A High Number of Chromosomal Breakpoints Identifies Poor Prognosis N0 Luminal HER2 Negative Early Invasive Breast Carcinomas Better Than Proliferation
Anne Vincent-Salomon, Vanessa Benhamo, Eleonore Gravier, Yann De Rycke, Odette Mariani, Fabien Reyal, Paul Cottu, Alain Fourquet, Xavier Sastre, Olivier Delattre. Institut Curie, Paris, France; INSERM U830, Paris, France
Background: Our aim was to validate a DNA genomic complexity signature in early luminal ERBB2-ve node negative invasive carcinomas.
Design: A training set of 214 cases (30 cases with a metastatic event within less than 4 years; 79 controls with no metastastic event at 5 years) and a validation set composed of 105 consecutive patients (30 relapses and 8 metastatic events) were genotyped with SNPs array. Proliferation was assessed in the validation series both with Ki67 (immunohistochemistry) and the genomic grade index (transcriptomic analysis).
Results: In the training set, the threshold (Younden index) was 34 breakpoints with a sensitivity of 0.57 and a specificity of 0.94 (AUC: 0.81[0.71;0.91]. In the validation set, the outcome of patients with > 34 breakpoints was poorer (19 events/83 patients) than that of patients with < 34 breakpoints (11 events/22 patients) with a median time to progression of 108 months (logrank test p<0.001; RR: 3.7 [1.73; 7.92]). In multivariate analysis, the number of breakpoints remained the only significant parameter for prediction of outcome (RR: 3.12, CI[1.33; 7.31], p= 0.009). Ki67 and the Genomic Grade Index were not significant in multivariate analysis but were correlated with the number of breakpoints.
Conclusions: Here, we demonstrated that patients with small N0 luminal ERBB2-ve invasive carcinomas harbored a shorter disease and metastatic free intervals when > 34 breakpoints were identified on genomic profiles assessed by SNPs. This genomic complexity signature in this series of early luminal ERBB2-ve carcinomas does better than proliferation to determine the outcome.
Tuesday, March 5, 2013 9:00 AM
Proffered Papers: Section B, Tuesday Morning