PLoS ONE (Jan 2013)

Genomic instability: a stronger prognostic marker than proliferation for early stage luminal breast carcinomas.

  • Anne Vincent-Salomon,
  • Vanessa Benhamo,
  • Eléonore Gravier,
  • Guillem Rigaill,
  • Nadège Gruel,
  • Stéphane Robin,
  • Yann de Rycke,
  • Odette Mariani,
  • Gaëlle Pierron,
  • David Gentien,
  • Fabien Reyal,
  • Paul Cottu,
  • Alain Fourquet,
  • Roman Rouzier,
  • Xavier Sastre-Garau,
  • Olivier Delattre

DOI
https://doi.org/10.1371/journal.pone.0076496
Journal volume & issue
Vol. 8, no. 10
p. e76496

Abstract

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BACKGROUND:The accurate prognosis definition to tailor treatment for early luminal invasive breast carcinoma patients remains challenging. MATERIALS AND 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 . CONCLUSION:Genomic instability, defined herein as a high number of chromosomal breakpoints, in early stage luminal breast carcinoma is a stronger prognostic marker than proliferation.