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Neu/erbB-2 Amplification Identifies A Poor-prognosis Group Of Women With Node-negative Breast Cancer. Toronto Breast Cancer Study Group.
I. Andrulis, S. Bull, M. Blackstein, D. Sutherland, C. Mak, S. Sidlofsky, K. P. Pritzker, R. Hartwick, W. Hanna, L. Lickley, R. Wilkinson, A. Qizilbash, U. Ambus, M. Lipa, H. Weizel, A. Katz, M. Baida, S. Mariz, G. Stoik, P. Dacamara, D. Strongitharm, W. Geddie, D. McCready
Published 1998 · Medicine
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PURPOSE It remains a challenge to predict which women with axillary node-negative (ANN) breast cancer at greatest risk of relapse may benefit most from adjuvant therapy. Increases in neu/erbB-2 have been implicated in breast cancer prognosis. Although overexpression has been investigated extensively, this study represents the first prospective assessment of the prognostic value of neu/erbB-2 DNA amplification in a cohort of women with newly diagnosed ANN. METHODS A consecutive series of women was monitored for recurrence (median follow-up duration, 36 months) and tumors from 580 individuals were analyzed for amplification. The association of amplification with risk of recurrence was examined in survival analyses with traditional and histologic markers as prognostic factors. RESULTS Neu/erbB-2 was amplified in 20% of cases. We found an increased risk of disease recurrence when neu/erbB-2 was amplified > or = twofold that persisted with adjustment for other prognostic factors (relative risk, 2.36; P = .002). We found some evidence that amplification was more important in patients who received chemotherapy compared with untreated patients. CONCLUSION neu/erbB-2 amplification is an independent prognostic factor for risk of recurrence in ANN breast cancer. Women with tumors without neu/erbB-2 amplification have a good prognosis; aggressive therapy in this group is therefore difficult to justify. On the other hand, even with adjuvant chemotherapeutic treatment, women whose tumors exhibit neu/erbB-2 amplification have an increased risk of recurrence. We encourage a randomized trial to compare more aggressive adjuvant chemotherapy versus standard chemotherapy for ANN women whose tumors exhibit neu/erbB-2 amplification.
This paper references
Interobserver variation in the identification of breast carcinoma in intramammary lymphatics.
K. Gilchrist (1982)
Histologic grading of breast cancer.
E. Fisher (1980)
Detailed deletion mapping with a refined physical map of 7q31 localizes a putative tumor suppressor gene for breast cancer in the region of MET.
J. C. Lin (1996)
Histological Grading and Prognosis in Breast Cancer
H. Bloom (1957)
Relationship among outcome, stage of disease, and histologic grade for 22,616 cases of breast cancer. The basis for a prognostic index
D. Henson (1991)
Efficacy of adjuvant chemotherapy in high-risk node-negative breast cancer. An intergroup study.
E. Mansour (1989)
Refined localization of the asparagine synthetase gene (ASNS) to chromosome 7, region q21.3, and characterization of the somatic cell hybrid line 4AF/106/KO15.
H. Heng (1994)
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)
Regression models and life tables (with discussion
D. Cox (1972)
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)
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)
Amplification of a novel v-erbB-related gene in a human mammary carcinoma.
C. R. King (1985)
Role of steroid hormone receptors as prognostic factors in primary breast cancer.
W. Mcguire (1986)
Relation of number of positive axillary nodes to the prognosis of patients with primary breast cancer. An NSABP update
B. Fisher (1983)
Prognostic importance of c-erbB-2 expression in breast cancer. International (Ludwig) Breast Cancer Study Group.
B. Gusterson (1992)
Correlation of c-erbB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading.
M. Berger (1988)
Clinical significance of HER-2/neu oncogene amplification in primary breast cancer. The South Australian Breast Cancer Study Group.
R. Seshadri (1993)
Proportional hazards tests and diagnostics based on weighted residuals
P. Grambsch (1994)
HER-2/neu oncogene protein and prognosis in breast cancer.
A. K. Tandon (1989)
Distribution and patterns of staining of Neu oncogene product in benign and malignant breast diseases.
W. Hanna (1990)
Expression of c-erbB-2 oncoprotein: a prognostic indicator in human breast cancer.
C. Wright (1989)
pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long‐term follow‐up
C. Elston (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)
HER-2/neu in node-negative breast cancer: prognostic significance of overexpression influenced by the presence of in situ carcinoma.
D. Allred (1992)
Her-2/neu expression in node-negative breast cancer: direct tissue quantitation by computerized image analysis and association of overexpression with increased risk of recurrent disease.
M. Press (1993)
c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer.
H. Muss (1994)
Systemic treatment of early breast cancer by hormonal, cytotoxic, or immune therapy. 133 randomised trials involving 31,000 recurrences and 24,000 deaths among 75,000 women. Early Breast Cancer Trialists' Collaborative Group.
A. Howell (1992)
Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer.
D. Slamon (1989)
Correlation between c-erbB-2 amplification and risk of recurrent disease in node-negative breast cancer.
