Open AccessPrognostic Impact of Phosphorylated HER‐2 in HER‐2 + Primary Breast Cancer
Author(s) -
Hayashi Naoki,
Iwamoto Takayuki,
GonzalezAngulo Ana M.,
FerrerLozano Jaime,
Lluch Ana,
Niikura Naoki,
Bartholomeusz Chandra,
Nakamura Seigo,
Hortobagyi Gabriel N.,
Ueno Naoto T.
Publication year - 2011
Publication title -
the oncologist
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.176
H-Index - 164
eISSN - 1549-490X
pISSN - 1083-7159
DOI - 10.1634/theoncologist.2010-0409
Subject(s) - medicine , breast cancer , oncology , cancer , primary (astronomy) , cancer research , physics , astronomy
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.