Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Cost-effectiveness of Universal BRCA1/2 Screening: Evidence-Based Decision Making

Cost-effectiveness of Universal BRCA1/2 Screening: Evidence-Based Decision Making Of the 233 000 breast cancers diagnosed annually in the United States, 5% to 10% are attributable to mutations in the BRCA1 or BRCA2 genes.1 Breast cancers in BRCA mutation carriers are characterized by younger age at onset, bilateral occurrence, and more aggressive subtypes, such as “triple-negative.”1 Female mutation carriers face a 45% to 65% breast cancer risk by age 70 years, and an ovarian cancer risk ranging from 10% to 17% (BRCA2) to 39% (BRCA1). Women found to be BRCA mutation carriers—either through genetic screening or following a cancer diagnosis—may choose to undergo bilateral risk-reducing mastectomy (RRM) and/or salpingo-oophorectomy (RRSO) as an alternative to increased surveillance or chemoprevention. Knowledge of a genetic mutation may have a further impact on fertility decisions, including oocyte retrieval and genetic testing prior to cryopreservation or embryo implantation. Although the US Preventive Services Task Force advises BRCA genetic testing only for women with a known familial history of breast, ovarian, tubal, or peritoneal cancer, a recent Viewpoint in JAMA2 called for universal BRCA testing of all women older than 30 years in the United States. One factor influencing this recommendation is that more than half of all women with BRCA mutations have no family history of breast cancer.2,3 Although the announcement of a $249 genetic test offered by Color Genomics may induce more price competition, given the extraordinarily low prevalence of BRCA mutations, the potential value of population-based genetic testing is questionable. Decision-analytic modeling is an established technique for estimating the potential costs and health benefits of population-based screening strategies. These models are especially useful for capturing a sequence of probabilities: proportion of women with a BRCA mutation, fraction of mutation carriers who elect RRM and/or RRSO, and conditional likelihood of breast or ovarian cancer with and without RRM or RRSO. Using a prior model (eFigure in the Supplement)3 updated with current treatment costs for the United States (eTable 1 in the Supplement),4 we estimated the cost-effectiveness of universal BRCA testing of all US women older than 30 years, and the potential number of cancers prevented and life-years saved (eTable 2 in the Supplement). Assuming that 1 in 400 women carry a BRCA mutation, the cost-effectiveness of universal screening with Myriad’s test exceeds $1.7 million per quality-adjusted life year (QALY) gained, compared with testing only women with a familial history of breast cancer. Ambry Genetics’ slightly cheaper test still generates a cost-effectiveness ratio of more than $900 000 per QALY gained. In contrast, screening women of Ashkenazi Jewish descent—among whom 1 out of every 50 women carries a mutation—generates cost savings with Myriad’s less expensive test for 3 founder mutations. Another study3 has shown similarly favorable cost-effectiveness estimates for this population in the United Kingdom. Universal BRCA screening could avert an additional 4 breast cancers and 2 ovarian cancers per 10 000 women screened compared with family history–based screening. This generates an additional 0.006 years of life expectancy, or 2.1 additional days, on average. For 99.75% of women screened, a negative genetic test result offers no gain in life expectancy, does not eliminate the need for regular mammograms, and may provide false reassurance. For the 0.25% with a BRCA mutation, universal screening extends life expectancy by 3.5 years vs family history-based screening, a relatively modest gain, because many women found to have a deleterious mutation opt for risk-reducing surgery, increased surveillance, or both. With population-level screening of only Jewish women, 62 breast and 34 ovarian cancers per 10 000 women are averted, and average gains in life expectancy are 16-fold higher than with universal screening because a larger fraction of women are identified as BRCA mutation carriers. Other diagnostic techniques for breast cancer generate significantly more value for their cost (Table). Annual mammography for BRCA carriers costs less than $30 000 per QALY gained.5 Augmenting mammography with magnetic resonance imaging costs less than $180 000 per QALY gained,5,7 with superior cost-effectiveness in BRCA1 carriers vs BRCA2.5 Biennial mammograms for 40- to 49-year-old women with