Examining the uptake of predictive BRCA testing in the UK; findings and implications.
Adult
Age Factors
BRCA1 Protein
/ genetics
BRCA2 Protein
/ genetics
Educational Status
Female
Genetic Carrier Screening
/ statistics & numerical data
Genetic Counseling
/ psychology
Health Knowledge, Attitudes, Practice
Hereditary Breast and Ovarian Cancer Syndrome
/ diagnosis
Humans
Male
United Kingdom
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
04 2021
04 2021
Historique:
received:
04
07
2020
accepted:
29
10
2020
revised:
19
10
2020
pubmed:
18
12
2020
medline:
15
1
2022
entrez:
17
12
2020
Statut:
ppublish
Résumé
Predictive BRCA testing is offered to asymptomatic individuals to predict future risk where a variant has been identified in a relative. It is uncertain whether all eligible relatives access testing, and whether this is related to health care inequalities. Our aim was to analyse trends and inequalities in uptake of testing, and identify predictors of testing and time-to-receipt of testing. A database from April 2010 to March 2017 was collated. Multivariate analysis explored individual associations with testing. Predictor variables included gender, BRCA test type, cancer history, Index of Multiple Deprivation (IMD) and education status. To evaluate factors associated with time-to-testing, a Cox proportional-hazards (CP) model was used. Of 779 tests undertaken, 336 (43.1%) were identified with a BRCA variant. A total of 537 (68.9%) were female and in 83.4% (387/464) of probands, predictive testing was received by relatives. Analysis identified inequalities since decreased testing was found when the proband was unaffected by cancer (OR 0.14, 95% CI 0.06-0.33). Median time-to-testing was 390 days (range, 0-7090 days) and the CP model also identified inequalities in the hazard ratio (HR) for testing for people aged >40 was higher than for aged <40 (HR 1.41, 95% CI 1.20-1.67) and BRCA2 testing was higher than for BRCA1 testing (HR 1.39, 95% CI 1.18-1.64). Reduced testing was found when probands were unaffected by cancer and time-to-testing was found to vary by age and BRCA1/2 test. Given limited study sample size, further research is recommended to examine inequalities in predictive BRCA testing.
Identifiants
pubmed: 33328582
doi: 10.1038/s41431-020-00783-9
pii: 10.1038/s41431-020-00783-9
pmc: PMC8115171
doi:
Substances chimiques
BRCA1 Protein
0
BRCA2 Protein
0
BRCA2 protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
699-708Subventions
Organisme : Medical Research Council
ID : MR/L006758/1
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Références
Chornokur G, Amankwah EK, Schildkraut JM, Phelan CM. Global ovarian cancer health disparities. Gynecol Oncol. 2013;129:258–64. https://doi.org/10.1016/j.ygyno.2012.12.016 .
doi: 10.1016/j.ygyno.2012.12.016
pubmed: 23266352
Rosenthal ET, Evans B, Kidd J, Brown K, Gorringe H, van Orman M, et al. Increased identification of candidates for high-risk breast cancer screening through expanded genetic testing. J Am Coll Radiol. 2017;14:561–8. https://doi.org/10.1016/j.jacr.2016.10.003 .
doi: 10.1016/j.jacr.2016.10.003
pubmed: 28011157
Castro E, Goh C, Olmos D, Saunders E, Leongamornlert D, Tymrakiewicz M, et al. Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer. J Clin Oncol. 2013;31:1748–57. https://doi.org/10.1200/JCO.2012.43.1882 .
doi: 10.1200/JCO.2012.43.1882
pubmed: 23569316
pmcid: 3641696
Cavanagh H, Rogers KMA. The role of BRCA1 and BRCA2 mutations in prostate, pancreatic and stomach cancers. Hered Cancer Clin Pract. 2015;13:1–7. https://doi.org/10.1186/s13053-015-0038-x .
doi: 10.1186/s13053-015-0038-x
Stoppa-Lyonnet D. The biological effects and clinical implications of BRCA mutations: Where do we go from here?. Eur J Hum Genet. 2016;24:S3–9. https://doi.org/10.1038/ejhg.2016.93 .
doi: 10.1038/ejhg.2016.93
pubmed: 27514841
pmcid: 5141575
Hartmann LC, Lindor NM. The role of risk-reducing surgery in hereditary breast and ovarian cancer. N Engl J Med. 2016;374:454–68. https://doi.org/10.1056/NEJMra1503523 .
doi: 10.1056/NEJMra1503523
pubmed: 26840135
Paluch-Shimon S, Cardoso F, Sessa C, Balmana J, Cardoso MJ, Gilbert F, et al. Prevention and screening in BRCA mutation carriers and other breast/ovarian hereditary cancer syndromes: ESMO clinical practice guidelines for cancer prevention and screening. Ann Oncol. 2016;27:v103–10. https://doi.org/10.1093/annonc/mdw327 .
doi: 10.1093/annonc/mdw327
pubmed: 27664246
National Breast Cancer Foundation Inc. Genetic testing for breast cancer. https://www.nationalbreastcancer.org/genetic-testing-for-breast-cancer . [Accessed 10/12/2020].
