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

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.