title: Prediction of breast cancer survival using clinical and genetic markers by tumor subtypes.
abstract: OBJECTIVE
  To identify the genetic variants associated with breast cancer survival, a genome-wide association study (GWAS) was conducted of Korean breast cancer patients.
  
  
  METHODS
  From the Seoul Breast Cancer Study (SEBCS), 3,226 patients with breast cancer (1,732 in the discovery and 1,494 in the replication set) were included in a two-stage GWAS on disease-free survival (DFS) by tumor subtypes based on hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2). The associations of the re-classified combined prognostic markers through recursive partitioning analysis (RPA) of DFS for breast cancer were assessed with the Cox proportional hazard model. The prognostic predictive values of the clinical and genetic models were evaluated by Harrell's C.
  
  
  RESULTS
  In the two-stage GWAS stratified by tumor subtypes, rs166870 and rs10825036 were consistently associated with DFS in the HR+ HER2- and HR- HER2- breast cancer subtypes, respectively (Prs166870 = 2.88 × 10(-7) and Prs10825036 = 3.54 × 10(-7) in the combined set). When patients were classified by the RPA in each subtype, genetic factors contributed significantly to differentiating the high risk group associated with DFS inbreast cancer, specifically the HR+ HER2- (P discovery=1.18 × 10(-8) and P replication = 2.08 × 10(-5)) and HR- HRE2- subtypes (P discovery = 2.35 × 10(-4) and P replication = 2.60 × 10(-2)). The inclusion of the SNPs tended to improve the performance of the prognostic models consisting of age, TNM stage and tumor subtypes based on ER, PR, and HER2 status.
  
  
  CONCLUSIONS
  Combined prognostic markers that include clinical and genetic factors by tumor subtypes could improve the prediction of survival in breast cancer.
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
authors: Nan
authors: N
authors: Song
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Ji-Yeob
authors: JY
authors: Choi
authors: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea; Division of Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, United States of America.
authors: Hyuna
authors: H
authors: Sung
authors: Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Sujee
authors: S
authors: Jeon
authors: Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea.
authors: Seokang
authors: S
authors: Chung
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Sue K
authors: SK
authors: Park
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors: Wonshik
authors: W
authors: Han
authors: Department of Surgery, University of Ulsan College of Medicine and ASAN Medical Center, Seoul, Korea.
authors: Jong Won
authors: JW
authors: Lee
authors: Division of Cancer Epidemiology and Management, National Cancer Center, Goyang-si, Gyeonggi-do, Korea.
authors: Mi Kyung
authors: MK
authors: Kim
authors: Cardiovascular Research Institute and Cardiovascular Genome Center, Yonsei University Health System, Seoul, Korea.
authors: Ji-Young
authors: JY
authors: Lee
authors: Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Keun-Young
authors: KY
authors: Yoo
authors: Center for Genome Science, Korea National Institute of Health, Osong, Korea.
authors: Bok-Ghee
authors: BG
authors: Han
authors: Department of Surgery, University of Ulsan College of Medicine and ASAN Medical Center, Seoul, Korea.
authors: Sei-Hyun
authors: SH
authors: Ahn
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
authors: Dong-Young
authors: DY
authors: Noh
authors: Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea; Department of Preventive Medicine, Seoul National University College of Medicine, Seoul, Korea.
authors: Daehee
authors: D
authors: Kang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000145:classification / Q000235:genetics / Q000473:pathology*; D016022:Case-Control Studies; D005260:Female; D005819:Genetic Markers; D055106:Genome-Wide Association Study; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D056910:Republic of Korea
chemical_list: D005819:Genetic Markers