The Queensland IMplementation of PRecision Oncology in brEast cancer (Q-IMPROvE) pilot study

Background The 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 Methods To 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. Results Using 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, TP53 and PIK3CA were the most commonly mutated breast cancer driver genes. Conclusions We 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. ### Competing Interest Statement OK has consulted for XING Technologies. JVP and NWa are founders and shareholders of genomiQa Pty Ltd, and members of its board. GH is the clinical genomics lead at genomiQa Pty Ltd. ### Clinical Trial ACTRN12621001285842 ### Funding Statement This study was funded by Queensland Health, through Queensland Genomics. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics committees of Royal Brisbane and Women's Hospital and The University of Queensland gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors