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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
O. Kallioniemi, K. Holli, T. Visakorpi, T. Koivula, H. Helin, J. Isola
Published 1991 · Medicine
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C‐erbB‐2 protein over‐expression was studied immunohis‐tochemically in 319 paraffin‐embedded breast carcinomas representing 89% of all breast‐cancer cases operated in the Tampere University Hospital between 1977 and 1981. The immunohistochemical evaluation of c‐erbB‐2 was optimized using protease pre‐treatment and verified using antibodies for both the external and the internal domains of the protein. c‐erbB‐2 over‐expression was found in 72 (23%) of the 319 cases and was associated with high histological and nuclear grade (p < 0.0001), DNA aneuploidy (p = 0.003), high tumor S‐phase fraction (p < 0.000l), and lack of estrogen (p < 0.0001) and progesterone (p = 0.03) receptors. Overall, breast‐cancer patients with c‐erbB‐2 over‐expression had about 2.2‐fold relative risk (RR) of death (p < 0.001) as compared with those without over‐expression. According to a multivariate analysis, c‐erbB‐2 over‐expression was an independent prognostic factor in the whole material as well as in the node‐negative sub‐set. In node‐negative breast‐cancer tumor size, S‐phase and c‐erbB‐2 status defined a large patient group with only 4% 5‐year and 15% 10‐year mortality rate without adjuvant therapy. In comparison with c‐erbB‐2‐negative tumors, those with over‐expression of this gene metastasized 3 times more often (p = 0.0002) to the lungs, liver and brain and 3 times less often to the bone. Our findings suggest that the prognostic value of c‐erbB‐2 over‐expression may be related not only to increased cell proliferation rate but also to a distinctive pattern of metastasis.
This paper references
Survival from first recurrence: relative importance of prognostic factors in 1,015 breast cancer patients.
G. Clark (1987)
Correlation of pretreatment proliferative activity of breast cancer with the response to cytotoxic chemotherapy.
Y. Remvikos (1989)
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)
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)
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)
Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases
C. Carter (1989)
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)
Analysis of c-erbB-2 expression in breast carcinomas with clinical follow-up.
A. Thor (1989)
Correlation between c-erbB-2 amplification and risk of recurrent disease in node-negative breast cancer.
M. Paterson (1991)
Improved prognostic impact of S-phase values from paraffin-embedded breast and prostate carcinomas after correcting for nuclear slicing.
O. Kallioniemi (1991)
Low metastatic potential of clone from murine colon adenocarcinoma 26 increased by transfection of activated c-erbB-2 gene.
Keisuke Yusa (1990)
OVEREXPRESSION OF THE c-erbB-2 ONCOPROTEIN IN HUMAN BREAST CARCINOMAS: IMMUNOHISTOLOGICAL ASSESSMENT CORRELATES WITH GENE AMPLIFICATION
DeonJ. Venter (1987)
NCL‐CB11, a new monoclonal antibody recognizing the internal domain of the c‐erbB‐2 oncogene protein effective for use on formalin‐fixed, paraffin‐embedded tissue
Ian P. Corbett (1990)
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)
Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer.
D. Slamon (1989)
The long‐term prognostic significance of the thymidine labelling index in breast cancer
M. Tubiana (1984)
Prediction of relapse or survival in patients with node-negative breast cancer by DNA flow cytometry.
G. Clark (1989)
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)
ERBB2 amplification in breast cancer with a high rate of proliferation.
A. Borg (1991)
HER-2/neu oncogene protein and prognosis in breast cancer.
A. K. Tandon (1989)
Improving the prognostic value of DNA flow cytometry in breast cancer by combining DNA index and S‐phase fraction: A proposed classification of DNA histograms in breast cancer
O. Kallioniemi (1988)
Indicators of prognosis in node-negative breast cancer.
H. Sigurdsson (1990)
Histological Grading and Prognosis in Breast Cancer
H. Bloom (1957)
The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity.
T. Akiyama (1986)
Expression of c-erbB-2 oncoprotein: a prognostic indicator in human breast cancer.
