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.
Resources from the same session
2686 - Clinicopathological characteristics, survival and prognostic factors of breast cancer-related microangiopathic haemolytic anemia: a multicenter study
Presenter: Marion Alhenc Gelas
Session: Poster Display session 2
Resources:
Abstract
1565 - Metabolic tumor volume by 18F-FDG PET/CT is an independent prognostic factor in metastatic breast cancer
Presenter: Heekyung Ahn
Session: Poster Display session 2
Resources:
Abstract
4498 - Patient Preferences for breast cancer treatments: A Discrete Choice Experiment from four European countries
Presenter: Thomais Konstantopoulou
Session: Poster Display session 2
Resources:
Abstract
1423 - Palbociclib plus fulvestrant as second- or later-line therapy for patients with locally advanced, inoperable or metastatic HR+/HER2- breast cancer in Germany: Interim results of the INGE-B phase 2 study
Presenter: Diana Lüftner
Session: Poster Display session 2
Resources:
Abstract
2284 - Ventriculoperitoneal Shunt for CNS Metastasis in Breast Cancer: Clinical Outcomes Based on Intrinsic Subtype
Presenter: Hee Kyung Kim
Session: Poster Display session 2
Resources:
Abstract
4598 - Administration of chemotherapy for metastatic breast cancer near the end of life: a population registry study
Presenter: Luisa Edman Kessler
Session: Poster Display session 2
Resources:
Abstract
5706 - Prognostic value of histological growth pattern in patients operated for breast cancer liver metastases
Presenter: Ali Bohlok
Session: Poster Display session 2
Resources:
Abstract
1697 - Illness perceptions, quality of life and mood in metastatic breast cancer patients
Presenter: Isabel Domingues
Session: Poster Display session 2
Resources:
Abstract
1935 - Multidisciplinary Treatments Increases Overall Survival in Patients with Newly Diagnosed Stage IV Breast Cancer:An Analysis of 2010–2014 SEER Data
Presenter: Jian Zhang
Session: Poster Display session 2
Resources:
Abstract
3875 - Correlation of radiotherapy with the prognosis of elderly patients with hormone receptor-positive breast cancer according to immunohistochemical subtyping
Presenter: Jin Zhang
Session: Poster Display session 2
Resources:
Abstract