M. Paterson (1991)
Prognostic significance of peritumoral lymphatic and blood vessel invasion in node-negative carcinoma of the breast.
A. K. Lee (1990)
Prolonged disease-free survival after one course of perioperative adjuvant chemotherapy for node-negative breast cancer.
A. Goldhirsch (1989)
c-erbB-2 amplification in node-negative human breast cancer.
J. Ro (1989)
Tables of the number of patients required in clinical trials using the logrank test.
L. Freedman (1982)
Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.
D. Slamon (1987)
Relative risk trees for censored survival data.
M. Leblanc (1992)
Peritumoral lymphatic invasion in patients with node‐negative mammary duct carcinoma
Claudio G. Clemente (1992)
Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases
C. Carter (1989)
(C-A)n microsatellite repeat D7S522 is the most commonly deleted region in human primary breast cancer.
J. Zenklusen (1994)
This paper is referenced by
The Clinicopathologic Significance of Centromere 17 Copy Number Alterations in Invasive Breast Carcinoma
Uma Krishnamurti (2014)
HER2/neu Immunostaining in Invasive Breast Cancer: Analysis of False Positive Factors.
M. Arafah (2010)
What the clinician needs from the pathologist: evidence-based reporting in breast cancer.
J. Going (2001)
Comparison of HER2/neu status assessed by quantitative polymerase chain reaction and immunohistochemistry.
F. O'Malley (2001)
Prognostic factors affecting disease-free survival rate following surgical resection of primary breast cancer.
K. Horita (2001)
Chapter 17 – Immunohistology of the Breast
D. Dabbs (2006)
The Role of HER2/neu Overexpression/Amplification in the Progression of Ductal Carcinoma In Situ to Invasive Carcinoma of the Breast
E. Latta (2002)
The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine.
J. Ross (2009)
Transgenic mouse models of human breast cancer
J. Hutchinson (2000)
Human epidermal growth factor receptor 2 oncoprotein expression in breast cancer patients from central Anatolia, Turkey
H. Çoşkun (2009)
Procédés de traitement d'un cancer positif her2
S. Y. Chui (2016)
JAG1 expression is associated with a basal phenotype and recurrence in lymph node-negative breast cancer
M. Reedijk (2007)
Quantitative association between HER-2/neu and steroid hormone receptors in hormone receptor-positive primary breast cancer.
G. Konecny (2003)
Evidence for the use of chemotherapy in breast cancer
J. Nabholtz (2002)
ErbB-4 expression in limb soft-tissue sarcoma: correlation with the results of neoadjuvant chemotherapy.
O. Merimsky (2002)
Update of Recommendat ions for the Use of Tumor Markers in Breast and Colorecta l Cancer : Cl in ica l Pract ice Guidel ines of the American Socie ty of Cl in ica l Oncology *
R. Bast (2001)
HER-2 is an independent prognostic factor in endometrial cancer: association with outcome in a large cohort of surgically staged patients.
C. Morrison (2006)
Targeted disruption of ErbB2/Neu in the mammary epithelium results in impaired ductal outgrowth
E. Andrechek (2005)
Beyond lymph node staging: molecular predictors of outcome in breast cancer.
David G Sheldon (2005)
Multifractal-based nuclei segmentation in fish images
Nikola Reljin (2017)
Molecular analysis of local relapse in high-risk breast cancer patients: can radiotherapy fractionation and time factors make a difference?
M. Koukourakis (2003)
Weekly T rastuzumab a nd P aclitaxel T herapy f or M etastatic Breast C ancer W ith A nalysis o f E fficacy b y HER2 Immunophenotype a nd G ene A mplification
A. Seidman (2001)
Treatment of early-stage breast cancer.
T. Hurd (1999)
Complexity of signal transduction mediated by ErbB2: Clues to the potential of receptor-targeted cancer therapy
P. Nagy (2008)
Cell cycle regulated phosphorylation of LIMD1 in cell lines and expression in human breast cancers.
Christopher J. Huggins (2008)
Prognostic and predictive value of HER2/neu oncogene in breast cancer
S. Masood (2002)
Vaccination with human HER-2/neu (435-443) CTL peptide induces effective antitumor immunity against HER-2/neu-expressing tumor cells in vivo.
A. Gritzapis (2006)
Real-time PCR complements immunohistochemistry in the determination of HER-2/neu status in breast cancer
A. Nistor (2006)
Predicting tissue HER2 status using serum HER2 levels in patients with metastatic breast cancer.
Sun-Young Kong (2006)
Reproductive history determines ErbB2 locus amplification, WNT signalling and tumour phenotype in a murine breast cancer model
Liliana D. Ordonez (2020)
Insights from mixture cure modeling of molecular markers for prognosis in breast cancer.
Yildiz E Yilmaz (2013)
The Clinicopathologic Characteristics and Clinical Outcomes of Estrogen Receptor-Negative and Progesterone Receptor-Positive Breast Cancer.
Suk-Bok Kang (2009)See more