Next-Generation Testing for Cancer Risk: Perceptions, Experiences, and Needs Among Early Adopters in Community Healthcare Settings

Abstract

Background: Advances in next-generation sequencing (NGS) technologies are driving a shift from single-gene to multigene panel testing for clinical genetic cancer risk assessment (GCRA). This study explored perceptions, experiences, and challenges with NGS testing for GCRA among U.S. community-based clinicians.

Methods: Surveys delivered at initial and 8-month time points, and 12-month tracking of cases presented in a multidisciplinary web-based case conference series, were conducted with GCRA providers who participated in a 235-member nationwide community of practice.

Results: The proportion of respondents ordering panel tests rose from 29% at initial survey (27/94) to 44% (46/107) within 8 months. Respondents reported significantly less confidence about interpreting and counseling about NGS compared with single-gene test results (p < 0.0001 for all comparisons). The most cited reasons for not ordering NGS tests included concerns about clinical utility, interpreting and communicating results, and lack of knowledge/skills. Multigene panels were used in 204/668 cases presented during 2013, yielding 37 (18%) deleterious (7% in low/moderate-penetrance genes), 88 (43%) with ≥1 variant of uncertain significance, 77 (38%) uninformative negative, and 2 (1%) inconclusive results.

Conclusions: Despite concerns about utility and ability to interpret/counsel about NGS results, a rapidly increasing uptake of NGS testing among community clinicians was documented. Challenges identified in case discussions point to the need for ongoing education, practice-based support, and opportunities to partner in research that contributes to characterization of lesser known genes.

FIG. 1.

Uptake of multigene panel testing. The number of Clinical Cancer Genetics Community of Practice (CCGCoP) survey respondents who ordered one or more multigene panel tests increased significantly between July, 2012 (29%; 27/94), and March, 2013 (44%; 46/107) (p = 0.021). There was no increase in the number of WES or whole genome tests ordered over this time frame (p > 0.05). WES, whole exome.

FIG. 2.

Case scenario responses. Responses to the hypothetical case scenario question, “Would you offer a multigene panel test for a BRCA-negative female who was diagnosed as having triple-negative breast cancer at age 34 and has a strong family history of breast cancer?” Initial survey respondents were significantly more likely to offer testing only on a research basis, while second survey respondents were more likely to offer testing if covered by insurance (p = 0.002).

FIG. 3.

Clinician self-efficacy with interpreting and counseling about different types of genetic test results. Overall scores demonstrated a high level of confidence with interpreting/counseling about single-gene results, and significantly less confidence (in descending order) about variants of uncertain significance (VUSs), multigene panel, and WES/whole genome test results (p < 0.001 for all comparisons). By-discipline comparisons revealed no significant differences in interpreting/counseling about single-gene results; GCs had more confidence than MDs and APNs/PAs with interpreting/counseling about VUSs (p = 0.003); MDs and GCs had greater confidence than APNs/PAs with interpreting/counseling about multigene panel and WES/WGS results (p < 0.001 for all comparisons). WGS, whole genome sequence.

FIG. 4.

Summary of multigene panel results presented during case conferencing. Two hundred four commercial multigene panel tests were presented by community clinicians during web-based case conferences from January 1, 2013, through January 1, 2014. Twelve additional tests were ordered, but cancelled due to denial for insurance coverage.