Patients' Medical and Psychosocial Experiences After Detection of a <i>CDH1</i> Variant With Multigene Panel Testing.

Abstract

Germline <i>CDH1</i> pathogenic variants (PV) are associated with hereditary diffuse gastric cancer and lobular breast cancer. Although prevalence of <i>CDH1</i> PV is low in the general population, detection of these variants is increasing with the growing use of multigene panel testing. Little is known about the experiences of individuals tested for <i>CDH1</i> variants in the multigene panel testing era. Participants recruited from the Prospective Registry of Multiplex Testing completed a cross-sectional self-report survey regarding <i>CDH1</i> genetic testing experiences, medical management, and psychosocial adaptation. Discordance existed in interpretations of <i>CDH1</i> results; 13.3% of cases had disagreements in variant classifications among commercial laboratories, and 21.4% had disagreements between participant self-report and ClinVar classification. Survey data were available from 57 individuals reporting either PV (n = 16) or variants of uncertain significance (VUS; n = 41). Those with PV were more likely than those with VUS to report receiving a recommendation for prophylactic gastrectomy, although only 40.0% of those with PV received this recommendation. Participants with VUS were less satisfied with their health care providers' knowledge and reported less <i>CDH1</i> knowledge, distress, and worry about discrimination. Participants with PV perceived greater breast cancer risks, but similar gastric cancer risks, as those with VUS. Few individuals with <i>CDH1</i> PV report receiving recommendations for prophylactic gastrectomy, and no differences in perceived gastric cancer risk were observed based on participants' <i>CDH1</i> results, suggesting serious unmet informational needs.