Assessing the Efficacy of NCCN Genetic Testing Criteria in a Clinic-Based Population Screening Cohort

Abstract

Genetic testing criteria for hereditary cancer syndromes are used by clinics and insurance companies to determine coverage and testing options for at-risk individuals. Although these guidelines are considered best practices within the field, previous studies suggest that some individuals with hereditary cancer syndromes are not detected using these criteria. In this study, detailed chart review was performed for Mayo Clinic patients who were identified to have a pathogenic (PV) or likely pathogenic (LPV) variant through the TAPESTRY study. The Mayo Clinic’s TAPESTRY study is a population screen performed in collaboration with Helix to whole exome sequence 100,000 patients and provide genetic test results. Individuals are recruited to this study based on their status as a Mayo Clinic patient. Participants received results from ACMG Tier 1 conditions including Hereditary Breast and Ovarian Cancer syndrome (HBOC), Lynch syndrome (LS), and Familial Hypercholesterolemia. Five-hundred and fifty individuals with a PV or LPV in BRCA1, BRCA2, MLH1, MSH2, PMS2, MSH6, and/or EPCAM were identified through the TAPESTRY study. Detailed chart review was performed to collect demographic information, personal and family history, and satisfaction of NCCN criteria. Out of the 550 patients identified to have a PV/LPV, 33.8% did not meet NCCN criteria for genetic testing and 39.2% of all participants did not meet NCCN criteria for their hereditary cancer syndrome. 29.8% of participants identified to have a mutation in an HBOC gene did not meet any panel criteria, while 43.2% of participants with a LS gene did not meet any panel criteria. Individuals who did not have prior knowledge of their hereditary condition comprised 52.1% of the total participants; 51.9% of these patients did not meet any NCCN criteria for genetic testing. 60% of individuals who did not have prior knowledge of their mutation, did not meet NCCN criteria for their hereditary cancer condition. 47.4% of individuals who did notknow they had a PV/LPV in an HBOC gene did not meet any panel criteria, while 61.1% of individuals who did not know they had a PV/LPV in a LS gene did not meet any panel criteria. These results emphasize the need for expanded genetic testing criteria to better identify individuals at-risk for hereditary cancer syndromes. Modifications of current guidelines has the potential to increase genetic testing and result in more appropriate screening and management for high-risk individuals.