title: 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=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.
authors.affiliation: 1] Department of Pathology, Seoul National University College of Medicine, Seoul, Korea [2] Department of Pathology, Gangnam Severance Hospital, Seoul, Korea.
authors.forename: Heae Surng
authors.initials: HS
authors.lastname: Park
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Min Hye
authors.initials: MH
authors.lastname: Jang
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea.
authors.forename: Eun Joo
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea.
authors.forename: Hyun Jeong
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Asan Medical Center, Seoul, Korea.
authors.forename: Hee Jin
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Breast Cancer Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea.
authors.forename: Yu Jung
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Breast Cancer Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea.
authors.forename: Jee Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Breast Cancer Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea.
authors.forename: Eunyoung
authors.initials: E
authors.lastname: Kang
authors.affiliation: Breast Cancer Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea.
authors.forename: Sung-Won
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Breast Cancer Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea.
authors.forename: In Ah
authors.initials: IA
authors.lastname: Kim
authors.affiliation: 1] Department of Pathology, Seoul National University College of Medicine, Seoul, Korea [2] Department of Pathology, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea [3] Breast Cancer Center, Seoul National University Bundang Hospital, Seongnam, Gyeonggi, Korea.
authors.forename: So Yeon
authors.initials: SY
authors.lastname: Park
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D018276:Carcinoma, Medullary / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000378:metabolism*; D005091:Exons / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology; D018773:Genes, erbB-1 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012189:Retrospective Studies; D046888:Tissue Array Analysis; D064726:Triple Negative Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D016159:Tumor Suppressor Protein p53; C512478:EGFR protein, human; D066246:ErbB Receptors