Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster Display session 2

3971 - Unravelling the biological characteristics of MammaPrint extreme risk subgroups

Date

29 Sep 2019

Session

Poster Display session 2

Topics

Tumour Site

Breast Cancer

Presenters

Rajith Bhaskaran

Citation

Annals of Oncology (2019) 30 (suppl_5): v55-v98. 10.1093/annonc/mdz240

Authors

R. Bhaskaran1, C. Griffioen1, D. Wehkamp2, L. Mittempergher1, A.M. Glas3

Author affiliations

  • 1 Research & Development, Agendia Inc., 1066NC - Amsterdam/NL
  • 2 Scientific Computing, Agendia Inc., 1066NC - Amsterdam/NL
  • 3 Product Development, Agendia Inc., 1098 XH - Amsterdam/NL

Resources

Login to get immediate access to this content.

If you do not have an ESMO account, please create one for free.

Abstract 3971

Background

MammaPrint® (MP) is a 70-gene based prognostic assay that stratifies early-stage breast cancer patients into low and high-risk of relapse. Recently, further stratification of the 70-gene risk results identified extreme low and high-risk subgroups with specific clinical outcomes (Delahaye et al. 2017) and treatment response characteristics (Wolf et al. 2017). However, the biological profiles of these extreme MP subgroups are not fully investigated. In this study, we aim to gain more insight into their biological significance using differentially expression genes (DEGs) analysis.

Methods

We selected 400 samples from the whole MP range and defined 4 subgroups (Ultra high [UH], High risk [HR], Low risk [LR], Ultra low [UL]), for which FFPE microarray full-transcriptome data were available at Agendia. DEGs analysis was performed with limma and subsequent pathway analysis with Enrichr and GOrilla.

Results

Two separate comparative analyses were carried out to unravel biological processes associated with extreme risk subgroups: UL vs. LR and UH vs. HR. We found 101 DEGs (logFC > =0.485 & FDR <0.05) between UL and LR subgroups and 1714 DEGs between UH and HR subgroups. Based on the pathway analysis, our results showed that the UL subgroup was more homogeneous, with enrichment in pathways reflecting low proliferative and metastatic features. This is in line with the favorable long-term outcome characteristic of the UL group. Conversely UH exhibited higher heterogeneity, with the enrichment of more diverse pathways including immune response, cell cycle and proliferation, that could be associated with genomic instability. This would support the recent finding of UH samples being more sensitive to veliparib/carboplatin combination therapy compared to HR samples (Wolf et al. 2017)). Furthermore, clustering approach demonstrated UH and other subgroups as two distinct clusters.

Conclusions

Our preliminary findings give additional insights into the biological processes associated with extreme MP groups, which might open new avenues for therapeutic intervention in breast cancer.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Agendia Inc.

Funding

Agendia Inc.

Disclosure

R. Bhaskaran: Full / Part-time employment: Agendia Inc. C. Griffioen: Full / Part-time employment: Agendia Inc. D. Wehkamp: Full / Part-time employment: Agendia Inc. L. Mittempergher: Full / Part-time employment: Agendia Inc. A.M. Glas: Full / Part-time employment: Agendia Inc.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings
  • Necessary cookies enable core functionality. The website cannot function properly without these cookies, and you can only disable them by changing your browser preferences.