Yurgelun MB, Hiller E, Garber JE. Population-wide screening for germline BRCA1 and BRCA2 mutations: Too much of a good thing?. J Clin Oncol. 2015;33:3092–5. https://doi.org/10.1200/JCO.2015.60.8596 .
doi: 10.1200/JCO.2015.60.8596
pubmed: 26282646
Mahon SM. Cancer risks for men with BRCA1/2 mutations. Oncol Nurs Forum. 2014;41:99–101. https://doi.org/10.1007/s10689 .
doi: 10.1007/s10689
pubmed: 24368245
Rauscher EA, Dean M. “I’ve just never gotten around to doing it”: men’s approaches to managing BRCA-related cancer risks. Patient Educ Couns. 2018;101:340–5.
doi: 10.1016/j.pec.2017.07.015
NICE. Familial breast cancer: the classification and care of people at risk of familial breast cancer and management of breast cancer and related risks in people with a family history of breast cancer. Clinical Guideline 164. London; 2013. http://guidance.nice.org.uk/CG164 .
Evans JP, Skrzynia C, Burke W. The complexities of predictive genetic testing. BMJ. 2001;322:1052–6. https://doi.org/10.1136/bmj.322.7293.1052 .
doi: 10.1136/bmj.322.7293.1052
pubmed: 11325775
pmcid: 1120190
Gabai-Kapara E, Lahad A, Kaufman B, Friedman E, Segev S, Renbaum P, et al. Population-based screening for breast and ovarian cancer risk due to BRCA1 and BRCA2. Proc Natl Acad Sci USA. 2014;111:14205–10. https://doi.org/10.1073/pnas.1415979111 .
doi: 10.1073/pnas.1415979111
pubmed: 25192939
Sayani A. Inequities in genetic testing for hereditary breast cancer: implications for public health practice. J Community Genet. 2018;1–5. https://doi.org/10.1007/s12687-018-0370-8 .
Holloway SM, Bernhard B, Campbell H, Cetnarskyj R, Lam WWK. Inequality of use of cancer genetics services by members of breast, ovarian and colorectal cancer families in South East Scotland. Fam Cancer. 2008;7:259–64. https://doi.org/10.1007/s10689-008-9184-x .
doi: 10.1007/s10689-008-9184-x
pubmed: 18246448
Cragun D, Bonner D, Kim J, Akbari MR, Narod SA, Gomez-Fuego A, et al. Factors associated with genetic counseling and BRCA testing in a population-based sample of young Black women with breast cancer. Breast Cancer Res Treat. 2015;151:169–76. https://doi.org/10.1007/s10549-015-3374-7 .
doi: 10.1007/s10549-015-3374-7
pubmed: 25868867
pmcid: 4503247
Yusuf RA, Rogith D, Hovick SRA, Peterson SK, Burton-Chase AM, Fellman BM, et al. Attitudes toward molecular testing for personalized cancer therapy. Cancer. 2015;121:243–50. https://doi.org/10.1002/cncr.28966 .
doi: 10.1002/cncr.28966
pubmed: 25209923
Mai PL, Vadaparampil ST, Breen N, McNeel TS, Wideroff L, Graubard BI. Awareness of cancer susceptibility genetic testing: the 2000, 2005, and 2010 national health interview surveys. Am J Prev Med. 2014;46:440–8. https://doi.org/10.1016/j.amepre.2014.01.002 .
doi: 10.1016/j.amepre.2014.01.002
pubmed: 24745633
pmcid: 4042677
Finney Rutten LJ, Gollust SE, Naveed S, Moser RP. Increasing public awareness of direct-to-consumer genetic tests: Health care access, internet use, and population density correlates. J Cancer Epidemiol. 2012;2012:6–10. https://doi.org/10.1155/2012/309109 .
