A pilot study to increase cascade genetic testing in families with hereditary cancer syndromes.
Authors: Katz Steven J. , Tocco Rachel , Hawley Sarah T. , An Lawrence , Hodan Rachel , Ward Kevin C , Kurian Allison W. 
Published: June 2022

10602 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 (CA254822) is a population-based intervention that examines features of a virtual platform that provides genetic risk education (GRE) and low-cost genetic testing (GT) to relatives of adult patients diagnosed with cancer in 2018-19 in Georgia and California and tested positive for a clinically relevant germline pathogenic variant (PV). We present findings of a pilot study intended to inform 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 received genetic testing (95% of whom had a clinically relevant PV). 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: At study midpoint, 117 of 277 patients (42%) had returned surveys: median age was 51 and 22% were African American. The most frequent PVs reported by the patients were BRCA1/2 (41%), CHEK2 (21%), and PALB2 (8%). Half (54%) had previously encouraged all of their brothers to get GT and 71% had encouraged all of their sisters to get GT. Three-quarters (78%) strongly agreed it was important for relatives to understand their genetic risk for cancer, and half (54%) strongly agreed they would like to make it easier for relatives to get genetic testing. The median number of patient-reported untested relatives in a family was 8.5 (25th-75th percentile: 4-14). Most respondent patients were eligible for the intervention phase (N = 108, 93%). About one-quarter had enrolled in the intervention at midpoint (16 of 53 in no-cost arm vs 16 of 55 in $50 arm). Patients in the no-cost arm invited 21 relatives, 10 of whom had enrolled with 8 ordering GT (38% of invited relatives). Patients in the $50 arm invited 38 relatives, 18 of whom had enrolled with 17 ordering GT (45% of invited relatives). Overall, about half of enrolled relatives (46%) were men. Conclusions: Breast cancer patients with PVs make substantial efforts to communicate with family members about genetic risk; but they strongly endorse the need for additional support to facilitate this complex communication. Interim pilot findings suggest that a low-cost online navigator-supported intervention can directly engage relatives with little difference in GT uptake by test cost arms.