C. Wright (1989)
4. The role of the epidermal growth factor receptor and the c‐erbB‐2 protein in breast cancer
W. Gullick (1990)
The neu‐oncogene protein as a predictive factor for haematogenous metastases in breast cancer patients
C. D. de Potter (1990)
How to use prognostic factors in axillary node-negative breast cancer patients.
W. Mcguire (1990)
Structure and expression of c‐erbB‐2 and EGF receptor genes in inflammatory and non‐inflammatory breast cancer: Prognostic significance
M. Gue′rin (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)
This paper is referenced by
Evaluation of HER-2/NEU Protein Expression in Breast Cancer by Immunohistochemistry: An Interlaboratory Study Assessing the Reproducibility of HER-2/NEU Testing
D. Gancberg (2004)
HER-2-Positive Breast Cancer
Rupert Bartsch (2012)
The effect of early detection of occult brain metastases in HER2-positive breast cancer patients on survival and cause of death.
A. Niwińska (2010)
Aggressiveness of screen-detected breast cancers
M. Hakama (1995)
Immunodetection of bone marrow micrometastases in breast carcinoma patients and its correlation with primary tumour prognostic features.
S. Ménard (1994)
Increased risk of brain metastases in patients with HER‐2/neu‐positive breast carcinoma
R. Altaha (2005)
E2F3 is responsible for frequent amplification of 6p22.3 in human bladder cancer
M. Oeggerli (2007)
Expression of c-erbB-2 oncoprotein in transitional cell bladder cancer.
P. Lipponen (1993)
Breast cancer metastasis-associated genes : Prognostic significance and therapeutic implications
Moustafa As (1997)
MiR‐199b‐5p targets HER2 in breast cancer cells
Chen Fang (2013)
Her-2/neu Gene Amplification in Familial vs Sporadic Breast Cancer
A. Espinosa (2003)
Isolated central nervous system metastases in patients with HER2-overexpressing advanced breast cancer treated with first-line trastuzumab-based therapy.
H. Burstein (2005)
Site-specific relapse pattern of the triple negative tumors in Chinese breast cancer patients
Yanping Lin (2009)
Treatment of Brain Metastases: Chemotherapy
S. Grimm (2011)
HER-2/neu in Breast Cancer: A Possible Means of Therapy?
T. Brodowicz (1998)
Prognostic factors for node-negative breast cancers: Results of a study program by the Japanese breast cancer society
S. Umemura (1998)
Flow Cytometric and Immunohistochemical Correlations in High Incidence Human Solid Tumors
D. Danesi (1997)
Measures of cell turnover (proliferation and apoptosis) and their association with survival in breast cancer.
S. Liu (2001)
Results from an observational trial with oral vinorelbine and trastuzumab in advanced breast cancer
R. Bartsch (2006)
Behandlung der Patientinnen mit HER2- (ErbB2-) positivem Mammakarzinom
Michael Untch (2009)
Cerebral metastases in metastatic breast cancer: disease-specific risk factors and survival.
F. Heitz (2011)
Targeted therapy - the new hopes in breast cancer treatment
R. Duchnowska (2007)
High cell proliferation activity determined by DNA flow cytometry and prognosis in epidermoid lung carcinoma.
T. Visakorpi (1995)
Mutual Predictive Value of c-erbB-2 Overexpression and Various Prognostic Factors in Ductal Invasive Breast Carcinoma
J. Jakić-Razumović (2000)
Her-2/neu Status in Syrian Women with Breast Carcinoma: A Syrian Cohort Study of more than 10000 Cases
M. Salamoon (2018)
Prognostic significance of Ki‐67 and topoisomerase IIα expression in infiltrating ductal carcinoma of the breast
P. Rudolph (2004)
The relationship between prognostic and predictive factors in the management of breast cancer
I. C. Henderson (2004)
Quantitative analysis of p185HER‐2/neu protein in breast cancer and its association with other prognostic factors
P. Valerón (1997)
Concurrent overexpression of p53 and c-erbB-2 correlates with accelerated cycling and concomitant poor prognosis in node-negative breast cancer.
P. Rudolph (2001)
Trastuzumab in the treatment of HER2 positive breast cancer
M. Summerhayes (2001)
HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues.
M. A. Owens (2004)
Her-2/neu amplification and breast cancer survival: results from the Shanghai breast cancer study.
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