We have received funding to harness ‘omics technology and national expertise to bring precision medicine to breast cancer care. This will be achieved by implementing Whole Genome Sequencing in patients with high-grade breast cancer undergoing neoadjuvant therapy in order to improve second-line therapeutic decision-making and outcomes. This proposal will evaluate the implementation of precision oncology in high-risk breast cancer patients by sequencing whole genomes and assessing potential clinical intervention outcomes, as well as their cost-benefit to the health system. The ability of whole genome sequencing to identify changes predictive of specific therapeutic strategies, dose-modification of existing therapies (pharmacogenomics), as well as triage to clinical trials will be examined. We will generate data to explore MR-Imaging and its relationship with prognosis and tumour genotype. We will innovate in the liquid biopsy space by investigating methylation status of circulating tumour DNA and evaluating circulating tumour cell transcriptomes in pre- and post-chemotherapy blood samples, with a view to the development of predictive and prognostic biomarkers.