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

BRCA1/2

Familial cascade testing after identification of a germline pathogenic BRCA1 or BRCA2 variant in the proband, with a navigation and test-access intervention

Few at-risk relatives complete cascade genetic testing despite its potential public health impact. This cluster-randomized trial enrolled 151 probands carrying a germline pathogenic BRCA1 (52%) or BRCA2 (48%) variant, with 142 first-degree relatives in the intervention arm (navigation support and access to testing) and 144 in the control arm (a letter), free testing being available in both arms. At 6 months, testing uptake was 73.2% in the intervention arm versus 50.7% in the control arm (P < .001), and 90% at 18 months in the intervention arm. Among the 206 relatives tested, 95 (46%) carried a pathogenic or likely pathogenic variant, of which 82 (86%) carried the familial variant.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

The 22.5-point gap at 6 months is clear and obtained by randomization, but the outcome measures test completion, not the cancer prevention that follows. Testing being free in both arms, the effect lies in the support itself; the control arm (a letter) corresponds, according to the authors, to usual clinical practice, which remains to be confirmed outside a research setting. The yield observed (46% pathogenic or likely pathogenic variants among relatives tested, 86% of them the familial variant) is a reminder that each relative tested is an opportunity for targeted prevention.

Analysis by Dr Thibaut Benquey