Clinician-facilitated cascade genetic testing among first-, second-, and third-degree relatives.

Abstract

e13584 Background: Cascade genetic testing enables identification of individuals at increased hereditary cancer risk, yet most efforts largely focus on first-degree relatives, leaving many pathogenic variant carriers unidentified. We examined uptake of clinician-facilitated cascade testing when extended to second- and third-degree relatives. Methods: In a prospective IRB-approved clinical trial at a single academic gynecologic oncology clinic, probands with BRCA1/2 pathogenic variants were offered clinician-facilitated cascade testing. Probands provided contact information for relatives, who were then contacted by the study team via telephone. Interested relatives completed genetic counseling and were mailed no-cost saliva-based multigene panel genetic testing kits. The primary outcome was genetic testing uptake at 6 months among first-degree versus extended (second- and third-degree) relatives. Results: Between 9/2022–9/2024, 37 probands enrolled and identified 61 at-risk relatives. Fifty-one (83.6%) relatives were successfully contacted. Among relatives successfully reached, 39 (76.5%) were interested in clinician-facilitated cascade testing. Extended relatives were significantly more likely to be interested in clinician-facilitated cascade testing compared to first-degree relatives (95.0% [19/20] vs. 64.5% [20/31]; p = .02). Reasons for declining clinician-facilitated testing included prior testing (n = 2) and lack of interest (n = 9) among first-degree relatives, and lack of interest among one extended relative. At 6-month follow-up, 27/39 (69.2%) relatives completed testing, with similar completion rates across groups (first-degree: 70.0% [14/20]; extended: 57.9% [11/19]; p = 0.51). Pathogenic variants were detected in 10/27 (37.0%) relatives, including 6/14 (42.9%) first-degree and 4/11 (36.4%) extended relatives ( p = 1.00). For interested relatives, the median age was 51 (IQR 32-65), and 38.5% were female. Conclusions: Extended relatives showed high receptivity to clinician-facilitated cascade genetic testing, with comparable testing completion and pathogenic variant detection to first-degree relatives. Expanding cascade testing beyond immediate family members may represent an underutilized strategy to improve identification of individuals at hereditary cancer risk. Clinical trial information: NCT04613440 . Outcomes of clinician-facilitated cascade genetic testing for first-degree relatives and extended (second- and third-degree) relatives. Step First-degree relatives Extended Relatives Total p-value Relatives successfully contacted 31 20 51 - Interested in clinician-facilitated cascade testing 20 (64.5%) 19 (95.0%) 39 (76.5%) 0.02 Completed cascade genetic testing 14 (70.0%) 11 (57.9%) 27 (69.2%) 0.51 Pathogenic variants detected 6 (42.9%) 4 (36.4%) 10 (37.0%) 1.00 Percentages are calculated relative to the number in the row above. p-values from Fisher’s exact test.