title: Genomic instability: a stronger prognostic marker than proliferation for early stage luminal breast carcinomas.
abstract: BACKGROUND
  The accurate prognosis definition to tailor treatment for early luminal invasive breast carcinoma patients remains challenging.
  
  
  METHODS
  Two hundred fourteen early luminal breast carcinomas were genotyped with single nucleotide polymorphisms (SNPs) array to determine the number of chromosomal breakpoints as a marker of genomic instability. Proliferation was assessed by KI67 (immunohistochemistry) and genomic grade index (transcriptomic analysis). IHC3 (IHC4 score for HER2 negative tumors) was also determined.
  
  
  RESULTS
  In the training set (109 cases), the optimal cut-off was 34 breakpoints with a specificity of 0.94 and a sensitivity of 0.57 (Area under the curve (AUC): 0.81[0.71; 0.91]). In the validation set (105 cases), the outcome of patients with > 34 breakpoints (11 events / 22 patients) was poorer (logrank test p < 0.001; Relative Risk (RR): 3.7 [1.73; 7.92]), than that of patients with < 34 breakpoints (19 events / 83 patients).Whereas genomic grade and KI67 had a significant prognostic value in univariate analysis in contrast to IHC3 that failed to have a statistical significant prognostic value in this series, the number of breakpoints remained the only significant parameter predictive of outcome (RR: 3.47, Confidence Interval (CI [1.29; 9.31], p = 0.014)) in multivariate analysis .
  
  
  CONCLUSIONS
  Genomic instability, defined herein as a high number of chromosomal breakpoints, in early stage luminal breast carcinoma is a stronger prognostic marker than proliferation.
authors.affiliation: Department of Tumor Biology, Institut Curie, Paris, France ; INSERM U830, Institut Curie, Paris, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Vincent-Salomon
authors.forename: Vanessa
authors.initials: V
authors.lastname: Benhamo
authors.forename: Eléonore
authors.initials: E
authors.lastname: Gravier
authors.forename: Guillem
authors.initials: G
authors.lastname: Rigaill
authors.forename: Nadège
authors.initials: N
authors.lastname: Gruel
authors.forename: Stéphane
authors.initials: S
authors.lastname: Robin
authors.forename: Yann
authors.initials: Y
authors.lastname: de Rycke
authors.forename: Odette
authors.initials: O
authors.lastname: Mariani
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Pierron
authors.forename: David
authors.initials: D
authors.lastname: Gentien
authors.forename: Fabien
authors.initials: F
authors.lastname: Reyal
authors.forename: Paul
authors.initials: P
authors.lastname: Cottu
authors.forename: Alain
authors.initials: A
authors.lastname: Fourquet
authors.forename: Roman
authors.initials: R
authors.lastname: Rouzier
authors.forename: Xavier
authors.initials: X
authors.lastname: Sastre-Garau
authors.forename: Olivier
authors.initials: O
authors.lastname: Delattre
mesh_terms: D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D056905:Chromosome Breakpoints; D019295:Computational Biology; D018572:Disease-Free Survival; D005260:Female; D042822:Genomic Instability; D060005:Genotyping Techniques; D006801:Humans; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results
chemical_list: D019394:Ki-67 Antigen