No abstract

PURPOSE Evidence-based guidelines recommend cascade genetic counseling and testing for hereditary cancer syndromes, providing relatives the opportunity for early detection and prevention of cancer. The current standard is for patients to contact and encourage relatives (patient-mediated contact) to undergo counseling and testing. Direct relative contact by the medical team or testing laboratory has shown promise but is complicated by privacy laws and lack of infrastructure. We sought to compare outcomes associated with patient-mediated and direct relative contact for hereditary cancer cascade genetic counseling and testing in the first meta-analysis on this topic. MATERIALS AND METHODS We conducted a systematic review and meta-analysis in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PROSPERO No.: CRD42020134276). We searched key electronic databases to identify studies evaluating hereditary cancer cascade testing. Eligible trials were subjected to meta-analysis. RESULTS Eighty-seven studies met inclusion criteria. Among relatives included in the meta-analysis, 48% (95% CI, 38 to 58) underwent cascade genetic counseling and 41% (95% CI, 34 to 48) cascade genetic testing. Compared with the patient-mediated approach, direct relative contact resulted in significantly higher uptake of genetic counseling for all relatives (63% [95% CI, 49 to 75] v 35% [95% CI, 24 to 48]) and genetic testing for first-degree relatives (62% [95% CI, 49 to 73] v 40% [95% CI, 32 to 48]). Methods of direct contact included telephone calls, letters, and e-mails; respective rates of genetic testing completion were 61% (95% CI, 51 to 70), 48% (95% CI, 37 to 59), and 48% (95% CI, 45 to 50). CONCLUSION Most relatives at risk for hereditary cancer do not undergo cascade genetic counseling and testing, forgoing potentially life-saving medical interventions. Compared with patient-mediated contact, direct relative contact increased rates of cascade genetic counseling and testing, arguing for a shift in the care delivery paradigm, to be confirmed by randomized controlled trials.

No abstract

Background: Cascade genetic testing for hereditary cancer syndromes offers affected relatives the opportunity to pursue cancer screening and risk-reducing surgery and thus reduces morbidity and mortality. The purpose of this study was to measure the long-term utilization of targeted cancer prevention and quality of life among at-risk relatives offered clinician-facilitated cascade genetic testing.Methods: In a pilot study, at-risk relatives of patients with a hereditary cancer syndrome were contacted directly by the clinical team and offered telephone genetic counseling and genetic testing via an at-home, mailed saliva kit. Two-year follow-up results evaluating the use of targeted cancer prevention strategies and the quality of life for enrolled relatives were reported. Quality-of-life was measured with validated surveys, and scores were compared to the time of initial contact by the Wilcoxon signed-rank test. Results:Ninety-five at-risk relatives were enrolled in the initial pilot study, and 72 (76%) participated in the 2-year follow-up; 57 of these (79%) had completed genetic testing. Twenty-five of those 57 relatives (44%) were found to harbor an inherited pathogenic variant. Guideline-based cancer surveillance was recommended to 18 relatives; 13 (72%) completed at least one recommended screening, and six (33%) completed all recommended screenings. Risk-reducing surgery was recommended to 10 relatives; four (40%) completed a total of eight procedures. Quality-of-life surveys demonstrated low levels of anxiety, depression, distress, and uncertainty. Conclusions:The 2-year follow-up of the original pilot study revealed that clinicianfacilitated cascade testing resulted in genetically targeted cancer screening and prevention with preserved quality of life. These results, to be confirmed by larger

No abstract