Current detection rates and time-to-detection of all identifiable <i>BRCA</i> carriers in the Greater London population

Manchanda, Ranjit; Blyuss, Oleg; Gaba, Faiza; Gordeev, Vladimir Sergeevich; Jacobs, Chris; Burnell, Matthew; Gan, Carmen; Taylor, Rohan; Turnbull, Clare; Legood, Rosa; Zaikin, Alexey; Antoniou, Antonis C.; Menon, Usha; Jacobs, Ian

doi:10.1136/jmedgenet-2017-105195

Cited by 57 publications

(80 citation statements)

References 37 publications

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“…Why should we need to wait for this to happen? Despite over two decades of testing, only 3% of estimated carriers in the population have been identified . Limited public and health‐professional awareness, coupled with the complexity and inefficiencies of a gate‐keeper‐driven testing pathway/service structure has resulted in restricted access and under‐utilisation of genetic testing across all health systems .…”

Section: Introductionmentioning

confidence: 99%

“…Continuing at the current rates of identification, we will never identify even the 50% of the estimated residual pool of carriers in the population who fulfil testing criteria, let alone the unidentifiable half. Even doubling current rates will need ~165 years to identify these 50% of at‐risk individuals . Incorporation of mainstreaming into clinical practice will improve detection rates and identify those lacking a strong FH but still requires individuals to develop cancer before unaffected carriers can be identified.…”

Section: Introductionmentioning

confidence: 99%

“…Incorporation of mainstreaming into clinical practice will improve detection rates and identify those lacking a strong FH but still requires individuals to develop cancer before unaffected carriers can be identified. Forecasting models suggest that addition of mainstreaming to current testing rates will also require ~250 years to identify the entire residual pool of carriers . Given the huge benefit and opportunity to prevent cancers in unaffected mutation carriers, this questions the adequacy and satisfactoriness of our current clinical approach.…”

Section: Introductionmentioning

confidence: 99%

“…Despite over two decades of testing, only 3% of estimated carriers in the population have been identified. 4 Limited public and healthprofessional awareness, coupled with the complexity and inefficiencies of a gate-keeper-driven testing pathway/service structure has resulted in restricted access and underutilisation of genetic testing across all health systems. 5 Continuing at the current rates of identification, we will never identify even the 50% of the estimated residual pool of carriers in the population who fulfil testing criteria, let alone the unidentifiable half.…”

mentioning

confidence: 99%

“…Even doubling current rates will need~165 years to identify these 50% of at-risk individuals. 4 Incorporation of mainstreaming into clinical practice will improve detection rates and identify those lacking a strong FH but still requires individuals to develop cancer before unaffected carriers can be identified. Forecasting models suggest that addition of mainstreaming to current testing rates will also require~250 years to identify the entire residual pool of carriers.…”

mentioning

confidence: 99%

See 4 more Smart Citations

A commentary on population genetic testing for primary prevention: changing landscape and the need to change paradigm

Manchanda

Gaba

2019

BJOG

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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A commentary on population genetic testing for primary prevention: changing landscape and the need to change paradigm

Manchanda

Gaba

2019

BJOG

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Cost-Effectiveness of Gene-Specific Prevention Strategies for Ovarian and Breast Cancer

Wei,

Sun,

Slade

et al. 2024

JAMA Netw Open

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ImportancePathogenic variants (PVs) in BRCA1, BRCA2, PALB2, RAD51C, RAD51D, and BRIP1 cancer susceptibility genes (CSGs) confer an increased ovarian cancer (OC) risk, with BRCA1, BRCA2, PALB2, RAD51C, and RAD51D PVs also conferring an elevated breast cancer (BC) risk. Risk-reducing surgery, medical prevention, and BC surveillance offer the opportunity to prevent cancers and deaths, but their cost-effectiveness for individual CSGs remains poorly addressed.ObjectiveTo estimate the cost-effectiveness of prevention strategies for OC and BC among individuals carrying PVs in the previously listed CSGs.Design, Setting, and ParticipantsIn this economic evaluation, a decision-analytic Markov model evaluated the cost-effectiveness of risk-reducing salpingo-oophorectomy (RRSO) and, where relevant, risk-reducing mastectomy (RRM) compared with nonsurgical interventions (including BC surveillance and medical prevention for increased BC risk) from December 1, 2022, to August 31, 2023. The analysis took a UK payer perspective with a lifetime horizon. The simulated cohort consisted of women aged 30 years who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. Appropriate sensitivity and scenario analyses were performed.ExposuresCSG-specific interventions, including RRSO at age 35 to 50 years with or without BC surveillance and medical prevention (ie, tamoxifen or anastrozole) from age 30 or 40 years, RRM at age 30 to 40 years, both RRSO and RRM, BC surveillance and medical prevention, or no intervention.Main Outcomes and MeasuresThe incremental cost-effectiveness ratio (ICER) was calculated as incremental cost per quality-adjusted life-year (QALY) gained. OC and BC cases and deaths were estimated.ResultsIn the simulated cohort of women aged 30 years with no cancer, undergoing both RRSO and RRM was most cost-effective for individuals carrying BRCA1 (RRM at age 30 years; RRSO at age 35 years), BRCA2 (RRM at age 35 years; RRSO at age 40 years), and PALB2 (RRM at age 40 years; RRSO at age 45 years) PVs. The corresponding ICERs were −£1942/QALY (−$2680/QALY), −£89/QALY (−$123/QALY), and £2381/QALY ($3286/QALY), respectively. RRSO at age 45 years was cost-effective for RAD51C, RAD51D, and BRIP1 PV carriers compared with nonsurgical strategies. The corresponding ICERs were £962/QALY ($1328/QALY), £771/QALY ($1064/QALY), and £2355/QALY ($3250/QALY), respectively. The most cost-effective preventive strategy per 1000 PV carriers could prevent 923 OC and BC cases and 302 deaths among those carrying BRCA1; 686 OC and BC cases and 170 deaths for BRCA2; 464 OC and BC cases and 130 deaths for PALB2; 102 OC cases and 64 deaths for RAD51C; 118 OC cases and 76 deaths for RAD51D; and 55 OC cases and 37 deaths for BRIP1. Probabilistic sensitivity analysis indicated both RRSO and RRM were most cost-effective in 96.5%, 89.2%, and 84.8% of simulations for BRCA1, BRCA2, and PALB2 PVs, respectively, while RRSO was cost-effective in approximately 100% of simulations for RAD51C, RAD51D, and BRIP1 PVs.Conclusions and RelevanceIn this cost-effectiveness study, RRSO with or without RRM at varying optimal ages was cost-effective compared with nonsurgical strategies for individuals who carried BRCA1, BRCA2, PALB2, RAD51C, RAD51D, or BRIP1 PVs. These findings support personalizing risk-reducing surgery and guideline recommendations for individual CSG-specific OC and BC risk management.

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Economic Evaluation of Population-Based BRCA1 and BRCA2 Testing in Canada

Sun,

Wei,

Fierheller

et al. 2024

JAMA Netw Open

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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.

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Current detection rates and time-to-detection of all identifiable BRCA carriers in the Greater London population

Abstract: Background

Cited by 57 publications

References 37 publications

A commentary on population genetic testing for primary prevention: changing landscape and the need to change paradigm

A commentary on population genetic testing for primary prevention: changing landscape and the need to change paradigm

Cost-Effectiveness of Gene-Specific Prevention Strategies for Ovarian and Breast Cancer

Economic Evaluation of Population-Based BRCA1 and BRCA2 Testing in Canada

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