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

• Published in: Cancer Vol. 103; no. 9; pp. 1770 - 1777
• Main Authors: Wiseman, Sam M., Makretsov, Nikita, Nielsen, Torsten O., Gilks, Blake, Yorida, Erika, Cheang, Maggie, Turbin, Dmitry, Gelmon, Karen, Huntsman, David G.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.05.2005
• Subjects: Biomarkers, Tumor - metabolism; breast carcinoma; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Drug Synergism; Female; Gene Expression Regulation, Neoplastic; HER‐1; HER‐2; HER‐3; HER‐4; Humans; Lymph Nodes - pathology; Neoplasm Invasiveness - pathology; Neoplasm Staging; Prognosis; Receptor, Epidermal Growth Factor - metabolism; Receptor, ErbB-2 - metabolism; Receptor, ErbB-3 - metabolism; Receptor, ErbB-4; Survival Rate; tissue microarray
• ISSN: 0008-543X; 1097-0142
• DOI: 10.1002/cncr.20970

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. In a cohort of 242 patients diagnosed with invasive breast carcinoma, the authors observed type 1 growth factor (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. Such patients may potentially benefit from therapy simultaneously targeting several TIGFR family members.