title: Prognostic value of ERBB4 expression in patients with triple negative breast cancer.
abstract: BACKGROUND
  Triple-negative breast cancer (TNBC) is known for aggressive biologic features and poor prognosis. Epidermal growth factor receptor (EGFR) overexpression in TNBC indicates poor prognosis. However, there is no previous study of the relationship between expression of the entire human epidermal growth factor receptor (HER) family genes and patient prognosis in TNBC. Accordingly, we investigated the expression profiles of HER family genes in patients with TNBC to determine the prognostic value and clinical implications of HER family expression.
  
  
  METHODS
  We used the nCounter expression assay (NanoString®) to measure the expression of EGFR, erb-B2 receptor tyrosine kinase 2 (ERBB2), ERBB3, ERBB4, and estrogen receptor 1 (ESR1) genes using mRNA extracted from paraffin-embedded tumor tissues from 203 patients diagnosed with TNBC. Our data were validated using a separate cohort of 84 TNBC patients.
  
  
  RESULTS
  A total of 203 TNBC patients who received adjuvant chemotherapy after curative surgery from 2000 to 2004 formed the training set. The 84 TNBC patients in the validation consort were selected from breast cancer patients who received curative surgery since 2005 to 2010. Analysis of the expression profiles of the HER family genes in TNBC tissue specimens revealed that increased expression of ERBB4 was associated with poor prognosis according to survival analysis (5-year distant relapse free survival [5Y DRFS], low vs. high expression [cut-off: median]: 90.1% vs. 80.2%; p = 0.022). This trend was also observed in the validation set of TNBC patients (5Y DRFS, low vs. high: 69.4% vs. 44.7%; p = 0.053). In a multivariate Cox regression model, ERBB4 expression was identified as a indicator of long-term prognosis in patients with TNBC.
  
  
  CONCLUSIONS
  The expression profile of ERBB4, a member of the HER family, might serve as a prognostic marker in patients with TNBC.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Korea. jyeon25.kim@samsung.com.
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Korea. haehyun.jung@sbri.co.kr.
authors.forename: Hae Hyun
authors.initials: HH
authors.lastname: Jung
authors.affiliation: Cancer of Companion Diagnostics, Innovative Cancer Medicine Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Korea. ingu.do@samsung.com.
authors.forename: In-Gu
authors.initials: IG
authors.lastname: Do
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Korea. sooyoun.bae@samsung.com.
authors.forename: SooYoun
authors.initials: S
authors.lastname: Bae
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Korea. sekyung.lee@samsung.com.
authors.forename: Se Kyung
authors.initials: SK
authors.lastname: Lee
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Korea. seokwon1.kim@samsung.com.
authors.forename: Seok Won
authors.initials: SW
authors.lastname: Kim
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Korea. jeongeon.lee@samsung.com.
authors.forename: Jeong Eon
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Korea. seokjin.nam@samsung.com.
authors.forename: Seok Jin
authors.initials: SJ
authors.lastname: Nam
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Korea. jinseok.ahn@samsung.com.
authors.forename: Jin Seok
authors.initials: JS
authors.lastname: Ahn
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Korea. yhparkhmo@skku.edu.|Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Korea. yhparkhmo@skku.edu.
authors.forename: Yeon Hee
authors.initials: YH
authors.lastname: Park
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Korea. imyh00@skku.edu.|Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 135-710, Korea. imyh00@skku.edu.
authors.forename: Young-Hyuck
authors.initials: YH
authors.lastname: Im
mesh_terms: D000328:Adult; D014408:Biomarkers, Tumor / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D020893:Receptor, ErbB-3 / Q000235:genetics; D066247:Receptor, ErbB-4 / Q000235:genetics*; D016019:Survival Analysis; D064726:Triple Negative Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; D066246:ErbB Receptors; D047628:Estrogen Receptor alpha; D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; C506487:ESR1 protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C581292:ERBB3 protein, human; C587689:ERBB4 protein, human