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

Abstract

BACKGROUNDThe 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.METHODSTissue 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.RESULTSUsing 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.CONCLUSIONSIn 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.

Effects of the combined blockade of EGFR and ErbB-2 on signal transduction and regulation of cell cycle regulatory proteins in breast cancer cells

“…These data clearly establish a link in vivo between expression of EGFR and activation of ErbB-2 in breast cancer patients. In agreement with these findings, co-expression of EGFR, ErbB-2 and ErbB-3 was also found to have a negative synergistic effect on patient outcome, independent of tumor size or lymph node status [9]. Different anti-EGFR agents, including the EGFR tyrosine kinase inhibitor (EGFR-TKI) gefitinib (ZD1839, Iressa), have shown to inhibit the growth of human breast carcinoma cells [10][11][12][13][14].…”

Expression of basal keratins and vimentin in breast cancers of young women correlates with adverse pathologic parameters

“…28,31,32 Coexpression of HER-1, HER-2 and HER-3 was demonstrated to have a negative synergistic effect on patient outcome. 33 These studies further showed that expression of basal cytokeratins and vimentin are associated with more aggressive tumor features and poorer disease prognosis.…”

Adoptive immunotherapy using human peripheral blood lymphocytes transferred with RNA encoding Her-2/neu-specific chimeric immune receptor in ovarian cancer xenograft model

“…Despite of early treatment with surgical and chemotherapy, women with disease having Her-2/neu amplification shows poor disease-free survival due to its aggressive form. [19][20][21][22] Many methods have been used to therapeutically target Her-2-overexpressing cancers, including the use of anti-Her-2/neu antibodies. [23][24][25][26] Trastuzumab also known as Herceptin for humanized form, was found to inhibit the proliferation of human cancer cells that overexpress Her-2/neu, both in vitro and in vivo.…”