Abstract 220P
Background
MammaPrint® (MP) is a 70-gene based assay that stratifies early-stage breast cancer patients into low and high-risk of relapse. Blueprint® (BP) is a 80-gene based assay that stratifies breast cancer patients in 3 molecular subtypes (Basal, Luminal and HER2). Previously, we showed that the MP genes reflect the six hallmarks of cancer (HoC) as defined by Hanahan and Weinberg (Tian et al 2011). Later, these were extended to ten HoC (Hanahan et al. 2011). In this study we annotated the MP 70- and BP 80-genes with respect to the ten HoC. In addition, further stratification of the MP risk results identified ultra low- and high-risk subgroups with specific prognostic (Delahaye et al, 2017, Esserman et al, 2017) and predictive outcomes (Wolf et al, 2017). To gain more insight into their biological significance we related gene expression profiles of the ultra low/high MP subgroups to the ten HoC per BP subtype.
Methods
To associate the MP and BP genes to the hallmarks of cancer we used the Cancer Hallmarks Analytics Tool (CHAT). For expression analysis, we selected full-transcriptome data from 600 FFPE samples that were archived at Agendia. MP subgroups (Ultra high (UH) vs High risk (HR) and Ultra Low (UL) vs Low risk (LR)) from each BP subtype were compared to further understand the biological characteristics by use of Limma and subsequent pathway analysis with GSEA.
Results
MP and BP gene functions reflected all ten HoC. Majority of MP and BP genes were associated to sustaining proliferative signaling, followed by genome instability and mutation. Based on the gene expression profiles, UL and UH subgroups were enriched, in opposite directions, in pathways reflecting proliferative and metastatic features. Additionally, the UH subgroup was enriched in evading growth suppressors, genome instability, mutation and enabling replicative immortality pathways. Notably, the UH HER2 subgroup was enriched in several immune signaling pathways.
Conclusions
In this study we show that also the extended 10 HoC reflect the MP and BP test. Importantly, our results highlight underlying biological processes of extreme risk MP samples, which might guide relevant treatment decisions as it pertains to the broad spectrum of early breast cancers.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Agendia.
Funding
Has not received any funding.
Disclosure
J.C. Haan, R. Bhaskaran, Mittempergher, E. Lujinovic, W. Audeh, A. Glas: Full/Part-time employment: Agendia. All other authors have declared no conflicts of interest.