Facilitated Cascade Genetic Testing for Relatives of Individuals With BRCA1/2 Pathogenic Variants: A Randomized Controlled Trial.

Authors

Roni Nitecki Wilke, Haley A Moss, Maria D Iniesta, Xun Xu, Sarah Linhart, Ravi N Sharaf, Alexander Melamed, Karen H Lu, J Alejandro Rauh-Hain, Melissa K Frey

Published in

Journal of clinical oncology : official journal of the American Society of Clinical Oncology. Pages JCO2600735. Sep 29, 2026. Epub Sep 29, 2026.

Abstract

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.
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.
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.
In this randomized trial, facilitated CGT significantly increased genetic testing uptake among FDRs of probands with BRCA1/2 pathogenic variants compared with standard care.

PMID:
42809807
Bibliographic data and abstract were imported from PubMed on 30 Sep 2026.

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