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

Abstract

Epidermal growth factor receptor (EGFR) is frequently overexpressed in triple-negative breast cancer and is emerging as a therapeutic target. EGFR gene copy number alteration and mutation are highly variable and scientists have been challenged to define their prognostic significance in triple-negative breast cancer. We examined EGFR protein expression, EGFR gene copy number alteration and mutation of exon 18 to 21 in 151 cases 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. EGFR overexpression 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 4 of 151 cases (3%) and included G719A in exon 18 (n ¼ 1), V786M in exon 20 (n ¼ 1), and L858R in exon 21 (n ¼ 3). One case had two mutations (G719A and L858R). High EGFR copy number, but not EGFR mutation, correlated with EGFR protein overexpression. Intratumoral heterogeneity of EGFR protein overexpression and EGFR copy number alteration was not significant. In survival analyses, high EGFR copy number was found to be an independent prognostic factor for poor disease-free survival in patients with triple-negative breast cancer. Our findings showed that EGFR mutation was a rare event, but high EGFR copy number was relatively frequent and correlated with EGFR overexpression in triple-negative breast cancer. Moreover, high EGFR copy number was associated with poor clinical outcome in triple-negative breast cancer, suggesting that evaluation of EGFR copy number may be useful for predicting outcomes in patients with triple-negative breast cancer and for selecting patients for anti-EGFR-targeted therapy.

Epidermal growth factor receptor protein overexpression and gene amplification are associated with aggressive biological behaviors of esophageal squamous cell carcinoma

“…EGFR overexpression is mostly due to EGFR gene amplification or mutations, with the latter occurring frequently in EGFR exons 18-21, which encode the tyrosine kinase section of the EGFR protein. Previous studies have demonstrated an association between EGFR alterations and aggressive biological behaviors (e.g., tumor cell dedifferentiation, advanced tumor stage or cancer metastasis) of different human cancers of epithelial origin, including head and neck, breast, colon, stomach and lung cancer (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) (20)(21)(22). EGFR amplification and protein overexpression have been reported in ESCC and premalignant lesions (3,9,19) and the overexpression of EGFR was found to be significantly associated with the depth of invasion of the tumor (9).…”

Clinicopathological and Immunohistochemical Features of Triple Negative Breast Cancer

“…In addition, its overexpression is ra-Advances in Breast Cancer Research lated with the poor disease-free survival of TNBC [14]. Moreover, recent studies have shown that cetuximab as a EGFR target drug can increase the total remission rate of TNBC [15].…”

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“…The eleven lines tested included triple negative and Her2 positive breast cancers of grade 2 or higher, and we observed that Llgl1 loss was associated with increased EGFR expression. EGFR expression, high CD44 expression, and migration have all been linked to decreased patient survival [39][40][41][42][43][44]. We therefore analyzed a publicly available GEO data set (GSE3494) with 236 breast cancer patients for Llgl1 expression and long term survival ( Figure 7E).…”