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Coexpression of the type 1 growth factor receptor family members HER‐1, HER‐2, and HER‐3 has a synergistic negative prognostic effect on breast carcinoma survival
Author(s) -
Wiseman Sam M.,
Makretsov Nikita,
Nielsen Torsten O.,
Gilks Blake,
Yorida Erika,
Cheang Maggie,
Turbin Dmitry,
Gelmon Karen,
Huntsman David G.
Publication year - 2005
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.20970
Subject(s) - medicine , oncology , breast carcinoma , univariate analysis , breast cancer , tissue microarray , proportional hazards model , survival analysis , multivariate analysis , lymph node , log rank test , immunohistochemistry , carcinoma , pathology , cancer
BACKGROUND The clinical significance of coexpression of type 1 growth factor receptor (T1GFR) family members remains largely unknown. The objective of the current study was to determine the frequency and the possible prognostic effect of coexpression of HER‐1, HER‐2, HER‐3, and HER‐4 by breast carcinoma. METHODS Tissue microarrays were constructed using clinically annotated formalin‐fixed, paraffin‐embedded tumor samples from 242 patients with invasive breast carcinomas with a median 15‐year follow‐up. The levels of TIGFR family members (HER‐1–HER‐4) were measured by immunohistochemistry. K‐means clustering algorithm, as well as univariate (Kaplan–Meier, log‐rank test) and multivariate (Cox regression) survival analyses were applied to the data set. RESULTS Using univariate analysis, expression of HER‐1, HER‐2, and HER‐3, but not HER‐4, was significantly associated with decreased patient disease‐specific survival ( P < 0.05). Kaplan–Meier survival analysis showed that coexpression of ≥ 2 of HER‐1, HER‐2, and HER‐3 in any combination was associated with reduced patient disease‐specific survival compared with single marker expression or no expression (35% vs. 65% vs. 78% 10‐year survival rates, P = 0.001). Using multivariate analysis, expression of ≥ 2 of HER‐1, HER‐2, and HER‐3 was independent of lymph node status and tumor size. CONCLUSIONS In a cohort of patients with breast carcinoma, the authors observed T1GFR family member coexpression (HER‐1, HER‐2, and HER‐3) to have a negative synergistic effect on patient outcome, independent of tumor size or lymph node status. Thus, coexpression of T1GFR family members identified a subset of patients with a poor disease prognosis who may potentially benefit from therapy simultaneously targeting several T1GFR family members. Cancer 2005. © 2005 American Cancer Society.