high breast density (Breast Imaging–Reporting and Data System [BI-RADS] categories 3-4), and therefore higher 10-year incidence of breast cancer, generate cost-effectiveness values of $75 000 to $89 000 per QALY gained.6 Among women with less dense breasts, biennial mammograms cost $140 000 (BI-RADS category 2) to $363 000 (BI-RADS category 1) per QALY gained,6 far less than universal BRCA genetic testing with Myriad or Ambry. Table. Cost-effectivenessa of Breast Cancer Testing Strategies in the United States View LargeDownload Is it possible for population-level BRCA screening to be cost-effective? Even if every woman with a detected mutation elects to have RRM and RRSO, universal screening still exceeds $1 million per QALY gained. We initially assumed that RRSO reduces ovarian cancer risk by 96%; RRSO alone halves breast cancer risk; RRM alone reduces breast cancer risk by 91%; and both procedures reduce breast cancer risk by 95%.3 Under the optimistic assumption that risk-reducing surgery completely eliminates cancer risk, universal BRCA screening still exceeds $970 000 per QALY gained compared with screening based on family history. If the price of BRCA genetic testing falls below $250 as indicated by Color Genomics, cost-effectiveness dramatically improves to $53 000 per QALY gained, far below the oft-cited $100 000 acceptable cost-effectiveness threshold based on hemodialysis treatment for end-stage renal disease. Given the potential market size of women interested in testing for BRCA and other genes, a drastically lower test price could simultaneously increase test utilization and profitability. Bundling BRCA testing with other cancer-associated genes, such as p53 or PALB2, could further improve cost-effectiveness estimates, although more information is needed about the long-term risks of cancer associated with such rare mutations. The logistics of genetically testing more than 100 million women pose additional challenges and would likely overwhelm the capacity of existing genetic counselors. Asking primary care physicians to counsel and test patients would further tax overburdened clinicians, so other avenues, such as mail-order testing and online counseling, would need to be explored. Before a broad genetic testing program in the United States is realistically considered, understanding the relative value of such a program is important, especially because these resources may offer more health benefits if spent on earlier or more frequent breast imaging. Even though a very small percentage of women would benefit from universal BRCA testing, at $2000 to $4000 per test, such a strategy is an inefficient use of health care resources. Back to top Article Information Corresponding Author: Elisa F. Long, PhD, UCLA Anderson School of Management, 110 Westwood Plaza, Ste B508, Los Angeles, CA 90095 (elisa.long@anderson.ucla.edu). Published Online: September 3, 2015. doi:10.1001/jamaoncol.2015.2340. Conflict of Interest Disclosures: None reported. Additional Contributions: Dr Ganz is currently on the Advisory Board for InformedDNA. References 1. US Breast Cancer Statistics. 2014; http://www.breastcancer.org/symptoms/understand_bc/statistics. Accessed July 13, 2015. 2. King MC, Levy-Lahad E, Lahad A. Population-based screening for BRCA1 and BRCA2: 2014 Lasker Award. JAMA. 2014;312(11):1091-1092.PubMedGoogle ScholarCrossref 3. Manchanda R, Legood R, Burnell M, et al. Cost-effectiveness of population screening for BRCA mutations in Ashkenazi Jewish women compared with family history-based testing. J Natl Cancer Inst. 2015;107(1):380.PubMedGoogle ScholarCrossref 4. Grann VR, Patel PR, Jacobson JS, et al. Comparative effectiveness of screening and prevention strategies among BRCA1/2-affected mutation carriers. Breast Cancer Res Treat. 2011;125(3):837-847.PubMedGoogle ScholarCrossref 5. Plevritis SK, Kurian AW, Sigal BM, et al. Cost-effectiveness of screening BRCA1/2 mutation carriers with breast magnetic resonance imaging. JAMA. 2006;295(20):2374-2384.PubMedGoogle ScholarCrossref 6. Schousboe JT, Kerlikowske K, Loh A, Cummings SR. Personalizing mammography by breast density and other risk factors for breast cancer: analysis of health benefits and cost-effectiveness. Ann Intern Med. 2011;155(1):10-20.PubMedGoogle ScholarCrossref 7. Moore SG, Shenoy PJ, Fanucchi L, Tumeh JW, Flowers CR. Cost-effectiveness of MRI compared to mammography for breast cancer screening in a high risk population. BMC Health Serv Res. 2009;9:9.PubMedGoogle ScholarCrossref http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png JAMA Oncology American Medical Association

