Abstract P4-09-04: Robust 7-gene signature for recurrence prognosis of breast cancer validated in formalin-fixed paraffin-embedded samples

Abstract

BACKGROUND: Breast cancer (BC) is a heterogeneous disease with diverse biological-molecular characteristics and clinical behaviors. Traditionally, prediction of recurrence in patients recently diagnosed is a big challenge for oncologists. In the last decade, advances in gene expression profiling technologies have improved the genetic knowledge of breast cancer by reporting several prognostic gene-signatures. However, there is still a need for covering the molecular heterogeneity of this cancer. Integration of public microarray data could be used to identify better and robust predictive gene-signatures. The aim of this study was to investigate prognostic genes that might function as biomarkers to differentiate among all heterogeneous BC patients, into those with high, medium or low recurrence risk. METHODS: We collected nine public datasets, 1574 BC patients with median follow-up time of 10 years. The data were split into train-test, 50% each. Train was subject to univariate and multivariate analysis to generate a signature, which was validated in the test data. Seven genes were identified with high accuracy for recurrence prediction. This signature was validated in 40 formalin-fixed paraffin-embedded (FFPE) Mexican BC tissues with clinical follow up of 3 to 13 years by quantitative RT-PCR assays. RESULTS: We identified a 7-gene signature which showed an accuracy prediction measured by concordance index of 65.62% and Log-rank test p-value: 1 x 10-15. The validation of the gene-signature level expression in 40 FFPE samples in Kaplan Meier analysis showed prediction significance by concordance index of 65.25% and Log-Rank p-value: 0.0005. CONCLUSIONS: This 7-gene signature may provide a powerful tool to guide the adequate treatment protocols in early-diagnosed breast cancer patients. Citation Format: Chacolla RJ, Trevino VM, Scott SP, Guzman EA, Cardona S. Robust 7-gene signature for recurrence prognosis of breast cancer validated in formalin-fixed paraffin-embedded samples. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-09-04.