Facilitated Cascade Genetic Testing for Relatives of Individuals With BRCA1/2 Pathogenic Variants: A Randomized Controlled Trial
In brief
Navigation raises BRCA-relative testing from 51% to 73% in six months
In this randomized trial, 73% of adult first-degree relatives offered navigation and testing support completed genetic testing by six months, compared with 51% receiving standard care; testing was free in both groups. By 18 months, 90% of relatives in the supported group had tested, and 46% of those tested carried a pathogenic or likely pathogenic variant, underscoring the potential to identify relatives at inherited cancer risk.
- Journal
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology (Q1)
- Published
- 29 September 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Roni Nitecki Wilke, Haley A Moss, Maria D Iniesta, Xun Xu, Sarah Linhart, Ravi N Sharaf, et al.
- PMID
- 42809807
- DOI
- 10.1200/JCO-26-00735
Why clinicians should know about it
- Picked for Breast and Endocrine Surgery (top studies of the week, 25 October 2026): Phase III RCT, practice-changing for adjuvant therapy
Abstract
PURPOSE: Despite the potential for substantial public health impact of cascade genetic testing (CGT), few at-risk relatives complete testing. We compared facilitated CGT with standard of care. METHODS: Probands with newly diagnosed BRCA1/2 germline pathogenic variants were cluster-randomized to a facilitated cascade testing intervention or standard care. Random assignment occurred at the proband level and was stratified by personal cancer history, the number of first-degree relatives (FDRs; 1-2 v ≥3), and time since genetic testing (≤6 months v >6-12 months). Adult FDRs without prior testing per self-report were enrolled. The intervention included navigation support and access to genetic testing services; control FDRs received a letter, consistent with standard clinical practice. Free germline genetic testing was available to all FDRs regardless of arm assignment. The primary outcome was completion of genetic testing at 6 months, compared using a two-sided Cochran-Mantel-Haenszel test. RESULTS: Among 151 probands with BRCA1 (52%) or BRCA2 (48%) pathogenic variants, 72% had a prior cancer diagnosis. Probands were randomly assigned, with 142 and 144 FDRs assigned to the intervention and control arms, respectively. At 6 months, genetic testing uptake was significantly higher among FDRs in the intervention group compared with the control group (73.2% [adjusted 95% CI, 64.4 to 82.1] v 50.7% [adjusted 95% CI, 41.0 to 60.4]; P < .001). By 18 months, 90% of intervention FDRs completed genetic testing. Among 206 FDRs who completed testing, 95 (46%) were found to have a pathogenic or likely pathogenic variant; of these, 82 (86%) carried the familial variant. CONCLUSION: In this randomized trial, facilitated CGT significantly increased genetic testing uptake among FDRs of probands with BRCA1/2 pathogenic variants compared with standard care.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.