Cost-effectiveness of Universal BRCA1/2 Screening: Evidence-Based Decision Making

JAMA Oncology , Volume 1 (9) – Dec 1, 2015

Loading next page...
 
/lp/american-medical-association/cost-effectiveness-of-universal-brca1-2-screening-evidence-based-00gU67pVPB
Publisher
American Medical Association
Copyright
Copyright © 2015 American Medical Association. All Rights Reserved.
ISSN
2374-2437
eISSN
2374-2445
DOI
10.1001/jamaoncol.2015.2340
Publisher site
See Article on Publisher Site

Abstract

Of the 233 000 breast cancers diagnosed annually in the United States, 5% to 10% are attributable to mutations in the BRCA1 or BRCA2 genes.1 Breast cancers in BRCA mutation carriers are characterized by younger age at onset, bilateral occurrence, and more aggressive subtypes, such as “triple-negative.”1 Female mutation carriers face a 45% to 65% breast cancer risk by age 70 years, and an ovarian cancer risk ranging from 10% to 17% (BRCA2) to 39% (BRCA1). Women found to be BRCA mutation carriers—either through genetic screening or following a cancer diagnosis—may choose to undergo bilateral risk-reducing mastectomy (RRM) and/or salpingo-oophorectomy (RRSO) as an alternative to increased surveillance or chemoprevention. Knowledge of a genetic mutation may have a further impact on fertility decisions, including oocyte retrieval and genetic testing prior to cryopreservation or embryo implantation. Although the US Preventive Services Task Force advises BRCA genetic testing only for women with a known familial history of breast, ovarian, tubal, or peritoneal cancer, a recent Viewpoint in JAMA2 called for universal BRCA testing of all women older than 30 years in the United States. One factor influencing this recommendation is that more than half of all women with BRCA mutations have no family history of breast cancer.2,3 Although the announcement of a $249 genetic test offered by Color Genomics may induce more price competition, given the extraordinarily low prevalence of BRCA mutations, the potential value of population-based genetic testing is questionable. Decision-analytic modeling is an established technique for estimating the potential costs and health benefits of population-based screening strategies. These models are especially useful for capturing a sequence of probabilities: proportion of women with a BRCA mutation, fraction of mutation carriers who elect RRM and/or RRSO, and conditional likelihood of breast or ovarian cancer with and without RRM or RRSO. Using a prior model (eFigure in the Supplement)3 updated with current treatment costs for the United States (eTable 1 in the Supplement),4 we estimated the cost-effectiveness of universal BRCA testing of all US women older than 30 years, and the potential number of cancers prevented and life-years saved (eTable 2 in the Supplement). Assuming that 1 in 400 women carry a BRCA mutation, the cost-effectiveness of universal screening with Myriad’s test exceeds $1.7 million per quality-adjusted life year (QALY) gained, compared with testing only women with a familial history of breast cancer. Ambry Genetics’ slightly cheaper test still generates a cost-effectiveness ratio of more than $900 000 per QALY gained. In contrast, screening women of Ashkenazi Jewish descent—among whom 1 out of every 50 women carries a mutation—generates cost savings with Myriad’s less expensive test for 3 founder mutations. Another study3 has shown similarly favorable cost-effectiveness estimates for this population in the United Kingdom. Universal BRCA screening could avert an additional 4 breast cancers and 2 ovarian cancers per 10 000 women screened compared with family history–based screening. This generates an additional 0.006 years of life expectancy, or 2.1 additional days, on average. For 99.75% of women screened, a negative genetic test result offers no gain in life expectancy, does not eliminate the need for regular mammograms, and may provide false reassurance. For the 0.25% with a BRCA mutation, universal screening extends life expectancy by 3.5 years vs family history-based screening, a relatively modest gain, because many women found to have a deleterious mutation opt for risk-reducing surgery, increased surveillance, or both. With population-level screening of only Jewish women, 62 breast and 34 ovarian cancers per 10 000 women are averted, and average gains in life expectancy are 16-fold higher than with universal screening because a larger fraction of women are identified as BRCA mutation carriers. Other diagnostic techniques for breast cancer generate significantly more value for their cost (Table). Annual mammography for BRCA carriers costs less than $30 000 per QALY gained.5 Augmenting mammography with magnetic resonance imaging costs less than $180 000 per QALY gained,5,7 with superior cost-effectiveness in BRCA1 carriers vs BRCA2.5 Biennial mammograms for 40- to 49-year-old women