Prognostic impact of phosphorylated HER-2 in HER-2 + primary breast cancer

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

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Purpose. Tyrosine 1248 is one of the autophosphory-lation 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%).

Original languageEnglish
Pages (from-to)956-965
Number of pages10
JournalOncologist
Volume16
Issue number7
DOIs
Publication statusPublished - Jul 2011

Fingerprint

Breast Neoplasms
Disease-Free Survival
ROC Curve
Tyrosine
Survival Rate
Protein Array Analysis
Proportional Hazards Models
Multivariate Analysis

Keywords

  • Breast cancer
  • HER-2
  • Metastases
  • Phosphorylation
  • Reverse-phase protein array

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Hayashi, N., Iwamoto, T., Gonzalez-Angulo, A. M., Ferrer-Lozano, J., Lluch, A., Niikura, N., ... Ueno, N. T. (2011). Prognostic impact of phosphorylated HER-2 in HER-2 + primary breast cancer. Oncologist, 16(7), 956-965. https://doi.org/10.1634/theoncologist.2010-0409

Prognostic impact of phosphorylated HER-2 in HER-2 + primary breast cancer. / Hayashi, Naoki; Iwamoto, Takayuki; Gonzalez-Angulo, Ana M.; Ferrer-Lozano, Jaime; Lluch, Ana; Niikura, Naoki; Bartholomeusz, Chandra; Nakamura, Seigo; Hortobagyi, Gabriel N.; Ueno, Naoto T.

In: Oncologist, Vol. 16, No. 7, 07.2011, p. 956-965.

Research output: Contribution to journalArticle

Hayashi, N, Iwamoto, T, Gonzalez-Angulo, AM, Ferrer-Lozano, J, Lluch, A, Niikura, N, Bartholomeusz, C, Nakamura, S, Hortobagyi, GN & Ueno, NT 2011, 'Prognostic impact of phosphorylated HER-2 in HER-2 + primary breast cancer', Oncologist, vol. 16, no. 7, pp. 956-965. https://doi.org/10.1634/theoncologist.2010-0409
Hayashi N, Iwamoto T, Gonzalez-Angulo AM, Ferrer-Lozano J, Lluch A, Niikura N et al. Prognostic impact of phosphorylated HER-2 in HER-2 + primary breast cancer. Oncologist. 2011 Jul;16(7):956-965. https://doi.org/10.1634/theoncologist.2010-0409
Hayashi, Naoki ; Iwamoto, Takayuki ; Gonzalez-Angulo, Ana M. ; Ferrer-Lozano, Jaime ; Lluch, Ana ; Niikura, Naoki ; Bartholomeusz, Chandra ; Nakamura, Seigo ; Hortobagyi, Gabriel N. ; Ueno, Naoto T. / Prognostic impact of phosphorylated HER-2 in HER-2 + primary breast cancer. In: Oncologist. 2011 ; Vol. 16, No. 7. pp. 956-965.
@article{e4b01e556db440b395d522315cfa1b70,
title = "Prognostic impact of phosphorylated HER-2 in HER-2 + primary breast cancer",
abstract = "Purpose. Tyrosine 1248 is one of the autophosphory-lation 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{\%}).",
keywords = "Breast cancer, HER-2, Metastases, Phosphorylation, Reverse-phase protein array",
author = "Naoki Hayashi and Takayuki Iwamoto and Gonzalez-Angulo, {Ana M.} and Jaime Ferrer-Lozano and Ana Lluch and Naoki Niikura and Chandra Bartholomeusz and Seigo Nakamura and Hortobagyi, {Gabriel N.} and Ueno, {Naoto T.}",
year = "2011",
month = "7",
doi = "10.1634/theoncologist.2010-0409",
language = "English",
volume = "16",
pages = "956--965",
journal = "Oncologist",
issn = "1083-7159",
publisher = "AlphaMed Press",
number = "7",

}

TY - JOUR

T1 - Prognostic impact of phosphorylated HER-2 in HER-2 + primary breast cancer

AU - Hayashi, Naoki

AU - Iwamoto, Takayuki

AU - Gonzalez-Angulo, Ana M.

AU - Ferrer-Lozano, Jaime

AU - Lluch, Ana

AU - Niikura, Naoki

AU - Bartholomeusz, Chandra

AU - Nakamura, Seigo

AU - Hortobagyi, Gabriel N.

AU - Ueno, Naoto T.

PY - 2011/7

Y1 - 2011/7

N2 - Purpose. Tyrosine 1248 is one of the autophosphory-lation 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%).

AB - Purpose. Tyrosine 1248 is one of the autophosphory-lation 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%).

KW - Breast cancer

KW - HER-2

KW - Metastases

KW - Phosphorylation

KW - Reverse-phase protein array

UR - http://www.scopus.com/inward/record.url?scp=79960875009&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79960875009&partnerID=8YFLogxK

U2 - 10.1634/theoncologist.2010-0409

DO - 10.1634/theoncologist.2010-0409

M3 - Article

C2 - 21712485

AN - SCOPUS:79960875009

VL - 16

SP - 956

EP - 965

JO - Oncologist

JF - Oncologist

SN - 1083-7159

IS - 7

ER -