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Poster session 01

119P - Characterisation of distinct subgroups of BRCA1-like triple-negative breast cancers with multiomics data analysis

Date

10 Sep 2022

Session

Poster session 01

Topics

Cytotoxic Therapy

Tumour Site

Breast Cancer

Presenters

Terry Wing Sheung Chan

Citation

Annals of Oncology (2022) 33 (suppl_7): S27-S54. 10.1016/annonc/annonc1037

Authors

T.W.S. Chan1, M. Opdam1, P. Schouten1, L. De Boo1, F.S. Hilbers1, S.C. Linn2, R.X. de Menezes3

Author affiliations

  • 1 Dept Of Molecular Oncology, Netherlands Cancer Institute, 1066 CX - Amsterdam/NL
  • 2 Dept Of Medical Oncology, Netherlands Cancer Institute, 1066 CX - Amsterdam/NL
  • 3 Biostatistics Facility, Netherlands Cancer Institute, 1066 CX - Amsterdam/NL
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Abstract 119P

Background

Patients with triple-negative breast cancer (TNBC) that have a BRCA1-like phenotype - a specific pattern of DNA copy number aberrations similar to that of BRCA1-mutated tumours - benefit significantly from intensified platinum-based chemotherapy (IPB-chemo) compared to those without. To further molecularly characterise BRCA1-like TNBC tumours, we set out a multiomics analysis making use of published data sets.

Methods

We made use of 3 clinical data sets (TCGA, RATHER, MATADOR). Sparse generalised canonical correlation analysis and logistic regression were performed on the multiomics data sets to identify features most strongly correlated with BRCA1-like status. Next, to characterise the subgroups, differential gene expression, active-subnetwork-oriented pathway enrichment analyses and cell type deconvolution of the bulk tissue mRNA-seq data were performed.

Results

We identified n = 84/1097, 62/126 and 46/495 BRCA1-like TNBCs in the TCGA, RATHER and MATADOR cohorts respectively. Two subgroups of BRCA1-like TNBCs were discerned that are characterised by a more or less profound copy-number loss on chromosome 5q. Deconvolution analyses revealed that BRCA1-like tumours with less 5q loss (n=65/130) are associated with higher tumour-infiltrating lymphocyte levels (p=0.001) and higher immune cell type percentages (p=0.006). This BRCA1-like subgroup was characterised by a gene expression profile that strongly associates with a number of cell-mediated immunity related pathways, such as the PD-L1/PD-1 pathway (p<0.001) and natural killer cell mediated cytotoxicity (p<0.001).

Conclusions

By analysing multiomics data from n = 192 patients with BRCA1-like triple-negative breast cancer, we found indications for the presence of distinct subgroups of which one has immunomodulatory features. How these BRCA1-like, TNBC subgroups may direct immunotherapy strategies will be addressed in follow-up studies.

Clinical trial identification

The MATADOR study: ISRCTN61893718; The RATHER Consortium: https://ratherproject.com/; TCGA Program: https://www.cancer.gov/about-nci/organization/ccg/research/structural-genomics/tcga.

Editorial acknowledgement

Legal entity responsible for the study

Netherlands Cancer Institute.

Funding

For MATADOR: Dutch Cancer Society, Sanofi and Amgen; For RATHER: European Commission (7th Framework Programme of Research and Development).

Disclosure

S.C. Linn: Financial Interests, Institutional, Research Grant, unrestricted research grant to conduct the MATADOR study (ISRCTN61893718): Sanofi and Amgen; Financial Interests, Institutional, Funding, research support funding: Agendia, Amgen, AstraZeneca, Eurocept-pharmaceuticals, Novartis, Immunomedics, Genentech, Pfizer, Roche, Sanofi, Tesaro; Non-Financial Interests, Personal, Advisory Board: Cergentis, IBM, Novartis, Pfizer, Roche, Sanofi; Non-Financial Interests, Institutional, Other, non-financial support: AstraZeneca, Genentech, Novartis, Roche, Tesaro, Immunomedics; Financial Interests, Institutional, Other, educational financial support: Bayer, Daiichi Sankyo. All other authors have declared no conflicts of interest.

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