PT  - JOURNAL ARTICLE
AU  - SOFIA LEVVA
AU  - VASSILIKI KOTOULA
AU  - IOANNIS KOSTOPOULOS
AU  - KYRIAKI MANOUSOU
AU  - CHRISTOS PAPADIMITRIOU
AU  - KYRIAKI PAPADOPOULOU
AU  - SOTIRIS LAKIS
AU  - KYRIAKOS KOUKOULIAS
AU  - VASILIOS KARAVASILIS
AU  - GEORGE PENTHEROUDAKIS
AU  - EUFEMIA BALASSI
AU  - FLORA ZAGOURI
AU  - IOANNIS G. KAKLAMANOS
AU  - DIMITRIOS PECTASIDES
AU  - EVANGELIA RAZIS
AU  - GERASIMOS ARAVANTINOS
AU  - PAVLOS PAPAKOSTAS
AU  - DIMITRIOS BAFALOUKOS
AU  - GRIGORIOS RALLIS
AU  - HELEN GOGAS
AU  - GEORGE FOUNTZILAS
TI  - Prognostic Evaluation of Epidermal Growth Factor Receptor (EGFR) Genotype and Phenotype Parameters in Triple-negative Breast Cancers
DP  - 2017 May 01
TA  - Cancer Genomics - Proteomics
PG  - 181--195
VI  - 14
IP  - 3
4099  - http://cgp.iiarjournals.org/content/14/3/181.short
4100  - http://cgp.iiarjournals.org/content/14/3/181.full
SO  - Cancer Genomics Proteomics2017 May 01; 14
AB  - Background: Epidermal growth factor receptor (EGFR) aberrations have been implicated in the pathogenesis of triple-negative breast cancer (TNBC) but their impact on prognosis and, therefore, druggability, remain controversial. Herein, we studied EGFR aberrations at different molecular levels and assessed their prognostic impact in patients with operable TNBC treated with adjuvant anthracycline-based chemotherapy. Materials and Methods: We evaluated the prognostic impact of EGFR gene status by fluorescent in situ hybridization (FISH), EGFR coding mutations by Sanger and next-generation sequencing, relative EGFR messenger RNA (mRNA) levels by qPCR (upper quartile) and EGFR and p53 protein expression by immunohistochemistry (IHC), in 352 centrally-assessed tumors from an equal number of TNBC patients. Results: Approximately 53.5% of the tumors expressed EGFR, 59.3% p53 and 35.9% both EGFR and p53 proteins; 4.1% showed EGFR gene amplification and 4.4% carried EGFR mutations. The latter were located outside the druggable kinase domain region and presented at low frequencies. Amplification and mutations overlapped only in one case of glycogen-rich carcinoma. EGFR and CEN7 copies were higher in tumors from older patients (p=0.002 and p=0.003, respectively). Patients with amplified tumors (n=11) had excellent prognosis (0 relapses and deaths). Upon multivariate analysis, high EGFR copies conferred significantly favorable disease-free survival (HR=0.57, 95% CI 0.36-0.90, Wald's p=0.017) and high CEN7 copies favorable overall survival (HR=0.49, 95% CI=0.29-0.83, Wald's p=0.008). Patients with EGFR−/p53+ and EGFR+/p53− tumors had significantly higher risk for relapse than those with EGFR−/p53− and EGFR+/p53+ tumors (HR=1.73, 95% CI=1.12-2.67, Wald's p=0.013). Conclusion: EGFR gene amplification and mutations are rare in TNBC, the latter of no apparent clinical relevance. Surrogate markers of EGFR-related chromosomal aberrations and combined EGFR/p53 IHC phenotypes appear to be associated with favorable prognosis in patients with operable TNBC receiving conventional adjuvant chemotherapy.