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Poster session 01

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


10 Sep 2022


Poster session 01


Cytotoxic Therapy

Tumour Site

Breast Cancer


Terry Wing Sheung Chan


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


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

Abstract 119P


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.


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.


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).


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.


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


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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