title: Prognostic and predictive values of EGFR overexpression and EGFR copy number alteration in HER2-positive breast cancer.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) is overexpressed in a subset of human epidermal growth factor receptor 2 (HER2)-positive breast cancers, and coexpression of HER2 and EGFR has been reported to be associated with poor clinical outcome. Moreover, interaction between HER2 and EGFR has been suggested to be a possible basis for trastuzumab resistance.
  
  
  METHODS
  We analysed the clinical significance of EGFR overexpression and EGFR gene copy number alterations in 242 HER2-positive primary breast cancers. In addition, we examined the correlations between EGFR overexpression, trastuzumab response and clinical outcome in 447 primary, and 112 metastatic HER2-positive breast cancer patients treated by trastuzumab.
  
  
  RESULTS
  Of the 242 primary cases, the level of EGFR overexpression was 2+ in 12.7% and 3+ in 11.8%. High EGFR gene copy number was detected in 10.3%. Epidermal growth factor receptor overexpression was associated with hormone receptor negativity and high Ki-67 proliferation index. In survival analyses, EGFR overexpression, but not high EGFR copy number, was associated with poor disease-free survival in all patients, and in the subgroup not receiving adjuvant trastuzumab. In 447 HER2-positive primary breast cancer patients treated with adjuvant trastuzumab, EGFR overexpression was also an independent poor prognostic factor. However, EGFR overexpression was not associated with trastuzumab response, progression-free survival or overall survival in the metastatic setting.
  
  
  CONCLUSIONS
  Epidermal growth factor receptor overexpression, but not high EGFR copy number, is a poor prognostic factor in HER2-positive primary breast cancer. Epidermal growth factor receptor overexpression is a predictive factor for trastuzumab response in HER2-positive primary breast cancer, but not in metastatic breast cancer.
authors.affiliation: 1] Department of Pathology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi 463-707, Korea [2] Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-746, Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi 463-707, Korea.
authors.forename: A N
authors.initials: AN
authors.lastname: Seo
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi 463-707, Korea.
authors.forename: E J
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi 463-707, Korea.
authors.forename: M H
authors.initials: MH
authors.lastname: Jang
authors.affiliation: 1] Department of Medical Oncology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi 463-707, Korea [2] Department of Medical Oncology, Seoul National University College of Medicine, 28 Yeongon-dong, Jongno-gu, Seoul 110-799, Korea.
authors.forename: Y J
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: 1] Department of Medical Oncology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi 463-707, Korea [2] Department of Medical Oncology, Seoul National University College of Medicine, 28 Yeongon-dong, Jongno-gu, Seoul 110-799, Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
authors.affiliation: 1] Department of Surgery, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi 463-707, Korea [2] Department of Surgery, Seoul National University College of Medicine, 28 Yeongon-dong, Jongno-gu, Seoul 110-799, Korea.
authors.forename: S-W
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, 28 Yeongon-dong, Jongno-gu, Seoul 110-799, Korea.
authors.forename: H S
authors.initials: HS
authors.lastname: Ryu
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, 28 Yeongon-dong, Jongno-gu, Seoul 110-799, Korea.
authors.forename: I A
authors.initials: IA
authors.lastname: Park
authors.affiliation: Department of Medical Oncology, Seoul National University College of Medicine, 28 Yeongon-dong, Jongno-gu, Seoul 110-799, Korea.
authors.forename: S-A
authors.initials: SA
authors.lastname: Im
authors.affiliation: Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-746, Korea.
authors.forename: G
authors.initials: G
authors.lastname: Gong
authors.affiliation: Department of Medical Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-746, Korea.
authors.forename: K H
authors.initials: KH
authors.lastname: Jung
authors.affiliation: Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul 138-746, Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Kim
authors.affiliation: 1] Department of Pathology, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam-si, Gyeonggi 463-707, Korea [2] Department of Pathology, Seoul National University College of Medicine, 28 Yeongon-dong, Jongno-gu, Seoul 110-799, Korea.
authors.forename: S Y
authors.initials: SY
authors.lastname: Park
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D066246:ErbB Receptors / Q000096:biosynthesis* / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D018628:Gene Dosage; D006801:Humans; D011237:Predictive Value of Tests; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis*; D012189:Retrospective Studies; D016019:Survival Analysis; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C512478:EGFR protein, human; C508053:ERBB2 protein, human