Facilitated cascade genetic testing with navigation support raised testing uptake among first-degree relatives (FDRs) of individuals with BRCA1/2 pathogenic variants from 50.7% to 73.2% at 6 months compared with standard care, according to results of a randomized controlled trial (NCT04613440) published in the Journal of Clinical Oncology. By 18 months, 90% of FDRs in the intervention arm had completed testing. Free germline testing was available to relatives in both arms.
“When we provided navigation to help people through the testing process, we noticed a meaningful difference in utilization and how soon people completed their testing,” lead author Roni Nitecki Wilke, MD, MPH, assistant professor in the Department of Gynecologic Oncology and Reproductive Medicine at The University of Texas MD Anderson Cancer Center, said in a news release.
Why does cascade genetic testing matter for BRCA1/2 families?
BRCA1/2 pathogenic variants follow autosomal dominant inheritance, giving each FDR a 50% chance of carrying the familial variant. Relatives identified through cascade testing become eligible for screening and risk-reducing interventions, but uptake under the current letter-based model is low.
“The way we do it in standard of care just doesn’t work and less than a third of patients actually get tested,” Wilke said in an interview with Oncology Nursing News.
A prior single-institution study of clinician-facilitated cascade testing reported 58% uptake among relatives but had no standard-of-care comparator.
How was the trial designed?
Investigators cluster-randomized 151 probands with newly diagnosed BRCA1 (52%) or BRCA2 (48%) germline pathogenic variants; 72% had a prior cancer diagnosis. Randomization was stratified by personal cancer history, number of FDRs (1-2 vs ≥3), and time since genetic testing (≤6 months vs >6-12 months).
Untested adult FDRs were enrolled: 142 in the intervention arm and 144 in the control arm.
Intervention arm: navigation support plus access to genetic testing servicesControl arm: a family letter, consistent with standard clinical practiceBoth arms: free germline genetic testing on requestPrimary end point: completion of genetic testing at 6 monthsWhat did the trial find?
At 6 months, 73.2% (adjusted 95% CI, 64.4%-82.1%) of FDRs in the intervention arm completed testing vs 50.7% (adjusted 95% CI, 41.0%-60.4%) in the control arm (P < .001).