From genetic testing to prevention: an integrated clinical pathway for hereditary risk assessment in tubo-ovarian cancer

BRCA1

Germline pathogenic variants in BRCA1 and BRCA2, in mismatch repair genes, and in BRIP1, RAD51C, RAD51D and PALB2, each with its own penetrance and age-specific risk.

This narrative review sets out a continuous clinical pathway from germline testing to prevention, for patients with epithelial tubo-ovarian cancer and for their relatives. The authors note that family-history-based referral alone misses a substantial share of carriers, justifying testing offered to all patients. BRCA1 and BRCA2 remain the highest-impact genes, but Lynch syndrome genes, BRIP1, RAD51C, RAD51D and PALB2 each require distinct counselling, with gene-specific penetrance, age-specific risk, comorbidities, reproductive plans and menopausal consequences shaping the timing of risk-reducing surgery. Tumour testing improves therapeutic selection and may reveal a possibly hereditary variant, but does not replace germline testing when hereditary evaluation is indicated.

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

The contribution of this synthesis is to move the measurement point: what should be counted and resourced is no longer the proportion of patients tested but the proportion of relatives actually tested through cascade referral, as an indicator of the care pathway. Framing cascade testing as a prevention intervention to be resourced, rather than a responsibility left to families, is the only angle that explains why uptake remains low despite index testing becoming routine. The reminder that tumour-only testing does not replace germline testing remains useful: it is a frequent confusion in tumour boards.

Analysis by Dr Thibaut Benquey