LAUSR

Abstract Background Randomised phase 3 trials have demonstrated that poly (ADP-ribose) polymerase (PARP) inhibitors significantly improve progression-free survival in BRCA-mutant high-grade serous and endometrioid ovarian carcinoma. Consequently, the demand for germline and tumour BRCA1/2testing has increased significantly throughout the UK. We report results from a tumour BRCA1/2testing service available to cancer centres across England, Wales and Northern Ireland from July 2017 to February 2019. Methods DNA extracted from formalin fixed, paraffin-embedded tumour samples underwent next generation sequencing for BRCA1/2 variants. Eligibility criteria included relapsed, platinum-sensitive ovarian, fallopian tube or primary peritoneal cancer with germline BRCA1/2wild-type or unknown germline. Patients also had to have received ≥2 prior lines of platinum-based chemotherapy. A confirmatory histopathology report was requested as part of the tumour BRCA1/2testing service. Results Two hundred and ninety-three histologically-confirmed high-grade serous and/or endometrioid ovarian cancer tumour samples underwent tumour BRCA1/2testing. The prevalence of pathogenic (class 5) or likely pathogenic (class 4) variants was 17.7% (52/293). The germline BRCA1/2was wild-type for 185/293 (63.1%) of patients, with the remaining 36.9% (108/293) with germline BRCA1/2unknown. There were at least 36 (12.3%) pathogenic/likely pathogenic somatic BRCA1/2variants detected. The allele fraction for somatic BRCA1/2pathogenic variants ranged from 0.06 to 0.98, with 50% (18/36) reported with an allele fraction of ≥ 0.5 (50%), in keeping with putative biallelic loss-of-function. Conclusions Prospective evaluation of paired germline and tumour BRCA1/2testing in all women who are diagnosed with platinum-sensitive high-grade serous and/or endometrioid ovarian cancer in the UK is now required to validate these findings. Legal entity responsible for the study AstraZeneca. Funding AstraZeneca. Disclosure All authors have declared no conflicts of interest.