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. 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.
Document type :
Journal articles
Complete list of metadatas

Cited literature [42 references]  Display  Hide  Download
Contributor : Archive Ouverte Prodinra <>
Submitted on : Thursday, October 22, 2015 - 8:20:02 PM
Last modification on : Thursday, August 29, 2019 - 1:10:55 AM
Long-term archiving on : Friday, April 28, 2017 - 6:28:27 AM


Explicit agreement for this submission



Anne Vincent-Salomon, Vanessa Benhamo, Eleonore Gravier, Guillem Rigaill, Nadège Gruel, et al.. Genomic instability : a stronger prognostic marker than proliferation for early stage luminal breast carcinomas. PLoS ONE, Public Library of Science, 2013, 8 (10), ⟨10.1371/journal.pone.0076496⟩. ⟨hal-01219550⟩



Record views


Files downloads