Dataset Information

Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients.

ABSTRACT:

Purpose

The aim of this study was to determine the clinical and molecular characteristics of 2,079 patients who underwent hereditary cancer multigene panel testing.

Methods

Panels included comprehensive analysis of 14-22 cancer susceptibility genes (BRCA1 and BRCA2 not included), depending on the panel ordered (BreastNext, OvaNext, ColoNext, or CancerNext). Next-generation sequencing and deletion/duplication analyses were performed for all genes except EPCAM (deletion/duplication analysis only). Clinical histories of ColoNext patients harboring mutations in genes with well-established diagnostic criteria were assessed to determine whether diagnostic/testing criteria were met.

Results

Positive rates were defined as the proportion of patients with a pathogenic mutation/likely pathogenic variant(s) and were as follows: 7.4% for BreastNext, 7.2% for OvaNext, 9.2% for ColoNext, and 9.6% for CancerNext. Inconclusive results were found in 19.8% of BreastNext, 25.6% of OvaNext, 15.1% of ColoNext, and 23.5% of CancerNext tests. Based on information submitted by clinicians, 30% of ColoNext patients with mutations in genes with well-established diagnostic criteria did not meet corresponding criteria.

Conclusion

Our data point to an important role for targeted multigene panels in diagnosing hereditary cancer predisposition, particularly for patients with clinical histories spanning several possible diagnoses and for patients with suspicious clinical histories not meeting diagnostic criteria for a specific hereditary cancer syndrome.

SUBMITTER: LaDuca H

PROVIDER: S-EPMC4225457 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Publications

Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients.

LaDuca Holly H Stuenkel A J AJ Dolinsky Jill S JS Keiles Steven S Tandy Stephany S Pesaran Tina T Chen Elaine E Gau Chia-Ling CL Palmaer Erika E Shoaepour Kamelia K Shah Divya D Speare Virginia V Gandomi Stephanie S Chao Elizabeth E

Genetics in medicine : official journal of the American College of Medical Genetics 20140424 11

<h4>Purpose</h4>The aim of this study was to determine the clinical and molecular characteristics of 2,079 patients who underwent hereditary cancer multigene panel testing.<h4>Methods</h4>Panels included comprehensive analysis of 14-22 cancer susceptibility genes (BRCA1 and BRCA2 not included), depending on the panel ordered (BreastNext, OvaNext, ColoNext, or CancerNext). Next-generation sequencing and deletion/duplication analyses were performed for all genes except EPCAM (deletion/duplication ...[more]

PMID: 24763289

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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.

Dataset Information

Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients.

Purpose

Methods

Results

Conclusion

Publications

Utilization of multigene panels in hereditary cancer predisposition testing: analysis of more than 2,000 patients.

Similar Datasets

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