Real-World Concordance between Germline and Tumour BRCA1/2 Status in Epithelial Ovarian Cancer.

Simple Summary: Approximately 10–15% of patients with epithelial ovarian cancer have an inherited (germline) BRCA1 or BRCA2 mutation. Following a diagnosis of epithelial ovarian cancer, patients are routinely tested for germline and/or somatic (tumour) BRCA1/2 mutations. Our study shows that if germline BRCA1/2 testing is only performed for patients with a positive tumour BRCA1/2 test result, and tumour testing is performed using Myriad's myChoice^® companion diagnostic, a proportion of germline BRCA1/2 large rearrangements could be missed. If paired germline-tumour DNA testing is not possible for all patients, our data shows that it would be appropriate to test all patients with epithelial ovarian cancer aged < 79 years old for germline BRCA1/2 mutations, regardless of the tumour BRCA1/2 result, whilst only needing to test patients aged ≥ 80 years old for a germline BRCA1/2 mutation if they have a positive tumour BRCA1/2 result. Patients diagnosed with epithelial ovarian cancer may undergo reflex tumour BRCA1/2 testing followed by germline BRCA1/2 testing in patients with a positive tumour test result. This testing model relies on tumour BRCA1/2 tests being able to detect all types of pathogenic variant. We analysed germline and tumour BRCA1/2 test results from patients treated for epithelial ovarian cancer at our specialist oncological referral centre. Tumour BRCA1/2 testing was performed using the next-generation sequencing (NGS)-based myChoice^® companion diagnostic (CDx; Myriad Genetics, Inc.). Germline BRCA1/2 testing was performed in the North West Genomic Laboratory Hub using NGS and multiplex ligation-dependent probe amplification. Between 11 April 2021 and 11 October 2023, 382 patients were successfully tested for tumour BRCA1 and BRCA2 variants. Of these, 367 (96.1%) patients were tested for germline BRCA1/2 variants. In those patients who underwent tumour and germline testing, 15.3% (56/367) had a BRCA1/2 pathogenic variant (36 germline and 20 somatic). All germline BRCA1/2 pathogenic small sequencing variants were detected in tumour DNA. By contrast, 3 out of 8 germline BRCA1/2 pathogenic large rearrangements were not reported in tumour DNA. The overall concordance of germline BRCA1/2 pathogenic variants detected in germline and tumour DNA was clinically acceptable at 91.7% (33/36). The myChoice^® CDx was able to detect most germline BRCA1/2 pathogenic variants in tumour DNA, although a proportion of pathogenic large rearrangements were not reported. If Myriad's myChoice^® CDx is used for tumour BRCA1/2 testing, our data supports a testing strategy of germline and tumour BRCA1/2 testing in all patients diagnosed with epithelial ovarian cancer aged < 79 years old, with germline BRCA1/2 testing only necessary for patients aged ≥ 80 years old with a tumour BRCA1/2 pathogenic variant. [ABSTRACT FROM AUTHOR]