title: Low Concordance between Gene Expression Signatures in ER Positive HER2 Negative Breast Carcinoma Could Impair Their Clinical Application.
abstract: BACKGROUND
  Numerous prognostic gene expression signatures have been recently described. Among the signatures there is variation in the constituent genes that are utilized. We aim to evaluate prognostic concordance among eight gene expression signatures, on a large dataset of ER positive HER2 negative breast cancers.
  
  
  METHODS
  We analysed the performance of eight gene expression signatures on six different datasets of ER+ HER2- breast cancers. Survival analyses were performed using the Kaplan-Meier estimate of survival function. We assessed discrimination and concordance between the 8 signatures on survival and recurrence rates The Nottingham Prognostic Index (NPI) was used to to stratify the risk of recurrence/death.
  
  
  RESULTS
  The discrimination ability of the whole signatures, showed fair discrimination performances, with AUC ranging from 0.64 (95%CI 0.55-0.73 for the 76-genes signatures, to 0.72 (95%CI 0.64-0.8) for the Molecular Prognosis Index T17. Low concordance was found in predicting events in the intermediate and high-risk group, as defined by the NPI. Low risk group was the only subgroup with a good signatures concordance.
  
  
  CONCLUSIONS
  Genomic signatures may be a good option to predict prognosis as most of them perform well at the population level. They exhibit, however, a high degree of discordance in the intermediate and high-risk groups. The major benefit that we could expect from gene expression signatures is the standardization of proliferation assessment.
authors.affiliation: Institut Curie, Department of Surgery, Paris, France.|Hopital Tenon, Department of Gynaecologic Surgery, Paris, France.
authors.forename: Enora
authors.initials: E
authors.lastname: Laas
authors.affiliation: Institut Curie, Department of Surgery, Paris, France.|Craigavon Area Hospital Breast Unit, Portadown Northern Ireland, BT63 5QQ.
authors.forename: Peter
authors.initials: P
authors.lastname: Mallon
authors.affiliation: Institut Curie, Department of Medical Oncology, Paris, France.|Centre du Cancer, Cliniques universitaires Saint-Luc, Université catholique de Louvain, B-1200 Brussels, Belgium.
authors.forename: Francois P
authors.initials: FP
authors.lastname: Duhoux
authors.affiliation: Institut Curie, Department of Surgery, Paris, France.
authors.forename: Amina
authors.initials: A
authors.lastname: Hamidouche
authors.affiliation: Institut Curie, Department of Surgery, Paris, France.
authors.forename: Roman
authors.initials: R
authors.lastname: Rouzier
authors.affiliation: Institut Curie, Department of Surgery, Paris, France.|Hopital Tenon, Department of Gynaecologic Surgery, Paris, France.|Institut Curie, Department of Medical Oncology, Paris, France.|Centre du Cancer, Cliniques universitaires Saint-Luc, Université catholique de Louvain, B-1200 Brussels, Belgium.|Institut Curie, Translational Research Department, Residual Tumor and Response to Treatment, RT2Lab, Paris, France.|Institut Curie, UMR932, Immunity and Cancer, Paris, France.
authors.forename: Fabien
authors.initials: F
authors.lastname: Reyal
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality* / Q000473:pathology; D016000:Cluster Analysis; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D060787:Neoplasm Grading; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D011960:Receptors, Estrogen / Q000235:genetics*; D015203:Reproducibility of Results; D059467:Transcriptome
chemical_list: D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen