Prevalence of BRCA1/2 variants in an Ovarian Cancer Cohort: outcomes from a Nationwide Testing Program

BRCA1

Germline and somatic pathogenic variants in BRCA1 and BRCA2, including recurrent variants in regional clusters (BRCA1 c.5266dup, BRCA1 c.1175_1214del, BRCA2 c.4398_4402del).

Ireland implemented a nationwide, oncology-led BRCA1/BRCA2 testing pathway for patients with ovarian cancer in 2020. Among 535 patients enrolled between January 2020 and December 2023 (median age 65.5 years), 455 (85.0%) underwent germline blood testing and 360 (67.2%) tumour testing, with 292 (54.6%) tested in paired fashion. A germline clinically actionable variant was identified in 10.3% of those tested (47/455) and a variant of uncertain significance in 2.1% (10/455); among the 262 paired patients with negative germline results, 9.5% (25/262) carried a somatic actionable BRCA variant. Recurrent germline variants were found in regional clusters, including BRCA1 c.5266dup, BRCA1 c.1175_1214del and BRCA2 c.4398_4402del.

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

10.3% actionable germline variants is lower than the 13-18% often quoted, and the authors say so: the value of work like this is precisely to provide the real figure for an entire country rather than an expert centre, recalibrating expectations in clinic. The operational result lies elsewhere: 9.5% somatic variants among paired germline-negative patients, close to one patient in ten who would have no access to a PARP inhibitor without tumour testing. The 54.6% paired testing rate is the pathway's real weak point and deserves to be tracked as an indicator.

Analysis by Dr Thibaut Benquey