Psychosocial outcomes following germline multigene panel testing in an ethnically and economically diverse cohort of patients

Abstract

BACKGROUND:Little is known about the psychological outcomes of germline multigene panel testing, particularly among diverse patients and those with moderate-risk pathogenic variants (PVs). METHODS: Study participants (N = 1264) were counseled and tested with a 25-or 28-gene panel and completed a 3-month postresult survey including the Multidimensional Impact of Cancer Risk Assessment (MICRA). RESULTS: The mean age was 52 years, 80% were female, and 70% had cancer; 45% were non-Hispanic White, 37% were Hispanic, 10% were Asian, 3% were Black, and 5% had another race/ethnicity. Approximately 28% had a high school education or less, and 23% were non-English-speaking. The genetic test results were as follows: 7% had a high-risk PV, 6% had a moderate-risk PV, 35% had a variant of uncertain significance (VUS), and 52% were negative. Most participants (92%) had a total MICRA score ≤ 38, which corresponded to a mean response of "never," "rarely," or only "sometimes" reacting negatively to results. A multivariate analysis found that mean total MICRA scores were significantly higher (more uncertainty/distress) among high-and moderate-risk PV carriers (29.7 and 24.8, respectively) than those with a VUS or negative results (17.4 and 16.1, respectively). Having cancer or less education was associated with a significantly higher total MICRA score; race/ethnicity was not associated with the total MICRA score. High-and moderate-risk PV carriers did not differ significantly from one another in the total MICRA score, uncertainty, distress, or positive experiences. CONCLUSIONS: In a diverse population undergoing genetic counseling and multigene panel testing for hereditary cancer risk, the psychological response corresponded to test results and showed low distress and uncertainty. Further studies are needed to assess patient understanding and subsequent cancer screening among patients from diverse backgrounds.

Uptake and acceptability of a mainstreaming model of hereditary cancer multigene panel testing among patients with ovarian, pancreatic, and prostate cancer

“…This observation of higher MICRA-Uncertainty scores among patients with PV, reflecting greater uncertainty and concerns regarding cancer risk and the behavioral and interpersonal implications of these test results, is consistent with other studies that utilized this measure. 34 – 37 Interestingly, males with VUS also experienced slightly more uncertainty than females at this timepoint. Psychological experiences of men following receipt of MGPT 17 or VUS 38 are understudied.…”

Germline Pathogenic Variant Prevalence Among Latin American and US Hispanic Individuals Undergoing Testing for Hereditary Breast and Ovarian Cancer: A Cross-Sectional Study

“…A frequent concern with broader testing in populations of non-European ancestry, where testing is not common, is the high rate of VUS reported back to the ordering clinician. 69,70 Although VUS rates were higher in Latin America compared with US Hispanic individuals, this was not at the cost of diagnostic yield. Professional guidelines recommend that VUS do not provide a definitive molecular diagnosis and should not be used to inform clinical management.…”

Risk‐reducing mastectomy decisions among women with mutations in high‐ and moderate‐ penetrance breast cancer susceptibility genes

“…Culver et al recently published a prospective study of 1264 participants assessing psychosocial outcomes following genetic testing and reported that participants with high or moderate risk mutations had higher levels of uncertainty, distress, and concerns about their testing experience than participants who tested negative or had variants of uncertain significance. While these researchers demonstrated that moderate risk mutation carriers experience their genetic test results similarly to those with high‐risk mutations, those with high‐risk mutations understood options for cancer screening and prevention better than the moderate risk group (Culver, 2021). In addition, evolving evidence supporting moderate risk genes may result in patients receiving conflicting interpretations of their results and estimated risks (Hamilton & Robson, 2019).…”