How should we address the inevitable harms from non-negligent variant reclassification in predictive genetic testing?

The process of interpreting genetic variants, in which experts use all available evidence to determine whether an identified variant is associated with a current or future disease, is both scientific and nevertheless subjective. In this paper, we summarize the existing evidence that any given variant could be reclassified and that such a reclassification could lead to harm. Furthermore, the racial gap in genetic databases could lead to a higher likelihood of harm for non-white patients. We also review recent legal analyses indicating it is unlikely that an individual who sues for restitution would be successful, especially in the absence of evidence of lab negligence. We then propose a compensation program for medical genetic tests to ensure that individuals who experience demonstrable harm due to a variant reclassification can be made whole financially. We conclude by discussing outstanding questions that must be answered for such a program to be feasible.

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

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. LAY SUMMARY: Multigene panel tests for hereditary cancer have become widespread despite concerns about adverse psychological reactions among carriers of moderate-risk pathogenic variants (mutations) and among carriers of variants of uncertain significance. This large study of an ethnically and economically diverse cohort of patients undergoing panel testing found that 92% "never," "rarely," or only "sometimes" reacted negatively to results. Somewhat higher uncertainty and distress were identified among carriers of high- and moderate-risk pathogenic variants, and lower levels were identified among those with a variant of uncertain significance or a negative result. Although the psychological response corresponded to risk, reactions to testing were favorable, regardless of results.

Genetic Counselor and Healthcare Interpreter Perspectives on the Role of Interpreters in Cancer Genetic Counseling.

Cancer genetic counseling (CGC) combines psychosocial counseling and genetic education provided by genetic counselors to patients and families who have a history of cancer and are considering or have undergone genetic testing for hereditary cancer syndromes. The quantity and complexity of information provided can be challenging for any patient, but is even more so for those with limited English proficiency (LEP). This exploratory study investigated healthcare interpreters' and genetic counselors' perspectives on the role of interpreters in providing care to LEP patients during CGC. Through a survey of 18 interpreters and conventional content analysis of semi-structured interviews with 11 interpreters and 10 GCs at two California public hospitals, we found that: 1) interpreters viewed their role as patient advocate, cultural broker, and emotional support, not simply a conduit; 2) interpreters were challenged by remote interpretation, lack of genetic knowledge, and the emotional content of encounters; 3) interpreters and GCs held conflicting views of the value of counselors' limited Spanish knowledge; and 4) trust, the foundation of the interpreter-provider dyad, was often lacking. The challenges identified here may result in poor healthcare experiences and outcomes for LEP patients. As genomics becomes more widespread and more LEP patients encounter CGC, the role of healthcare interpreters in facilitating effective communication must be further defined in order to facilitate better working relationships between interpreters and genetic counselors, and optimal communication experiences for patients.

Patient communication of cancer genetic test results in a diverse population.

Research on the communication of genetic test results has focused predominately on non-Hispanic White (NHW) mutation-positive families with high-risk hereditary cancer conditions. Little is known about this process for racially and ethnically diverse individuals or for those with mutations in moderate risk genes. The communication behaviors of study participants who carry a gene mutation were analyzed 3 months after disclosure of genetic test results. Participants were queried about communication of their results, as part of a prospective study of multi-gene panel genetic testing. The responses of particpants who tested positive were analyzed by race/ethnicity and by level of cancer risk (high vs. moderate). Of the 216 mutation-positive study participants, 136 (63%) responded. Self-reported race/ethnicity was 46% NHW, 41% Hispanic, 10% Asian, and 2% Black. The majority (99.0%, n = 135) had shared their results with someone and 96% had told a family member (n = 130). Hispanic respondents were less likely to have told a healthcare provider about their results than NHW (29% vs. 68%, p < .0001). Asian respondents were less likely than NHW to encourage family members to undergo testing (OR = 0.1, p = .03); but Asian family members were more likely to undergo testing (OR = 8.0, p = .03). There were no differences in communication between those with a mutation in a high- or moderate-risk gene. Three months post genetic testing, communication of results was very high; 30% reported a family member underwent genetic testing. Further studies are needed to better understand the communication process in individuals from diverse racial/ethnic backgrounds.