doi: 10.1155/2012/309109
Heck JE, Franco R, Jurkowski JM, Sheinfeld Gorin S. Awareness of genetic testing for cancer among United States hispanics: the role of acculturation. Community Genet. 2008;11:36–42. https://doi.org/10.1159/000111638 .
doi: 10.1159/000111638
pubmed: 18196916
Butrick M, Kelly S, Peshkin BN, Luta G, Nusbaum R, Hooker GW, et al. Uptake of BRCA1/2 genetic testing in a randomized trial of telephone counseling. Genet Med. 2015;17:467–75. https://doi.org/10.1038/gim.2014.125 .
doi: 10.1038/gim.2014.125
pubmed: 25232856
Pagan J, Su D, Li L, Armstrong K, Asch DA. Racial and ethnic disparities in awareness of genetic testing for cancer risk. Am J Prev Med. 2009;37:524–30. https://doi.org/10.1016/j.amepre.2009.07.021 .
doi: 10.1016/j.amepre.2009.07.021
pubmed: 19944919
Molster C, Charles T, Samanek A, O’Leary P. Australian study on public knowledge of human genetics and health. Public Health Genom. 2009;12:84–91. https://doi.org/10.1159/000164684 .
doi: 10.1159/000164684
Haga SB, O’Daniel JM, Tindall GM, Lipkus IR, Agans R. Survey of U.S. public attitudes towards pharmacogenetic testing. Pharmacogenomics J. 2012;12:197–204. https://doi.org/10.1530/ERC-14-0411 .
doi: 10.1530/ERC-14-0411
pubmed: 21321582
Whitehead M. The concepts and principles of equity and health. Health Promot Int. 1991;6:217–28. https://doi.org/10.1093/heapro/6.3.217 .
doi: 10.1093/heapro/6.3.217
Department for Communities and Local Government. The english index of multiple deprivation (IMD) 2015—guidance. 2015. https://www.gov.uk/government/statistics/english-indices-ofdeprivation-2015 . Accessed 2 May 2020.
Klein J, Moeschberger M. Survival analysis: techniques for censored and truncated data. 2nd ed. New York: Springer; 2003.
Hess KR. Graphical methods for assessing violations of the proportional hazards assumption in cox regression. Stat Med. 1995;14:1707–23. https://doi.org/10.1002/sim.4780141510 .
doi: 10.1002/sim.4780141510
pubmed: 7481205
Sterne JAC, White IR, Carlin JB, Spratt M, Royston P, Kenward MG, et al. Multiple imputation for missing data in epidemiological and clinical research: potential and pitfalls. BMJ. 2009;338:b2393. https://doi.org/10.1136/bmj.b2393 .
doi: 10.1136/bmj.b2393
pubmed: 19564179
pmcid: 2714692
D’Andrea E, Marzuillo C, De Vito C, Di Marco M, Pitini E, Vacchio MR, et al. Which BRCA genetic testing programs are ready for implementation in health care? A systematic review of economic evaluations. Genet Med. 2016;18:1171–80. https://doi.org/10.1038/gim.2016.29 .
doi: 10.1038/gim.2016.29
pubmed: 27906166
pmcid: 5159446
Singh K, Lester J, Karlan B, Bresee C, Geva T, Gordon O. Impact of family history on choosing risk-reducing surgery among BRCA mutation carriers. Am J Obstet Gynecol. 2013;208:329.e1–6. https://doi.org/10.1016/j.ajog.2013.01.026 .
doi: 10.1016/j.ajog.2013.01.026
Metcalfe K, Eisen A, Senter L, Risch HA, Rosen B, Murphy J, et al. International trends in the uptake of cancer risk reduction strategies in women with a BRCA1 or BRCA2 mutation. Br J Cancer. 2019;121:15–21. https://doi.org/10.1038/s41416-019-0446-1 .
doi: 10.1038/s41416-019-0446-1
pubmed: 30971774
pmcid: 6738089
MacLeod R, Beach A, Henriques S, Knopp J, Nelson K, Kerzin-Storrar L. Experiences of predictive testing in young people at risk of Huntington’s disease, familial cardiomyopathy or hereditary breast and ovarian cancer. Eur J Hum Genet. 2013;22:396. https://doi.org/10.1038/ejhg.2013.143 .
doi: 10.1038/ejhg.2013.143
pubmed: 23860040
pmcid: 3925271
Brunstrom K, Murray A, McAllister M. Experiences of women who underwent predictive BRCA 1/2 mutation testing before the age of 30. J Genet Couns. 2016;25:90–100. https://doi.org/10.1007/s10897-015-9845-5 .
