Homologous recombination DNA repair deficiency and PARP inhibition activity in primary triple negative breast cancer
Triple negative breast cancer (TNBC) encompasses molecularly different subgroups, with a subgroup harboring evidence of defective homologous recombination (HR) DNA repair. Within a phase 2 window clinical trial, RIO trial (EudraCT 2014-003319-12), we investigate the activity of PARP inhibitors in 43 patients with untreated TNBC. The primary endpoint, decreased Ki67, occurs in 12% of TNBC. Multiple different approaches identify HR deficiency in the majority of TNBC, 69% with the mutational-signature-based HRDetect assay. Cancers with mutational signatures of HR deficiency have a functional defect in HR. Following rucaparib treatment there is no association of Ki67 change with HR deficiency. In contrast, early circulating tumor DNA dynamics identify activity of rucaparib in cancers with mutation-signatures of HR deficiency, with rucaparib inducing expression of interferon response genes in HR deficient cancers. The majority of TNBCs have a defect in DNA repair, identifiable by mutational signature analysis, that may be targetable with PARP inhibitors.
- Type: Other
- Archiver: EGA European Genome-Phenome Archive
Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data
|EGAD00001006120||Illumina HiSeq 2500||39|
Homologous recombination DNA repair deficiency and PARP inhibition activity in primary triple negative breast cancer.
Nat Commun 11: 2020 2662