Clinical implications of germline and somatic genetic testing in ovarian carcinoma: BRCA and beyond. The PERSONA-Ovary trial.

BRCA1, BRCA2

Pathogenic or likely pathogenic germline variants in ovarian cancer susceptibility genes, including BRCA1 and BRCA2

The prospective PERSONA-Ovary study offered unselected germline multigene panel testing to 320 consecutive patients with ovarian carcinoma at a tertiary cancer centre (2018-2021). A pathogenic or likely pathogenic variant was found in 95 patients (29.7%), 81 in ovarian cancer susceptibility genes and 60 in BRCA1 (n=43) or BRCA2 (n=17). Germline testing was informative in all patients, but median turnaround time reached 221 days (IQR 173-284), improving significantly across study periods. Germline-somatic BRCA1/BRCA2 concordance was 94.0% (κ=0.82); a germline-first strategy with reflex tumour testing detected all carriers with fewer assays than parallel testing, whereas the tumour-first strategy, the most economical (366 vs 596 assays), missed two germline carriers (detection rate 96.3%).

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Nearly three in ten patients carry a germline variant: constitutional testing should be systematic in ovarian carcinoma, with direct consequences for PARP inhibitor access and cascade testing of relatives. The practical message concerns strategy: starting from tumour testing alone misses germline carriers, while a median turnaround of 221 days remains incompatible with treatment decisions. Single-centre study, whose turnaround times reflect local organisation.

Analysis by Dr Thibaut Benquey