Pilot program within NHS of R208 seven-gene germline genetic testing in unselected cases of breast cancer delivered using clinician-light pathway: Interim service evaluation findings from first 1756 patients

Abstract

Background: The BRCA-DIRECT clinician-light pathway for germline genetic testing involves; (i) streamlined provision of information about genetic testing to patients; (ii) a patient-directed pathway for DNA collection and consent, by use of at-home saliva sampling; and (iii) a support via dedicated administrative and genetics telephone helplines. We have now piloted the pathway for standard-of-care NHS mainstreaming within 15 varied breast oncology and surgical units, with testing eligibility expanded to all new presentations of breast cancer. Method(s): Service evaluation approval was attained. Preliminary data was collected and analysed, evaluating: outcomes from unselected genetic testing, resource requirements for delivering the pathway, and impact of implementing BRCA-DIRECT on breast and genetics clinical teams. Result(s): At interim analysis, 1,756 patients referred for genetic testing via BRCA-DIRECT had completed their involvement. The pickup rate of germline pathogenic variants (gPVs) in those consenting to testing was 5.1% overall; 3.9% in BRCA1/2 or PALB2 and 1.3% in ATM, CHEK2 and RAD51C/D. National test directory 'R208' criteria would have identified 51.5% and 4.5% of gPVs in respective genes. Breast oncology/surgical professionals expressed strong preference for BRCA-DIRECT to continue (18/18, 100%). Clinical genetics professionals reported decreasing referrals (10/15, 66.7%), with 13/17 (76.5%) expressing they would support continuation. Conclusion(s): Interim results indicate feasibility and acceptability of implementing the BRCA-DIRECT pathway for mainstream testing. Highlighting opportunity and value in updating eligibility criteria. Alterations will require balancing: simplification of eligibility assessment for mainstreaming and increased pickup of gPVs in highly clinically actionable genes (versus lower penetrance gPVs). Copyright © 2025