The Cost-Effectiveness of Multigene Panel Testing for Hereditary Breast and Ovarian Cancer in Norway

Abstract

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.

Guidance for the Harmonisation and Improvement of Economic Evaluations of Personalised Medicine

“…When including patient and clinician compliance in economic evaluations, confirm that the assumed compliance is accurate in the setting of interest and consider possible variation in compliance across societal groups.

Box 4 Incorporating compliance [ 56 ]

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Impact of changing guidelines on genetic testing and surveillance recommendations in a contemporary cohort of breast cancer survivors with family history of pancreatic cancer

“…Clinical caution in adopting multi-gene panel tests centered primarily on concerns about variants of uncertain significance, and lack of well-characterized risk information and management strategies for several of the low or moderate risk genes included in panels 38 , 39 . Additionally, questions about cost effectiveness 40 have been addressed over time 41 , 42 allowing insurers to adjust coverage criteria. Multiple studies have now documented additional relevant PGV findings in women with breast cancer offered multi-gene panel testing 43 – 46 .…”

The role of genomics in global cancer prevention

“…Before the 2010s, in settings where clinical cancer genetics services were available, risk assessment frequently included multiple rounds of single-gene testing with long turnaround times, and were therefore costly 66,67 . In the USA, and increasingly in other HICs, multigene panel testing (MGPT) has now become the standard procedure in clinical cancer genetic assessments, in part owing to its cost effectiveness, speed and efficiency [68][69][70][71][72][73][74] . Since the incorporation of MGPT into clinical practice in 2012, technological advances, including improvements in the bioinformatics pipelines for variant calling and interpretation, have been rapid and costs have decreased substantially 67,75 .…”