doi: 10.1007/s10897-015-9845-5
pubmed: 25983051
Healey E, Taylor N, Greening S, Wakefield CE, Warwick L, Williams R, et al. Quantifying family dissemination and identifying barriers to communication of risk information in Australian BRCA families. Genet Med. 2017;19:1323–31. https://doi.org/10.1038/gim.2017.52 .
doi: 10.1038/gim.2017.52
pubmed: 28492536
Fehniger J, Lin F, Beattie MS, Joseph G, Kaplan C. Family communication of BRCA1/2 results and family uptake of BRCA1/2 testing in a diverse population of BRCA1/2 carriers. J Genet Couns. 2013;22:603–12. https://doi.org/10.1007/s10897-013-9592-4 .
doi: 10.1007/s10897-013-9592-4
pubmed: 23666114
Cheung EL, Olson AD, Yu TM, Han PZ, Beattie MS. Communication of BRCA results and family testing in 1,103 high-risk women. Cancer Epidemiol Biomark Prev. 2010;19:2211–9. https://doi.org/10.1158/1055-9965.EPI-10-0325 .
doi: 10.1158/1055-9965.EPI-10-0325
Lieberman S, Lahad A, Tomer A, Koka S, BenUziyahu M, Raz A, et al. Familial communication and cascade testing among relatives of BRCA population screening participants. Genet Med. 2018;20:1446–54. https://doi.org/10.1038/gim.2018.26 .
doi: 10.1038/gim.2018.26
pubmed: 29595811
Menko FH, ter Stege JA, van der Kolk LE, Jeanson KN, Schats W, Moha DA, et al. The uptake of presymptomatic genetic testing in hereditary breast-ovarian cancer and Lynch syndrome: a systematic review of the literature and implications for clinical practice. Fam Cancer. 2019;18:127–35. https://doi.org/10.1007/s10689-018-0089-z .
doi: 10.1007/s10689-018-0089-z
pubmed: 29846880
Sermijn E, Delesie L, Deschepper E, Pauwels I, Bonduelle M, Teugels E, et al. The impact of an interventional counselling procedure in families with a BRCA1/2 gene mutation: efficacy and safety. Fam Cancer. 2016;15:155–62. https://doi.org/10.1007/s10689-015-9854-4 .
doi: 10.1007/s10689-015-9854-4
pubmed: 26748927
pmcid: 4803813
Black L, McClellan KA, Avard D, Knoppers BM. Intrafamilial disclosure of risk for hereditary breast and ovarian cancer: points to consider. J Community Genet. 2013;4:203–14. https://doi.org/10.1007/s12687-012-0132-y .
doi: 10.1007/s12687-012-0132-y
pubmed: 23275181
George R, Kovak K, Cox SL. Aligning policy to promote cascade genetic screening for prevention and early diagnosis of heritable diseases. J Genet Couns. 2015;24:388–99. https://doi.org/10.1007/s10897-014-9805-5 .
doi: 10.1007/s10897-014-9805-5
pubmed: 25577298
Mitchell C, Goodwin D, Ploem C, Bell J, Hennekam R, Wallace S, et al. Exploring the potential duty of care in clinical genomics under UK law. Med Law Int. 2017;17:158–82. https://doi.org/10.1177/0968533217721966 .
doi: 10.1177/0968533217721966
pubmed: 28943725
pmcid: 5598871
Rothstein MA. Reconsidering the duty to warn genetically at-risk relatives. Genet Med. 2018;20:285–90. https://doi.org/10.1038/gim.2017.257 .
doi: 10.1038/gim.2017.257
pubmed: 29388945
Dheensa S, Lucassen A, Fenwick A. Limitations and pitfalls of using family letters to communicate genetic risk: a qualitative study with patients and healthcare professionals. J Genet Couns. 2018;27:689–701. https://doi.org/10.1007/s10897-017-0164-x .
doi: 10.1007/s10897-017-0164-x
pubmed: 29094272
King M-C, Lahad A, Levy-Lahad E. Proposed shift in screening for breast cancer-reply. JAMA. 2015;313:525–6. https://doi.org/10.1001/jama.2014.17442 .
doi: 10.1001/jama.2014.17442
pubmed: 25647216
King M-C, Levy-Lahad E, Lahad A. Population-based screening for BRCA1 and BRCA2: 2014 Lasker Award. JAMA. 2014;312:1091–2. https://doi.org/10.1001/jama.2014.12483 .
doi: 10.1001/jama.2014.12483
pubmed: 25198398