Evaluation of the prognostic and predictive value of HER family mRNA expression in high-risk early breast cancer: A Hellenic Cooperative Oncology Group (HeCOG) study

Abstract

The aim of the study was to evaluate the prognostic ability of the transcriptional profiling of the HER family genes in early breast cancer, as well as to investigate the predictive value of HER2 mRNA expression for adjuvant treatment with paclitaxel. RNA was extracted from 268 formalin-fixed paraffin-embedded (FFPE) tumour tissue samples of high-risk breast cancer patients enrolled in the randomised HE10/97 trial, evaluating the effect of dose-dense anthracycline-based sequential adjuvant chemotherapy with or without paclitaxel. The mRNA expression of all four HER family members was assessed by kinetic reverse transcription-polymerase chain reaction (kRT -PCR). The overall concordance between kRT -PCR and IHC/FISH for HER2 status determination was 74%. At a median follow-up of 8 years, multivariate analysis showed that EGFR and HER2 mRNA expression was associated with reduced overall survival (OS). HER3 and HER4 mRNA level had a favourable prognostic value in terms of OS and disease-free survival (DFS), respectively. Adjusting for HER2 mRNA expression, OS and DFS did not differ between treatment groups. These data indicate that EGFR as well as HER2 are prognostic factors of worse clinical outcomes, whereas HER3 and HER4 gene transcription is associated with better prognosis in high-risk early breast cancer. However, HER2 mRNA expression did not predict clinical benefit from paclitaxel. Kinetic RT -PCR represents an alternative method for evaluating the expression of HER family members in FFPE breast carcinomas.

Prognostic Significance of Human Epidermal Receptor (HER)-3 Immunohistochemical Expression in Patients with Metastatic Breast Cancer

“…In line with these findings, HER-3 gene amplification has been associated with a reduced disease-free survival and shorter relapse-free survival rates (Bieche et al, 2003;Sassen et al, 2008). However, at least other three studies have reported opposite findings, with better outcomes associated with a positive HER-3 expression (Pawlowski et al, 2000;Lee et al, 2007;Koutras et al, 2008). One potential explanation for the discrepant findings regarding the prognostic value of HER-3 expression levels may be that clinical outcomes can also be influenced by its phosphorylation level or the expression of HER-3 ligands (Koutras et al, 2010).…”

High EGFR mRNA expression is a prognostic factor for reduced survival in pancreatic cancer after gemcitabine-based adjuvant chemotherapy

“…Immunohistochemical analysis is a valid method as it shows protein expression. However, the clinical introduction of immunohistochemical assessment for predicting sensitivity to chemotherapeutic agents is still problematic due to difficulties in quantitative measurement (inter-observer variations in interpretation) and the lack of calibrated quantification techniques (27)(28)(29). in addition, only 10-20% of patients with PDAC are candidates for curative resection (3).…”

WW domain containing E3 ubiquitin protein ligase 1 targets the full-length ErbB4 for ubiquitin-mediated degradation in breast cancer

“…Unlike other ErbB family members, ErbB4 may have tumor-suppressor activities because ErbB4 decreases breast epithelial cell proliferation (Pitfield et al, 2006;Muraoka-Cook et al, 2006a;Feng et al, 2007), and promotes differentiation (Muraoka-Cook et al, 2006b and apoptosis (Naresh et al, 2006;Vidal et al, 2007). Consistently, many studies suggest that the ErbB4 expression correlates with a good prognosis in breast cancer (Kew et al, 2000;Witton et al, 2003;Barnes et al, 2005;Koutras et al, 2008). However, inconsistent results have also been frequently reported (Tang et al, 1999;Junttila et al, 2005;Maatta et al, 2006;Zhu et al, 2006).…”