Document Detail


Prognostic impact of phosphorylated HER-2 in HER-2+ primary breast cancer.
MedLine Citation:
PMID:  21712485     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: Tyrosine 1248 is one of the autophosphorylation sites of human epidermal growth factor receptor (HER)-2. We determined the prognostic value of the expression level of tyrosine 1248-phosphorylated HER-2 (pHER-2) in patients with HER-2(+) primary breast cancer using a reverse-phase protein array.
PATIENTS AND METHODS: The optimal cutoff value of pHER-2 for segregating disease-free survival (DFS) was determined by receiver operating characteristic (ROC) curve analysis. Five-year DFS for pHER-2 expression level was estimated with the Kaplan-Meier method using both derivation (n = 162) and validation (n = 227) cohorts.
RESULTS: Of the 162 patients in the derivation cohort, 26 had high HER-2 expression levels. The area under the ROC curve for pHER-2 level and DFS was 0.662. Nineteen of the 162 patients (11.7%) had high pHER-2 expression levels (pHER-2(high)); 143 patients (88.3%) had low pHER-2 expression levels (pHER-2(low)). Among the 26 patients with high HER-2 expression levels, the 17 pHER-2(high) patients had a significantly lower 5-year DFS rate than the nine pHER-2(low) patients (23.5% versus 77.8%). On multivariate analysis, only pHER-2(high) independently predicted DFS in the Cox proportional hazards model. In the validation cohort, among 61 patients with high HER-2 expression, the difference in 5-year DFS rates between pHER-2(high) (n = 7) and pHER-2(low) (n = 54) patients was marginal (57.1% versus 81.5%).
CONCLUSION: In patients with HER-2(+) primary breast cancer, pHER-2(high) patients had a lower 5-year DFS rate than pHER-2(low) patients. Quantification of pHER-2 expression level may provide prognostic information beyond the current standard HER-2 status.
Authors:
Naoki Hayashi; Takayuki Iwamoto; Ana M Gonzalez-Angulo; Jaime Ferrer-Lozano; Ana Lluch; Naoki Niikura; Chandra Bartholomeusz; Seigo Nakamura; Gabriel N Hortobagyi; Naoto T Ueno
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-06-28
Journal Detail:
Title:  The oncologist     Volume:  16     ISSN:  1549-490X     ISO Abbreviation:  Oncologist     Publication Date:  2011  
Date Detail:
Created Date:  2011-08-01     Completed Date:  2012-01-31     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  9607837     Medline TA:  Oncologist     Country:  United States    
Other Details:
Languages:  eng     Pagination:  956-65     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Breast Neoplasms / enzymology*,  genetics,  pathology
Disease-Free Survival
Female
Humans
Immunohistochemistry
In Situ Hybridization, Fluorescence
Middle Aged
Phosphorylation
Prognosis
Receptor, erbB-2 / biosynthesis,  genetics,  metabolism*
Grant Support
ID/Acronym/Agency:
1K23CA121994-01/CA/NCI NIH HHS; 1R21CA120248-01/CA/NCI NIH HHS; CA016672/CA/NCI NIH HHS; K23 CA121994/CA/NCI NIH HHS; K23 CA121994-01/CA/NCI NIH HHS; P30 CA016672/CA/NCI NIH HHS; P30 CA016672-36/CA/NCI NIH HHS; R01 CA123318/CA/NCI NIH HHS; R01 CA123318-01/CA/NCI NIH HHS; R01 CA123318-01A1/CA/NCI NIH HHS; R01 CA123318-02/CA/NCI NIH HHS; R01 CA123318-03/CA/NCI NIH HHS; R01 CA123318-04/CA/NCI NIH HHS; R01 CA123318-05/CA/NCI NIH HHS; R01 CA123318-06/CA/NCI NIH HHS; R21 CA120248/CA/NCI NIH HHS; R21 CA120248-01/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
EC 2.7.10.1/Receptor, erbB-2
Comments/Corrections

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