Cascade testing in an ovarian cancer traceback genetic testing program

Abstract

Approximately 20% of individuals diagnosed with ovarian cancer (OC) have an inherited pathogenic or likely pathogenic variant (P/LP) in a cancer risk gene. Though genetic testing for hereditary cancer risk is currently recommended at OC diagnosis, individuals who have not received risk information and their at-risk relatives (ARR) can benefit from genetic testing at any point. In a single-arm implementation study, the Genetic Risk Assessment in Ovarian CancEr (GRACE) study offered traceback genetic testing using a panel of cancer risk genes to (1) living survivors with a prior OC diagnosis who had not received genetic testing at diagnosis and (2) first-degree relatives of deceased eligible probands with a prior OC diagnosis who had not received genetic testing. For survivors and first-degree relatives with a positive result (i.e., P/LP detected), we offered cascade testing to ARR, including providing support resources to facilitate communication with their relatives and offering to directly contact relatives. Traceback testing occurred on average 10-12 years from the incident OC diagnosis, resulting in 20 positive findings with 93 ARR eligible for cascade testing. Overall, cascade testing uptake was 38%, with similar rates among relatives of living (40%) and deceased (33%) probands. Cascade testing identified 11 individuals with OC-risk variants and 3 incidental findings in genes not associated with OC risk. Women were more likely to complete cascade testing than men (45% vs. 30%, respectively). Initially, only two probands consented to direct contact with ARR by the study genetic counselor; 6 additional probands requested direct contact with relatives over subsequent interactions. These findings represent some of the first U.S. data available on cascade testing outcomes of traceback programs and suggest feasibility and effectiveness in U.S. health system settings.