title: Statistical methods applied to omics data: predicting response to neoadjuvant therapy in breast cancer.
abstract: OBJECTIVE
  Omics technologies have become an essential part of clinical trials in oncology to provide a better understanding of molecular mechanisms and to unveil therapeutic targets. Standard statistical methods often fail in the high-dimensional setting. Therefore, an adequate modelling of the omics data is needed in order to identify 'target' genes of interest.
  
  
  RESULTS
  Several genes or gene signatures have been identified to predict the response to neoadjuvant therapies in breast cancer trials. We first reviewed statistical methods used to identify genes in 13 recent publications. Most of these studies had a small sample size (median: 42 patients) and were nonrandomized. We then focused on some popular methods - especially the so-called penalized methods used by three of the reviewed articles - and on the more recent methods proposed to predict causal estimates from observational data. We finally illustrated these methods in a nonrandomized neoadjuvant phase II trial of letrozole in estrogen receptor-positive breast cancer patients.
  
  
  CONCLUSIONS
  The review highlighted small sample sizes, few randomized trials and a large panel of statistical methods used in this setting. In our illustrated neoadjuvant example, causal inference methods did not outperform the penalized methods.
authors.affiliation: aService biostatistique et épidémiologie, Gustave-Roussy, Villejuif, bUniversity Paris-Sud, Le Kremlin-Bicêtre cDépartement de médecine, Pathologie Mammaire, Gustave-Roussy, Villejuif, France.
authors.forename: Nils
authors.initials: N
authors.lastname: Ternès
authors.forename: Monica
authors.initials: M
authors.lastname: Arnedos
authors.forename: Serge
authors.initials: S
authors.lastname: Koscielny
authors.forename: Stefan
authors.initials: S
authors.lastname: Michiels
authors.forename: Emilie
authors.initials: E
authors.lastname: Lanoy
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D020360:Neoadjuvant Therapy