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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
10.1200/JCO.1987.5.1.55
Survival from first recurrence: relative importance of prognostic factors in 1,015 breast cancer patients.
G. Clark (1987)
10.1093/JNCI/81.18.1383
Correlation of pretreatment proliferative activity of breast cancer with the response to cytotoxic chemotherapy.
Y. Remvikos (1989)
10.1056/NEJM198902233200801
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)
10.1126/SCIENCE.2999974
Tyrosine kinase receptor with extensive homology to EGF receptor shares chromosomal location with neu oncogene.
L. Coussens (1985)
10.1126/SCIENCE.3798106
Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.
D. Slamon (1987)
10.1002/1097-0142(19890101)63:1<181::AID-CNCR2820630129>3.0.CO;2-H
Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases
C. Carter (1989)
10.1056/NEJM198811103191902
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)
10.1002/CYTO.990120506
Improved prognostic impact of S-phase values from paraffin-embedded breast and prostate carcinomas after correcting for nuclear slicing.
O. Kallioniemi (1991)
10.1093/JNCI/82.20.1633
Low metastatic potential of clone from murine colon adenocarcinoma 26 increased by transfection of activated c-erbB-2 gene.
Keisuke Yusa (1990)
10.1016/S0140-6736(87)92736-X
OVEREXPRESSION OF THE c-erbB-2 ONCOPROTEIN IN HUMAN BREAST CARCINOMAS: IMMUNOHISTOLOGICAL ASSESSMENT CORRELATES WITH GENE AMPLIFICATION
DeonJ. Venter (1987)
10.1002/PATH.1711610105
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)
10.1200/JCO.1990.8.1.103
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)
10.1126/SCIENCE.2470152
Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer.
D. Slamon (1989)
10.1002/IJC.2910330404
The long‐term prognostic significance of the thymidine labelling index in breast cancer
M. Tubiana (1984)
10.1056/NEJM198903093201003
Prediction of relapse or survival in patients with node-negative breast cancer by DNA flow cytometry.
G. Clark (1989)
10.1056/NEJM198902233200802
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)
10.1200/JCO.1989.7.8.1120
HER-2/neu oncogene protein and prognosis in breast cancer.
A. K. Tandon (1989)
10.1002/1097-0142(19881115)62:10<2183::AID-CNCR2820621019>3.0.CO;2-B
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)
10.1056/NEJM199004123221505
Indicators of prognosis in node-negative breast cancer.
H. Sigurdsson (1990)
10.1038/bjc.1957.43
Histological Grading and Prognosis in Breast Cancer
H. Bloom (1957)
10.1126/SCIENCE.3012781
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)
10.1002/IJC.2910460708
4. The role of the epidermal growth factor receptor and the c‐erbB‐2 protein in breast cancer
W. Gullick (1990)
10.1002/IJC.2910450112
The neu‐oncogene protein as a predictive factor for haematogenous metastases in breast cancer patients
C. D. de Potter (1990)
10.1093/JNCI/82.12.1006
How to use prognostic factors in axillary node-negative breast cancer patients.
W. Mcguire (1990)
10.1002/IJC.2910430205
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
10.1023/A:1016146130767
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)
10.2165/00063030-200721020-00001
HER-2-Positive Breast Cancer
Rupert Bartsch (2012)
10.1016/j.ijrobp.2009.06.030
The effect of early detection of occult brain metastases in HER2-positive breast cancer patients on survival and cause of death.
A. Niwińska (2010)
10.1016/S0140-6736(95)90223-6
Aggressiveness of screen-detected breast cancers
M. Hakama (1995)
10.1038/bjc.1994.221
Immunodetection of bone marrow micrometastases in breast carcinoma patients and its correlation with primary tumour prognostic features.
S. Ménard (1994)
10.1002/cncr.20813
Increased risk of brain metastases in patients with HER‐2/neu‐positive breast carcinoma
R. Altaha (2005)
10.5451/UNIBAS-004237488
E2F3 is responsible for frequent amplification of 6p22.3 in human bladder cancer
M. Oeggerli (2007)
10.1016/S0959-8049(05)80360-0
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)
10.1002/jcb.24487
MiR‐199b‐5p targets HER2 in breast cancer cells
Chen Fang (2013)
10.1309/5h778w5k75cmm03w
Her-2/neu Gene Amplification in Familial vs Sporadic Breast Cancer
A. Espinosa (2003)
10.1093/ANNONC/MDI371
Isolated central nervous system metastases in patients with HER2-overexpressing advanced breast cancer treated with first-line trastuzumab-based therapy.
H. Burstein (2005)
10.1186/1471-2407-9-342
Site-specific relapse pattern of the triple negative tumors in Chinese breast cancer patients
Yanping Lin (2009)
10.1007/s11912-011-0211-y
Treatment of Brain Metastases: Chemotherapy
S. Grimm (2011)
10.1007/978-3-642-80466-3_11
HER-2/neu in Breast Cancer: A Possible Means of Therapy?
T. Brodowicz (1998)
10.1007/BF02966703
Prognostic factors for node-negative breast cancers: Results of a study program by the Japanese breast cancer society
S. Umemura (1998)
10.1177/030089169708300313
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)
10.1007/s10549-006-9342-5
Results from an observational trial with oral vinorelbine and trastuzumab in advanced breast cancer
R. Bartsch (2006)
10.1007/s00761-009-1648-6
Behandlung der Patientinnen mit HER2- (ErbB2-) positivem Mammakarzinom
Michael Untch (2009)
10.1093/annonc/mdq625
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)
10.3109/02841869509094035
High cell proliferation activity determined by DNA flow cytometry and prognosis in epidermoid lung carcinoma.
T. Visakorpi (1995)
10.1177/030089160008600106
Mutual Predictive Value of c-erbB-2 Overexpression and Various Prognostic Factors in Ductal Invasive Breast Carcinoma
J. Jakić-Razumović (2000)
10.18689/mjcsr-1000109
Her-2/neu Status in Syrian Women with Breast Carcinoma: A Syrian Cohort Study of more than 10000 Cases
M. Salamoon (2018)
10.1023/A:1006159016703
Prognostic significance of Ki‐67 and topoisomerase IIα expression in infiltrating ductal carcinoma of the breast
P. Rudolph (2004)
10.1023/A:1006141703224
The relationship between prognostic and predictive factors in the management of breast cancer
I. C. Henderson (2004)
10.1002/(SICI)1097-0215(19970422)74:2<175::AID-IJC6>3.0.CO;2-W
Quantitative analysis of p185HER‐2/neu protein in breast cancer and its association with other prognostic factors
P. Valerón (1997)
10.1053/HUPA.2001.22748
Concurrent overexpression of p53 and c-erbB-2 correlates with accelerated cycling and concomitant poor prognosis in node-negative breast cancer.
P. Rudolph (2001)
10.1191/1078155201jp076oa
Trastuzumab in the treatment of HER2 positive breast cancer
M. Summerhayes (2001)
10.3816/CBC.2004.N.011
HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues.
M. A. Owens (2004)
10.3892/OR.19.5.1347
Her-2/neu amplification and breast cancer survival: results from the Shanghai breast cancer study.
A. Beeghly-Fadiel (2008)
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