DOI: 10.1200/jco-26-00735 ISSN: 0732-183X
Facilitated Cascade Genetic Testing for Relatives of Individuals With
BRCA1/2
Pathogenic Variants: A Randomized Controlled Trial
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
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
BRCA
1/2
pathogenic variants compared with standard care.