A pilot study to increase cascade genetic risk education and testing in families with hereditary cancer syndromes.

Abstract

378 Background: There is great need to build and evaluate tools and strategies to improve cascade genetic risk evaluation in families at high risk for hereditary cancer. The Genetic Information and Family Testing (GIFT) Trial is a population-based intervention that will examine features of a virtual platform that provides genetic risk education (GRE) and low-cost genetic testing (GT) to relatives of 5000 adult patients diagnosed with cancer in 2018-19 in Georgia and California and who tested positive for a clinically actionable germline pathogenic variant (PV). We present findings of a pilot study that informed the GIFT Trial protocol and platform features. Methods: We surveyed 277 women diagnosed with breast cancer in 2017, reported to the Georgia SEER registry, and who tested positive for a clinically actionable PV in a cancer-associated gene. We then invited respondent patients to enroll in the intervention phase which provided online GRE, human pretest genetic navigator support, and an offer of low-cost GT through Color Health, Inc. to all untested 1st or 2nd degree relatives. Respondent patients were eligible for the intervention if they reported a PV on genetic testing and had at least one relative who had not received GT. Enrolled patients invited relatives through the platform by providing email addresses. Family clusters were block randomized to free vs $50 test costs at the time of the initial patient invitation. Results: 125 of 277 patients (45.2%) returned surveys: median age was 51 and 22% were African American. The most common PV reported by patients were BRCA2 (25.7%), BRCA1 (19.5%), CHEK2 (20.4%), ATM (8.8%) and PALB2 (7.1%). Disclosure of genetic test results to relatives was quite high: 83.6% of patients reported that they discussed results with all their daughters vs 69.4% with sons; 78.1% discussed their results with all sisters vs 61.8% with all brothers. The median number of patient-reported untested relatives in a family was 9 (25th-75th percentile: 4-14). Most respondents were eligible for the trial offer (113 of 125, 90.4%). Overall, results were similar between the free test arm and $50 test arm: In the free testing arm, 20 patient participants invited 28 relatives; 12 relatives enrolled, and all 12 relatives ordered testing. In the $50 arm, 16 patient participants invited 38 relatives of whom 18 enrolled and all 18 ordered testing. For the 66 relatives invited by the patient participants: 47 (71.2%) were first degree (8 parents, 22 siblings, and 17 children) and about half of the relatives were men (47.0%). Conclusions: Breast cancer patients with PVs make substantial efforts to communicate with family members about genetic risk but most relatives do not receive GT. Our study findings suggest that a low-cost online navigator-supported intervention can directly engage relatives to increase cascade genetic risk education and testing with little difference in uptake by test cost arms.