic Factors in Breast Cancer
S. Masood (1997)
Macromolecular interstitial clearance, tumour vascularity, other prognostic factors and breast cancer survival
Ernest E. Sterns (2004)
Evaluation of HER-2 neu oncoprotein expression as a prognostic indicator of local recurrence in conservatively treated breast cancer: a case-control study.
B. Haffty (1996)
American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer.
A. Wolff (2007)
A Special Key for Unlocking the Door to Targeted Therapies of Breast Cancer
K. Lindemann (2008)
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)
Clinical significance of the quantitative assessment of the cytosolic concentration of HER-2/neu protein in breast cancer by immunoenzymatic assay (ELISA)
M. Corte (2005)
Anti-P-glycoprotein antibody C219 cross-reactivity with c-erbB2 protein: diagnostic and clinical implications.
H. Chan (1997)
Do we really need prognostic factors for breast cancer?
G. Clark (2004)
Prognostic and predictive indicators in operable breast cancer.
A. Morabito (2003)
See more
Semantic Scholar Logo Some data provided by SemanticScholar