Dataset Information

Uptake and acceptability of a mainstreaming model of hereditary cancer multigene panel testing among patients with ovarian, pancreatic, and prostate cancer.

ABSTRACT:

Purpose

To address demands for timely germline information to guide treatments, we evaluated experiences of patients with ovarian, pancreatic, and prostate cancer with a mainstreaming genetic testing model wherein multigene panel testing was ordered by oncologists with standardized pretest patient education, and genetic counselors delivered results and post-test genetic counseling via telephone.

Methods

Among 1,203 eligible patients, we conducted a prospective single-arm study to examine patient uptake and acceptability (via self-report surveys at baseline and three weeks and three months following result return) of this mainstreaming model.

Results

Only 10% of eligible patients declined participation. Among 1,054 tested participants, 10% had pathogenic variants (PV), 16% had variants of uncertain significance (VUS), and 74% had no variant identified (NV). Participants reported high initial acceptability, including high satisfaction with their testing decision. Variability over time in several outcomes existed for participants with PV or NV: those with NV experienced a temporary increase in depression (p_Time < 0.001; p_Time2 < 0.001), and those with PV experienced a small increase in genetic testing distress (p = 0.03). Findings suggested that result type, sex, and cancer type were also associated with outcomes including clinical depression and uncertainty.

Conclusion

This mainstreaming model may offer a feasible approach for extending access to germline genetic information.

SUBMITTER: Hamilton JG

PROVIDER: S-EPMC8556289 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background. Expansion of routine genetic testing for hereditary breast and ovarian cancer from conventional BRCA testing to a multigene test could improve diagnostic yield and increase the opportunity for cancer prevention in both identified carriers and their relatives. We use an economic decision model to assess whether the current knowledge on non-BRCA mutation prevalence, cancer risk, and patient preferences justifies switching to a multigene panel for testing of early-onset breast cancer patients. Methods. We evaluated routine testing by BRCA testing, a 7-gene panel, and a 14-gene panel using individual-level simulations of annual health state transitions over a lifetime perspective. Breast and ovarian cancer incidence is reduced and posttreatment survival is improved when high-risk mutations are detected and risk-reducing treatment offered. Most model inputs were synthesized from published literature. Intermediate health outcomes included breast and ovarian cancer incidence rates, along with organ-specific cancer mortality. Cost-effectiveness outcomes were health sector costs and quality-adjusted life years. Results. Intermediate health outcomes improved by testing with multigene panels. At a cost-effectiveness threshold of $77,000, a 7-gene panel test with five non-BRCA genes was the optimal strategy with an incremental cost-effectiveness ratio of $53,310 per quality-adjusted life year compared to BRCA-only testing. Limitations. Unable to stratify carriers to specific mutations within genes, we can only make predictions on the gene level, with combined risk estimates for known variants. As mutation prevalence is the absolute upper bound of returns to more expansive testing, the rarity of modelled mutations makes analysis outcomes sensitive to model implementation. Conclusions. A 7-gene panel to diagnose hereditary breast and ovarian cancer in early-onset breast cancer patients can be a cost-effective alternative to current BRCA-only testing in Norway.

Project description:Recent advances in next generation sequencing have enabled panel gene testing, or simultaneous testing for mutations in multiple genes for a clinical condition. With more extensive and widespread genetic testing, there will be increased detection of genes with moderate penetrance without established clinical guidelines and of variants of uncertain significance (VUS), or genetic variants unknown to either be disease-causing or benign. This study surveyed 232 patients who underwent genetic counseling for hereditary breast and ovarian cancer to examine the impact of panel gene testing on psychological outcomes, patient understanding, and utilization of genetic information. The survey used standardized instruments including the Impact of Event Scale (IES), Multidimensional Impact of Cancer Risk Assessment (MICRA), Satisfaction with Decision Instrument (SWD), Ambiguity Tolerance Scale (AT-20), genetics knowledge, and utilization of genetic test results. Study results suggested that unaffected individuals with a family history of breast or ovarian cancer who received positive results were most significantly impacted by intrusive thoughts, avoidance, and distress. However, scores were also modestly elevated among unaffected patients with a family history of breast and ovarian cancer who received VUS, highlighting the impact of ambiguous results that are frequent among patients undergoing genetic testing with large panels of genes. Potential risk factors for increased genetic testing-specific distress in this study included younger age, black or African American race, Hispanic origin, lower education level, and lower genetic knowledge and highlight the need for developing strategies to provide effective counseling and education to these communities, particularly when genetic testing utilizes gene panels that more commonly return VUS. More detailed pre-test education and counseling may help patients appreciate the probability of various types of test results and how results would be used clinically, and allow them to make more informed decisions about the type of genetic testing to select.