with high breast density (Breast Imaging–Reporting and Data System [BI-RADS] categories 3-4), and therefore higher 10-year incidence of breast cancer, generate cost-effectiveness values of $75 000 to $89 000 per QALY gained.6 Among women with less dense breasts, biennial mammograms cost $140 000 (BI-RADS category 2) to $363 000 (BI-RADS category 1) per QALY gained,6 far less than universal BRCA genetic testing with Myriad or Ambry. Table. Cost-effectivenessa of Breast Cancer Testing Strategies in the United States View LargeDownload Is it possible for population-level BRCA screening to be cost-effective? Even if every woman with a detected mutation elects to have RRM and RRSO, universal screening still exceeds $1 million per QALY gained. We initially assumed that RRSO reduces ovarian cancer risk by 96%; RRSO alone halves breast cancer risk; RRM alone reduces breast cancer risk by 91%; and both procedures reduce breast cancer risk by 95%.3 Under the optimistic assumption that risk-reducing surgery completely eliminates cancer risk, universal BRCA screening still exceeds $970 000 per QALY gained compared with screening based on family history. If the price of BRCA genetic testing falls below $250 as indicated by Color Genomics, cost-effectiveness dramatically improves to $53 000 per QALY gained, far below the oft-cited $100 000 acceptable cost-effectiveness threshold based on hemodialysis treatment for end-stage renal disease. Given the potential market size of women interested in testing for BRCA and other genes, a drastically lower test price could simultaneously increase test utilization and profitability. Bundling BRCA testing with other cancer-associated genes, such as p53 or PALB2, could further improve cost-effectiveness estimates, although more information is needed about the long-term risks of cancer associated with such rare mutations. The logistics of genetically testing more than 100 million women pose additional challenges and would likely overwhelm the capacity of existing genetic counselors. Asking primary care physicians to counsel and test patients would further tax overburdened clinicians, so other avenues, such as mail-order testing and online counseling, would need to be explored. Before a broad genetic testing program in the United States is realistically considered, understanding the relative value of such a program is important, especially because these resources may offer more health benefits if spent on earlier or more frequent breast imaging. Even though a very small percentage of women would benefit from universal BRCA testing, at $2000 to $4000 per test, such a strategy is an inefficient use of health care resources. Back to top Article Information Corresponding Author: Elisa F. Long, PhD, UCLA Anderson School of Management, 110 Westwood Plaza, Ste B508, Los Angeles, CA 90095 (elisa.long@anderson.ucla.edu). Published Online: September 3, 2015. doi:10.1001/jamaoncol.2015.2340. Conflict of Interest Disclosures: None reported. Additional Contributions: Dr Ganz is currently on the Advisory Board for InformedDNA. References 1. US Breast Cancer Statistics. 2014; http://www.breastcancer.org/symptoms/understand_bc/statistics. Accessed July 13, 2015. 2. King MC, Levy-Lahad E, Lahad A. Population-based screening for BRCA1 and BRCA2: 2014 Lasker Award. JAMA. 2014;312(11):1091-1092.PubMedGoogle ScholarCrossref 3. Manchanda R, Legood R, Burnell M, et al. Cost-effectiveness of population screening for BRCA mutations in Ashkenazi Jewish women compared with family history-based testing. J Natl Cancer Inst. 2015;107(1):380.PubMedGoogle ScholarCrossref 4. Grann VR, Patel PR, Jacobson JS, et al. Comparative effectiveness of screening and prevention strategies among BRCA1/2-affected mutation carriers. Breast Cancer Res Treat. 2011;125(3):837-847.PubMedGoogle ScholarCrossref 5. Plevritis SK, Kurian AW, Sigal BM, et al. Cost-effectiveness of screening BRCA1/2 mutation carriers with breast magnetic resonance imaging. JAMA. 2006;295(20):2374-2384.PubMedGoogle ScholarCrossref 6. Schousboe JT, Kerlikowske K, Loh A, Cummings SR. Personalizing mammography by breast density and other risk factors for breast cancer: analysis of health benefits and cost-effectiveness. Ann Intern Med. 2011;155(1):10-20.PubMedGoogle ScholarCrossref 7. Moore SG, Shenoy PJ, Fanucchi L, Tumeh JW, Flowers CR. Cost-effectiveness of MRI compared to mammography for breast cancer screening in a high risk population. BMC Health Serv Res. 2009;9:9.PubMedGoogle ScholarCrossref

Journal

JAMA OncologyAmerican Medical Association

Published: Dec 1, 2015

Keywords: cost effectiveness,brca1 protein,decision making,brca1 gene,jews,life expectancy,mammography,ovarian neoplasms,quality-adjusted life years,breast cancer,screening,breast neoplasm screening,cancer screening,evidence-based practice,quality-adjusted life expectancy,genetic screening

References