Variant of Uncertain Significance-Related Uncertainty in Breast Cancer Genomics

Purpose of Review: This paper considers the psychosocial implications of variant of uncertain significance (VUS)-derived uncertainty from the perspective of patients and providers and identifies potential uncertainty management strategies that can improve VUS-related clinical care. Recent Findings: Based on the analysis of current research evidence around VUS-related medical management as well as provider and patient experiences of VUS-related uncertainty, we conclude that uncertainty around this new type of medical information is pervasive. Uncertainty appraisal varies across different contextual and situational factors—individual’s cancer diagnosis, provider’s experience with VUS, gene in which VUS has been identified, etc. Most importantly, strategies for uncertainty management that can address much of the VUS-related uncertainty also exist and offer hope for the thousands of VUS that will be returned to patients in genomic medicine clinics. Summary: Uncertain sequencing results, when explained and relayed by experts in the presence of appropriate VUS-related reclassification and re-contact guidelines, increase the likelihood of maximal clinical and psychosocial benefit for patients without causing undue harm.