Routine germline genetic testing in 3552 unselected NHS breast cancer patients: evidence informing testing criteria and implementation of a 'BRCA-DIRECT' mainstreaming pathway.

Germline testing of breast cancer susceptibility genes (BRCA1, BRCA2, PALB2, CHEK2, ATM, RAD51C, RAD51D)

The NT-MBGT programme tested 3515 unselected, newly diagnosed breast cancer patients across 14 NHS units through a clinician-light 'BRCA-DIRECT' mainstreaming pathway (home saliva testing, postal consent, access to a genetic counsellor telephone helpline). The germline pathogenic variant pick-up rate was 4.7% (166 variants across seven susceptibility genes). Applying current NHS eligibility criteria would have offered testing to only 20.6% of patients, identifying 49.2% of variants in high-penetrance genes (BRCA1/BRCA2/PALB2) and 18.2% in intermediate-penetrance genes (CHEK2/ATM/RAD51C/RAD51D). 'Ultra-simple' criteria could raise sensitivity to 81.1% and 70.4% respectively while expanding testing to 49.7% of cases. The pathway was acceptable and feasible, with high satisfaction and no added workforce burden.

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

This study provides robust evidence for expanding germline testing through mainstreaming without further burdening genetics services, a key organisational challenge. Current eligibility criteria miss half of carriers, arguing for broad testing or simplified criteria. The clinician-light model is directly transferable to other health systems facing shortages in genetic counselling.

Analysis by Dr Thibaut Benquey