Abstract MS2-3: MS2-3 Clinical implications of DNA repair and genome instability research

Abstract

Abstract Breast cancer has now been subjected to extensive molecular characterisation. Although much attention has focused on transcriptional profiling, with consequent identification of a number of biological sub-types, it is clear that breast cancers show significant variability in their somatic genome. Breast cancers are diseases that are largely dominated by copy number aberrations (CNAs) rather than single nucleotide variants (SNVs). Although HER2 is the poster child CNA driven therapeutic target a number of other mutation and CNA candidates are being pursued. The mutational processes that drive the different forms of genomic instability in breast cancer are increasingly understood and have been described in the last year. These mutational and rearrangement signatures may reveal aberrations in the DNA damage response that themselves represent a vulnerability and a therapeutic target. I will discuss a range of strategies and clinical trials being employed to target DNA repair, genome instability and consequent replicative stress in breast cancer. I will also discuss the state of development of assays that categorise a range of forms of mutational signature and genome instability which may act in future as predictive biomarkers of therapy response or resistance to DNA damage response targeting therapies with utility in the clinic. Citation Format: Tutt A. MS2-3 Clinical implications of DNA repair and genome instability research [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr MS2-3.