Dataset Information

Clinical testing of BRCA1 and BRCA2: a worldwide snapshot of technological practices.

ABSTRACT: Clinical testing of BRCA1 and BRCA2 began over 20 years ago. With the expiration and overturning of the BRCA patents, limitations on which laboratories could offer commercial testing were lifted. These legal changes occurred approximately the same time as the widespread adoption of massively parallel sequencing (MPS) technologies. Little is known about how these changes impacted laboratory practices for detecting genetic alterations in hereditary breast and ovarian cancer genes. Therefore, we sought to examine current laboratory genetic testing practices for BRCA1/BRCA2. We employed an online survey of 65 questions covering four areas: laboratory characteristics, details on technological methods, variant classification, and client-support information. Eight United States (US) laboratories and 78 non-US laboratories completed the survey. Most laboratories (93%; 80/86) used MPS platforms to identify variants. Laboratories differed widely on: (1) technologies used for large rearrangement detection; (2) criteria for minimum read depths; (3) non-coding regions sequenced; (4) variant classification criteria and approaches; (5) testing volume ranging from 2 to 2.5 × 10⁵ tests annually; and (6) deposition of variants into public databases. These data may be useful for national and international agencies to set recommendations for quality standards for BRCA1/BRCA2 clinical testing. These standards could also be applied to testing of other disease genes.

SUBMITTER: Toland AE

PROVIDER: S-EPMC5814433 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Clinical testing of BRCA1 and BRCA2: a worldwide snapshot of technological practices.

Toland Amanda Ewart AE Forman Andrea A Couch Fergus J FJ Culver Julie O JO Eccles Diana M DM Foulkes William D WD Hogervorst Frans B L FBL Houdayer Claude C Levy-Lahad Ephrat E Monteiro Alvaro N AN Neuhausen Susan L SL Plon Sharon E SE Sharan Shyam K SK Spurdle Amanda B AB Szabo Csilla C Brody Lawrence C LC

NPJ genomic medicine 20180215

Clinical testing of BRCA1 and BRCA2 began over 20 years ago. With the expiration and overturning of the BRCA patents, limitations on which laboratories could offer commercial testing were lifted. These legal changes occurred approximately the same time as the widespread adoption of massively parallel sequencing (MPS) technologies. Little is known about how these changes impacted laboratory practices for detecting genetic alterations in hereditary breast and ovarian cancer ge ...[more]

PMID: 29479477

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Project description:ImportanceBRCA testing is recommended for young women diagnosed as having breast cancer, but little is known about decisions surrounding testing and how results may influence treatment decisions in young patients.ObjectivesTo describe the use of BRCA testing and to evaluate how concerns about genetic risk and use of genetic information affect subsequent treatment decisions in young women with breast cancer.Design, setting, and participantsCross-sectional analysis of data collected following the opening of the study to accrual from October 10, 2006, through December 31, 2014, as part of the Helping Ourselves, Helping Others: Young Women's Breast Cancer Study, an ongoing prospective cohort study. Study participants included 897 women aged 40 years and younger at breast cancer diagnosis from 11 academic and community medical centers.Main outcomes and measuresFrequency and trends in the use of BRCA testing and how genetic information is used to make treatment decisions among women who test positive vs negative for a BRCA mutation.ResultsA total of 780 (87.0%) of 897 women reported BRCA testing by 1 year after breast cancer diagnosis (mean age at diagnosis, 35.3 vs 36.9 years for untested women; P < .001), with the frequency of testing increasing among women diagnosed from August 1, 2006, through December 31, 2013. Of 39 women who were diagnosed as having breast cancer in 2006, 30 (76.9%) reported testing. In 2007, a slightly lower percentage of women (87 of 124 [70.2%]) reported testing; however, the proportion tested increased each subsequent year, with 141 (96.6%) of 146 and 123 (95.3%) of 129 women diagnosed as having breast cancer in 2012 and 2013, respectively, reporting BRCA testing (P < .001). Among untested women, 37 (31.6%) of 117 did not report discussion of the possibility that they might have a mutation with a physician and/or genetic counselor, and 43 (36.8%) of 117 were thinking of testing in the future. A total of 248 (29.8%) of 831 women said that knowledge or concern about genetic risk influenced treatment decisions; among these women, 76 (86.4%) of 88 mutation carriers and 82 (51.2%) of 160 noncarriers chose bilateral mastectomy (P < .001). Fewer women reported that systemic treatment decisions were influenced by genetic risk concern.Conclusions and relevanceRates of BRCA1 and BRCA2 mutation testing are increasing in young women with breast cancer. Given that knowledge and concern about genetic risk influence surgical decisions and may affect systemic therapy trial eligibility, all young women with breast cancer should be counseled and offered genetic testing, consistent with the National Comprehensive Cancer Network guidelines.

Project description:ImportancePopulation-based BRCA testing can identify many more BRCA carriers who will be missed by the current practice of BRCA testing based on family history (FH) and clinical criteria. These carriers can benefit from screening and prevention, potentially preventing many more breast and ovarian cancers and deaths than the current practice.ObjectiveTo estimate the incremental lifetime health outcomes, costs, and cost-effectiveness associated with population-based BRCA testing compared with FH-based testing in Canada.Design, setting, and participantsFor this economic evaluation, a Markov model was developed to compare the lifetime costs and outcomes of BRCA1/BRCA2 testing for all general population women aged 30 years compared with FH-based testing. BRCA carriers are offered risk-reducing salpingo-oophorectomy to reduce their ovarian cancer risk and magnetic resonance imaging (MRI) and mammography screening, medical prevention, and risk-reducing mastectomy to reduce their breast cancer risk. The analyses were conducted from both payer and societal perspectives. This study was conducted from October 1, 2022, to February 20, 2024.Main outcomes and measuresOutcomes of interest were ovarian cancer, breast cancer, additional heart disease deaths, and incremental cost-effectiveness ratio ICER per quality-adjusted life-year (QALY). One-way and probabilistic-sensitivity-analyses (PSA) were undertaken to explore the uncertainty.ResultsIn the simulated cohort of 1 000 000 women aged 30 years in Canada, the base case ICERs of population-based BRCA testing were CAD $32 276 (US $23 402.84) per QALY from the payer perspective or CAD $16 416 (US $11 903.00) per QALY from the societal perspective compared with FH-based testing, well below the established Canadian cost-effectiveness thresholds. Population testing remained cost-effective for ages 40 to 60 years but not at age 70 years. The results were robust for multiple scenarios, 1-way sensitivity, and PSA. More than 99% of simulations from payer and societal perspectives were cost-effective on PSA (5000 simulations) at the CAD $50 000 (US $36 254.25) per QALY willingness-to-pay threshold. Population-based BRCA testing could potentially prevent an additional 2555 breast cancers and 485 ovarian cancers in the Canadian population, corresponding to averting 196 breast cancer deaths and 163 ovarian cancer deaths per 1 000 000 population.Conclusions and relevanceIn this economic evaluation, population-based BRCA testing was cost-effective compared with FH-based testing in Canada from payer and societal perspectives. These findings suggest that changing the genetic testing paradigm to population-based testing could prevent thousands of breast and ovarian cancers.

Dataset Information

Clinical testing of BRCA1 and BRCA2: a worldwide snapshot of technological practices.

Publications

Clinical testing of <i>BRCA1</i> and <i>BRCA2</i>: a worldwide snapshot of technological practices.

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