According to findings from a randomized controlled trial reported by Wilke et al in the Journal of Clinical Oncology, a clinician-facilitated approach to cascade genetic testing significantly increased genetic testing uptake among first-degree relatives of individuals with BRCA1 or BRCA2 pathogenic variants compared with standard care. The study evaluated whether proactive outreach and navigation support could improve genetic testing completion among first-degree relatives at increased risk of hereditary cancer.
Cascade genetic testing is a systematic method used to identify hidden hereditary or genetic conditions within a family by testing close blood relatives of a newly diagnosed individual, or proband.
Study Details
The unblinded, cluster-randomized FaCT trial enrolled individuals with a BRCA1 or BRCA2 pathogenic variant identified within the preceding 12 months at three U.S. academic medical centers. Of 173 individuals randomly assigned, 151 had at least one eligible first-degree relative enrolled and were considered evaluable. Among these individuals, 52% carried a BRCA1 pathogenic variant, 48% carried a BRCA2 pathogenic variant, and 72% had a prior cancer diagnosis.
A total of 286 first-degree relatives were enrolled, including 142 assigned to the facilitated cascade testing intervention and 144 assigned to standard care. Eligible relatives were adults who were aware of the familial pathogenic variant and had not previously undergone genetic testing.
In the intervention group, trained navigators directly contacted relatives and provided assistance with accessing genetic testing, ordering and returning saliva collection kits, and completing the testing process. In the control group, individuals with pathogenic variants received a family letter to share with relatives, consistent with standard clinical practice.
Free germline genetic testing was available to participants in both groups.
The primary endpoint was genetic testing completion at 6 months, with additional assessments through 18 months.
Key Results
At 6 months, genetic testing completion was significantly higher in the facilitated cascade testing group vs the standard-care group (73.2% vs 50.7%; adjusted 95% confidence interval [CI] = 64.4%–82.1% vs 41.0%–60.4%; P < .001).
Time-to-event analysis demonstrated that relatives receiving the facilitated intervention underwent genetic testing at nearly twice the rate of those receiving standard care (hazard ratio [HR] = 1.96, 95% CI = 1.46–2.63; P < .001). Median time to testing was 2.2 months in the intervention group compared with 3.8 months in the control group.
By 18 months, the estimated cumulative probability of genetic testing completion was 90% in the intervention group vs 62% in the control group. Testing uptake in both groups plateaued at approximately 9 months, after which few additional participants completed testing.
Among the 206 relatives who underwent genetic testing, 95 (46%) were found to carry a pathogenic or likely pathogenic variant, including 82 (86%) who carried the familial variant. Among the 41 women with newly identified BRCA1/2 pathogenic variants, 27% underwent breast magnetic resonance imaging, five underwent risk-reducing salpingo-oophorectomy, and four underwent mastectomy.
The investigators concluded: “In this randomized trial, facilitated [cascade genetic testing] significantly increased genetic testing uptake among [first-degree relatives] of probands with BRCA1/2 pathogenic variants compared with standard care.”
Roni Nitecki Wilke, MD, MPH, of the Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, is the corresponding author for the Journal of Clinical Oncology article.
DISCLOSURE: The study was supported by The Gray Foundation, the Kaleidoscope of Hope Ovarian Cancer Foundation, and others. For full disclosures of the study authors, visit ascopubs.org.
