We lack tools to risk-stratify triple-negative breast cancer (TNBC). Our goal was to develop molecular tools to predict disease recurrence. Methylation array analysis was performed on 110 samples treated by locoregional therapy obtained from Institutional cohorts. Discovered marker sets were then tested by Kaplan Meier analyses in a prospectively collected TNBC cohort of 49 samples from the no chemotherapy arms of IBCSG trials VIII and IX, and by logistic regression in a chemotherapy-treated cohort of 121 TNBCs from combined IBCSG trials and Institutional repositories. High methylation was associated with shorter recurrence-free interval in the no chemotherapy arm of the IBCSG studies, as well as in the chemotherapy-treated patients within the combined Institutional and IBCSG chemotherapy cohorts (100 marker panel, P=0.002; 30 marker panel, P=0.05). Chromosome 19 sites were enriched among these loci. In conclusion, our hypermethylation signatures identify increased recurrence risk independent of whether patients receive chemotherapy.
Overall design
Three archival TNBC patient sample sets were analysed: An Institutional NoChemo Discovery set of 110 samples of convenience (49 cases & 61 controls) from collaborating institutional tissue archives; One validation NoChemo set of 49 samples from the IBCSG trialists (15 cases & 34 controls); and one combined Institutional and IBCSG Chemo validation set set of 120 samples (26 cases and 94 controls). Only the institutional datasets are available in this repository - access to IBCSG-derived datasets are contingent upon IBSCG review and approval. To request access to data, contact the IBCSG Statistical Center (stat_center@ibcsg.org).
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