BackgroundThe cancer genomics field has embraced the advent of precision oncology, and vast volumes of data have been mined for biomarkers of drug actionability. While some cancers, such as lung cancer, have detailed panels of actionable genomic biomarkers, sequencing panels have been less useful in breast cancer given its large number of cancer driver genes mutated at a relatively low frequency. Furthermore, mutation signatures have potential to assist in identifying homologous recombination deficient tumours for targeting with PARP inhibitor therapy.Patients and MethodsTo investigate whether whole genome sequencing could benefit breast cancer patients we initiated the Q-IMPROvE (Queensland-IMplementation of PRecision Oncology in brEast cancer) prospective pilot study. We report the analysis of matched tumour and normal genomes of 28 high-risk breast cancer patients undergoing treatment in the neo-adjuvant setting.ResultsUsing whole genome sequencing, we detected actionable events that would otherwise not have been identified. A quarter of patients demonstrated a defect in homologous recombination DNA repair using the HRDetect and HRD scores. Germline variants of importance (BRCA1, CHEK2) were identified in two patients that did not meet clinical guidelines for germline genetic testing. Somatically,TP53andPIK3CAwere the most commonly mutated breast cancer driver genes.ConclusionsWe have demonstrated the benefit of whole genome sequencing of both the tumour and germline for breast cancer patients otherwise not meeting clinical criteria for genetic health referrals.