Takayuki Iwamoto
   Department   Kawasaki Medical School  Kawasaki Medical School, Department of Breast and Thyroid Surgery,
   Position   Assistant Professor
Article types 原著
Language English
Peer review Peer reviewed
Title Prognostic impact of phosphorylated HER-2 in HER-2+ primary breast cancer.
Journal Formal name：The oncologist
Abbreviation：Oncologist
ISSN code：1549490X/10837159
Domestic / ForeginForegin
Volume, Issue, Page 16(7),pp.956-65
Author and coauthor 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
Authorship 2nd author
Publication date 2011
Summary 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.
DOI 10.1634/theoncologist.2010-0409
PMID 21712485