A comprehensive genomic reporting structure for communicating all clinically significant primary and secondary findings.

Genomic sequencing (GS) can reveal secondary findings (SFs), findings unrelated to the reason for testing, that can be overwhelming to both patients and providers. An effective approach for communicating all clinically significant primary and secondary GS results is needed to effectively manage this large volume of results. The aim of this study was to develop a comprehensive approach to communicate all clinically significant primary and SF results. A genomic test report with accompanying patient and provider letters were developed in three phases: review of current clinical reporting practices, consulting with genetic and non-genetics experts, and iterative refinement through circulation to key stakeholders. The genomic test report and consultation letters present a myriad of clinically relevant GS results in distinct, tabulated sections, including primary (cancer) and secondary findings, with in-depth details of each finding generated from exome sequencing. They provide detailed variant and disease information, personal and familial risk assessments, clinical management details, and additional resources to help support providers and patients with implementing healthcare recommendations related to their GS results. The report and consultation letters represent a comprehensive approach to communicate all clinically significant SFs to patients and providers, facilitating clinical management of GS results.

Effectiveness of the Genomics ADvISER decision aid for the selection of secondary findings from genomic sequencing: a randomized clinical trial.

PURPOSE: To evaluate the effectiveness of the Genomics ADvISER (www.genomicsadviser.com) decision aid (DA) for selection of secondary findings (SF), compared with genetic counseling alone. METHODS: A randomized controlled trial (RCT) was conducted to evaluate whether the Genomics ADvISER is superior to genetic counseling when hypothetically selecting SF. Participants were randomized to use the DA followed by discussion with a genetic counselor, or to genetic counseling alone. Surveys were administered at baseline and post-intervention. Primary outcome was decisional conflict. Secondary outcomes were knowledge, preparation for, and satisfaction with decision-making, anxiety, and length of counseling session. RESULTS: Participants (n = 133) were predominantly White/European (74%), female (90%), and ≥50 years old (60%). Decisional conflict (mean difference 0.05; P = 0.60), preparation for decision-making (0.17; P = 0.95), satisfaction with decision (-2.18; P = 0.06), anxiety (0.72; P = 0.56), and knowledge of sequencing limitations (0.14; P = 0.70) did not significantly differ between groups. However, intervention participants had significantly higher knowledge of SF (0.39; P < 0.001) and sequencing benefits (0.97; P = 0.01), and significantly shorter counseling time (24.40 minutes less; P < 0.001) CONCLUSIONS: The Genomics ADvISER did not decrease decisional conflict but reduced counseling time and improved knowledge. This decision aid could serve as an educational tool, reducing in-clinic time and potentially health care costs.

An update on genetic risk assessment and prevention: the role of genetic testing panels in breast cancer.

Introduction: In the past 5 years, multi-gene panels have replaced the practice of BRCA1 and BRCA2 genetic testing in cases of suspected inherited breast cancer susceptibility. A variety of genes have been included on these panels without certainty of their clinical utility. Pertinent current and historical literature was reviewed to provide an up-to-date snapshot of the changing landscape of the use of gene panel tests in the context of breast cancer. Areas covered: Following a recent review of the evidence, 10 genes have been found to have definitive evidence of increased breast cancer risk with variable penetrance. Here, we review the recent changes to the practice of multi-gene panel use in breast cancer diagnoses, including an update on next generation sequencing, alternative models of genetic testing, considerations when ordering these panel tests, and recommendations for management in identified carriers for a variety of genes. A comparison of screening recommendations and carrier frequencies from recent studies is also explored. Lastly, we consider what the future of hereditary oncologic genetic testing holds. Expert opinion: The transition to multi-gene panels in breast cancer patients has improved the likelihood of capturing a rare variant in a well-established gene associated with hereditary breast cancer (e.g. BRCA1 and BRCA2, TP53). There is also an increase in the likelihood of uncovering an uncertain result. This could be in the form of a variant of uncertain significance, or a pathogenic variant in a gene with questionable breast cancer risk-association. Concurrently, a changing landscape of who orders genetic tests will improve access to genetic testing. This pervasiveness of genetic testing must be accompanied with increased genetic literacy in all health-care providers, and access to support from genetics professionals for management of patients and at-risk family members.

Development of patient "profiles" to tailor counseling for incidental genomic sequencing results.

Guidelines recommend that providers engage patients in shared decision-making about receiving incidental results (IR) prior to genomic sequencing (GS), but this can be time-consuming, given the myriad of IR and variation in patients' preferences. We aimed to develop patient profiles to inform pre-test counseling for IR. We conducted semi-structured interviews with participants as a part of a randomized trial of the GenomicsADvISER.com, a decision aid for selecting IR. Interviews explored factors participants considered when deliberating over learning IR. Interviews were analyzed by thematic analysis and constant comparison. Participants were mostly female (28/31) and about half of them were over the age of 50 (16/31). We identified five patient profiles that reflect common contextual factors, attitudes, concerns, and perceived utility of IR. Information Enthusiasts self-identified as "planners" and valued learning most or all IR to enable planning and disease prevention because "knowledge is power". Concerned Individuals defined themselves as "anxious," and were reluctant to learn IR, anticipating negative psychological impacts from IR. Contemplators were discerning about the value and limitations of IR, weighing health benefits with the impacts of not being able to "un-know" information. Individuals of Advanced Life Stage did not consider IR relevant for themselves and primarily considered their implications for family members. Reassurance Seekers were reassured by previous negative genetic test results which shaped their expectations for receiving no IR: "hopefully [GS will] be negative, too. And then I can rest easy". These profiles could inform targeted counseling for IR by providing a framework to address common values, concerns. and misconceptions.