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

Heae Surng Park, Min Hye Jang, Eun Joo Kim, Hyun Jeong Kim, Hee Jin Lee, Yu Jung Kim, Jee Hyun Kim, Eunyoung Kang, Sung Won Kim, In Ah Kim, So Yeon Park

Research output: Contribution to journalArticle

104 Citations (Scopus)

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=1), V786M in exon 20 (n=1), and L858R in exon 21 (n=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.

Original languageEnglish
Pages (from-to)1212-1222
Number of pages11
JournalModern Pathology
Volume27
Issue number9
DOIs
StatePublished - 1 Sep 2014

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Triple Negative Breast Neoplasms
erbB-1 Genes
Gene Dosage
Epidermal Growth Factor Receptor
Mutation
Exons
Proteins
Gene Amplification

Keywords

  • Breast carcinoma
  • Copy number gain
  • EGFR
  • Fluorescence in situ hybridization
  • Mutation

Cite this

Park, Heae Surng ; Jang, Min Hye ; Kim, Eun Joo ; Kim, Hyun Jeong ; Lee, Hee Jin ; Kim, Yu Jung ; Kim, Jee Hyun ; Kang, Eunyoung ; Kim, Sung Won ; Kim, In Ah ; Park, So Yeon. / High EGFR gene copy number predicts poor outcome in triple-negative breast cancer. In: Modern Pathology. 2014 ; Vol. 27, No. 9. pp. 1212-1222.
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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=1), V786M in exon 20 (n=1), and L858R in exon 21 (n=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.",
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High EGFR gene copy number predicts poor outcome in triple-negative breast cancer. / Park, Heae Surng; Jang, Min Hye; Kim, Eun Joo; Kim, Hyun Jeong; Lee, Hee Jin; Kim, Yu Jung; Kim, Jee Hyun; Kang, Eunyoung; Kim, Sung Won; Kim, In Ah; Park, So Yeon.

In: Modern Pathology, Vol. 27, No. 9, 01.09.2014, p. 1212-1222.

Research output: Contribution to journalArticle

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AU - Park, Heae Surng

AU - Jang, Min Hye

AU - Kim, Eun Joo

AU - Kim, Hyun Jeong

AU - Lee, Hee Jin

AU - Kim, Yu Jung

AU - Kim, Jee Hyun

AU - Kang, Eunyoung

AU - Kim, Sung Won

AU - Kim, In Ah

AU - Park, So Yeon

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AB - 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=1), V786M in exon 20 (n=1), and L858R in exon 21 (n=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.

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