Breast cancer comprises of a group of diseases many of the most aggressive forms of which are characterised by high levels of chromosome instability that are driven by abnormalities in the DNA damage response. This has opened up the possibility of targeting these abnormalities and exposing tumour specific vulnerabilities. Abnormalities in homologous recombination DNA repair, driven by loss of function of BRCA1 and BRCA2, and the synthetic lethal targeting of these vulnerabilities with PARP inhibitors have been a “poster child” for these approaches.

In my lecture I will address some of the wider analyses of homologous recombination deficiency in breast cancer and some novel drivers of abnormalities in the DNA damage response and maintenance of genome instability in TNBC. I will also discuss a novel mechanism by which HR deficient TNBCs may cope with the replication stress induced by HR deficiency revealed by my laboratory.