A Modern Dilemma: How Experts Grapple with Ambiguous Genetic Test Results

Abstract

Objective. Clinicians regularly use panel genetic testing to identify hereditary breast cancer risk, but this practice increases the rate of receiving an ambiguous test result, the variant of uncertain significance (VUS). VUS results are a growing and long-term challenge for providers and have caused negative patient outcomes. The objective of this study was to elicit expert opinions about patients’ decision making after receiving a VUS result to provide future guidance for VUS disclosure. Methods. Using an adapted mental models approach, experts ( N = 25) completed an online survey and in-depth interview eliciting qualitative judgments of the factors relevant to informed patient decision making after receiving a VUS result. Content analysis of interview transcripts clarified the basis for these judgments. Results. Participants identified 11 decisions facing patients after receiving VUS results grouped into ambiguity management or risk management. The experts also identified 24 factors relevant to each decision, which reflected 2 themes: objective factors (e.g., clinical information, guidelines) and psychosocial factors (e.g., understanding or risk perception). Conclusion. This study presents an adaptation of the mental models approach for communication under conditions of ambiguity. Findings suggest providers who present VUS results from genetic testing for hereditary breast cancer should discuss decisions related to ambiguity management that focus on hope for future reclassification, and be directive when discussing risk management decisions. Objective and psychosocial factors should influence both ambiguity and risk management decisions, but especially risk management decisions.

Views of Israeli healthcare professionals regarding communication of genetic variants of uncertain significance to patients

“…(2020) recently found that strategies used by genetic counselors to communicate uncertainty regarding genetic testing results included three core themes: being open and honest, adapting to patients’ needs, and focusing on what is known. Another recent study found that HCP's address VUSs with breast cancer patients through 2 main categories: ambiguity and risk management (Scherr et al., 2020). Ambiguity management included, for example, discussing the opportunity to participate in research studies, clinical DNA banking, expanded genetic testing, additional clinical evaluations, and maintaining contact with the provider who ordered the test.…”

“…Such a narrative demonstrates the customization of specific variants through a plot that begins with a mystery, develops through clinical discussions and research analyses, and hopefully ends with a resolution of the causal ambiguity (or not, in this case). It should remind us that providing the patient with an action they could take based on the VUS, which may be recommended for reducing ambiguity (Scherr et al., 2020), does not always correspond with a beneficial coping strategy.…”

“…HCPs must negotiate the expectations of patients, including negotiating how communication of uncertainty affects patients’ perceptions of the HCPs' credibility (Zhong et al., 2020). Furthermore, studying communication strategies of VUS disclosure has important implications for how genetic counselors can help facilitate meaning‐making for patients (Scherr et al., 2020). This study seeks to examine HCPs' communication methods and challenges regarding the disclosure of VUSs in clinical care, a topic which we still know relatively little of and, as a result of its recent introduction into practice, does not have clear professional guidelines.…”