High EGFR gene copy number predicts poor outcome in triple-negative breast cancer

Epidermal growth factor receptor (EGFR) is frequently overexpressed in triple-negative breast cancer and isemerging as a therapeutic target. EGFR gene copy number alteration and mutation are highly variable andscientists have been challenged to define their prognostic significance in triple-negative breast cancer. Weexamined EGFR protein expression, EGFR gene copy number alteration and mutation of exon 18 to 21 in 151cases of triple-negative breast cancer and correlated these findings with clinical outcomes. In addition,intratumoral agreement of EGFR protein overexpression and gene copy number alteration was evaluated. EGFRoverexpression was found in 97 of 151 cases (64%) and high EGFR gene copy number was detected in 50 cases(33%), including 3 gene amplification (2%) and 47 high polysomy (31%). Five EGFR mutations were detected in 4of 151 cases (3%) and included G719A in exon 18 (n¼1), V786M in exon 20 (n¼1), and L858R in exon 21 (n¼3).One case had two mutations (G719A and L858R). High EGFR copy number, but not EGFR mutation, correlatedwith EGFR protein overexpression. Intratumoral heterogeneity of EGFR protein overexpression and EGFR copynumber alteration was not significant. In survival analyses, high EGFR copy number was found to be anindependent prognostic factor for poor disease-free survival in patients with triple-negative breast cancer. Ourfindings showed that EGFR mutation was a rare event, but high EGFR copy number was relatively frequent andcorrelated with EGFR overexpression in triple-negative breast cancer. Moreover, high EGFR copy number wasassociated with poor clinical outcome in triple-negative breast cancer, suggesting that evaluation of EGFR copynumber may be useful for predicting outcomes in patients with triple-negative breast cancer and for selectingpatients for anti-EGFR-targeted therapy.Modern Pathology advance online publication, 10 January 2014; doi:10.1038/modpathol.2013.251Keywords: breast carcinoma; copy number gain; EGFR; fluorescence in situ hybridization; mutation