title: Concordance among gene expression-based predictors for ER-positive breast cancer treated with adjuvant tamoxifen.
abstract: BACKGROUND
  ER-positive (ER+) breast cancer includes all of the intrinsic molecular subtypes, although the luminal A and B subtypes predominate. In this study, we evaluated the ability of six clinically relevant genomic signatures to predict relapse in patients with ER+ tumors treated with adjuvant tamoxifen only.
  
  
  METHODS
  Four microarray datasets were combined and research-based versions of PAM50 intrinsic subtyping and risk of relapse (PAM50-ROR) score, 21-gene recurrence score (OncotypeDX), Mammaprint, Rotterdam 76 gene, index of sensitivity to endocrine therapy (SET) and an estrogen-induced gene set were evaluated. Distant relapse-free survival (DRFS) was estimated by Kaplan-Meier and log-rank tests, and multivariable analyses were done using Cox regression analysis. Harrell's C-index was also used to estimate performance.
  
  
  RESULTS
  All signatures were prognostic in patients with ER+ node-negative tumors, whereas most were prognostic in ER+ node-positive disease. Among the signatures evaluated, PAM50-ROR, OncotypeDX, Mammaprint and SET were consistently found to be independent predictors of relapse. A combination of all signatures significantly increased the performance prediction. Importantly, low-risk tumors (>90% DRFS at 8.5 years) were identified by the majority of signatures only within node-negative disease, and these tumors were mostly luminal A (78%-100%).
  
  
  CONCLUSIONS
  Most established genomic signatures were successful in outcome predictions in ER+ breast cancer and provided statistically independent information. From a clinical perspective, multiple signatures combined together most accurately predicted outcome, but a common finding was that each signature identified a subset of luminal A patients with node-negative disease who might be considered suitable candidates for adjuvant endocrine therapy alone.
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, USA; Department of Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: A
authors.initials: A
authors.lastname: Prat
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Parker
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, USA.
authors.forename: C
authors.initials: C
authors.lastname: Fan
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, USA.
authors.forename: M C U
authors.initials: MCU
authors.lastname: Cheang
authors.affiliation: Department of Cancer Biology, Comprehensive Cancer Center, Wake Forest School of Medicine, Winston Salem, USA.
authors.forename: L D
authors.initials: LD
authors.lastname: Miller
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet & Cancer Center Karolinska, Stockholm, Sweden; Department of Medical Oncology, Paterson Institute, Christie Hospital and Manchester University, Manchester, UK.
authors.forename: J
authors.initials: J
authors.lastname: Bergh
authors.affiliation: British Columbia Cancer Agency, Vancouver, Canada.
authors.forename: S K L
authors.initials: SKL
authors.lastname: Chia
authors.affiliation: Department of Pathology, University of Utah Health Sciences Center, Salt Lake City, USA.
authors.forename: P S
authors.initials: PS
authors.lastname: Bernard
authors.affiliation: British Columbia Cancer Agency, Vancouver, Canada; Department of Pathology, University of British Columbia, Vancouver, Canada.
authors.forename: T O
authors.initials: TO
authors.lastname: Nielsen
authors.affiliation: Department of Medicine, Division of Oncology, Siteman Cancer Center at Washington University, St. Louis.
authors.forename: M J
authors.initials: MJ
authors.lastname: Ellis
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, USA; Deparment of Medicine, Division of Hematology and Oncology, University of North Carolina, Chapel Hill.
authors.forename: L A
authors.initials: LA
authors.lastname: Carey
authors.affiliation: Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, USA; Departments of Genetics; Pathology & Laboratory Medicine, University of North Carolina, Chapel Hill, USA. Electronic address: cperou@med.unc.edu.
authors.forename: C M
authors.initials: CM
authors.lastname: Perou
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D023281:Genomics; D006801:Humans; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism*; D013629:Tamoxifen / Q000627:therapeutic use*
chemical_list: D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D013629:Tamoxifen