Abstract
BackgroundThe accurate prognosis definition to tailor treatment for early luminal invasive breast carcinoma patients remains challenging.Materials and MethodsTwo 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.ResultsIn 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 .ConclusionGenomic instability, defined herein as a high number of chromosomal breakpoints, in early stage luminal breast carcinoma is a stronger prognostic marker than proliferation.
Highlights
A major challenge of breast cancer treatment is to accurately identify patients in whom adjuvant therapy can be safely avoided [1]
While luminal carcinoma patients display various outcomes according to their tumor proliferation rate and clinical stage, they harbor a constellation of driver gene mutations and chromosomal alterations [5,6,7,8,9]
We focused our analysis on early luminal HER2-negative node-negative breast cancers, i.e. in the population of patients in whom prognosis assessment remains challenging, in whom treatment must be adapted to tumor biology and decreased as far as possible to minimize the side effects of chemotherapy
Summary
A major challenge of breast cancer treatment is to accurately identify patients in whom adjuvant therapy can be safely avoided [1]. 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. Conclusion: Genomic instability, defined as a high number of chromosomal breakpoints, in early stage luminal breast carcinoma is a stronger prognostic marker than proliferation
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