Cancer Risks for BRCA1 and BRCA2 Mutation Carriers: Results From Prospective Analysis of EMBRACE
Abstract
Background Reliable estimates of cancer risk are critical for guiding management of BRCA1 and BRCA2 mutation carriers. The aims of this study were to derive penetrance estimates for breast cancer, ovarian cancer, and contralateral breast cancer in a prospective series of mutation carriers and to assess how these risks are modified by common breast cancer susceptibility alleles. Methods Prospective cancer risks were estimated using a cohort of 978 BRCA1 and 909 BRCA2 carriers from the United Kingdom. Nine hundred eighty-eight women had no breast or ovarian cancer diagnosis at baseline, 1509 women were unaffected by ovarian cancer, and 651 had been diagnosed with unilateral breast cancer. Cumulative risks were obtained using Kaplan-Meier estimates. Associations between cancer risk and covariables of interest were evaluated using Cox regression. All statistical tests were two-sided. Results The average cumulative risks by age 70 years for BRCA1 carriers were estimated to be 60% (95% confidence interval [CI] = 44% to 75%) for breast cancer, 59% (95% CI = 43% to 76%) for ovarian cancer, and 83% (95% CI = 69% to 94%) for contralateral breast cancer. For BRCA2 carriers, the corresponding risks were 55% (95% CI = 41% to 70%) for breast cancer, 16.5% (95% CI = 7.5% to 34%) for ovarian cancer, and 62% (95% CI = 44% to 79.5%) for contralateral breast cancer. BRCA2 carriers in the highest tertile of risk, defined by the joint genotype distribution of seven single nucleotide polymorphisms…
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Carriers of pathogenic BRCA2 variants have a lifetime risk of developing ovarian cancer ranging from 16.5% to 27.0%.
“while the risk of developing ovarian cancer ranges from 16.5% to 27.0% [8, 9]”
From Screening, Risk Reduction Strategies, and Clinical Management of Unaffected Carriers of <i>BRCA1</i> or <i>BRCA2</i> Pathogenic Variants (2026) · cites this paper as [8]
Carriers of pathogenic BRCA2 variants have a lifetime risk of developing breast cancer ranging from 38% to 84%.
“Carriers of pathogenic BRCA2 variants have a lifetime risk of developing breast cancer ranging from 38% to 84%”
From Screening, Risk Reduction Strategies, and Clinical Management of Unaffected Carriers of <i>BRCA1</i> or <i>BRCA2</i> Pathogenic Variants (2026) · cites this paper as [8]
Cites
Nonparametric Estimation from Incomplete Observations
Kaplan, E. L., & Meier, P. (1958) · Journal of the American Statistical Association · doi:10.1080/01621459.1958.10501452 · Cited by 39,158 · see citing works
Antoniou, A., Pharoah, P. D. P., Narod, S., Risch, H. A., Eyfjord, J. E., Hopper, J. L., Loman, N., Olsson, H., Johannsson, O., Borg, Å., et al. (2003) · The American Journal of Human Genetics · doi:10.1086/375033 · Cited by 3,680 · see citing works
Self-citationRisks of cancer in BRCA1-mutation carriers
FORD, D. (1994) · The Lancet · doi:10.1016/s0140-6736(94)91578-4 · Cited by 1,850 · see citing works
Meijers-Heijboer, H., van Geel, B., van Putten, W. L. J., Henzen-Logmans, S. C., Seynaeve, C., Menke-Pluymers, M. B. E., Bartels, C. C. M., Verhoog, L. C., van den Ouweland, A. M. W., Niermeijer, M. F., et al. (2001) · New England Journal of Medicine · doi:10.1056/nejm200107193450301 · Cited by 973 · see citing works
Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status
Haffty, B. G., Harrold, E., Khan, A. J., Pathare, P., Smith, T. E., Turner, B. C., Glazer, P. M., Ward, B., Carter, D., Matloff, E., et al. (2002) · The Lancet · doi:10.1016/s0140-6736(02)08434-9 · Cited by 307 · see citing works
Predictors of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers
Metcalfe, K., Gershman, S., Lynch, H. T., Ghadirian, P., Tung, N., Kim-Sing, C., Olopade, O. I., Domchek, S., McLennan, J., Eisen, A., et al. (2011) · British Journal of Cancer · doi:10.1038/bjc.2011.120 · Cited by 232 · see citing works
Malone, K. E., Begg, C. B., Haile, R. W., Borg, A., Concannon, P., Tellhed, L., Xue, S., Teraoka, S., Bernstein, L., Capanu, M., et al. (2010) · Journal of Clinical Oncology · doi:10.1200/jco.2009.24.2495 · Cited by 191 · see citing works
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Kuchenbaecker, K. B., Hopper, J. L., Barnes, D. R., Phillips, K.-A., Mooij, T. M., Roos-Blom, M.-J., Jervis, S., van Leeuwen, F. E., Milne, R. L., Andrieu, N., et al. (2017) · JAMA · doi:10.1001/jama.2017.7112 · Cited by 2,954 · see citing works
Self-citationGermline Mutations in Predisposition Genes in Pediatric Cancer
Zhang, J., Walsh, M. F., Wu, G., Edmonson, M. N., Gruber, T. A., Easton, J., Hedges, D., Ma, X., Zhou, X., Yergeau, D. A., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1508054 · Cited by 1,345 · see citing works
Pathogenesis of Triple-Negative Breast Cancer
Derakhshan, F., & Reis-Filho, J. S. (2022) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-042420-093238 · Cited by 714 · see citing works
Hereditary breast and ovarian cancer: new genes in confined pathways
Nielsen, F. C., van Overeem Hansen, T., & Sørensen, C. S. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.72 · Cited by 367 · see citing works
Gallagher, S., Hughes, E., Wagner, S., Tshiaba, P., Rosenthal, E., Roa, B. B., Kurian, A. W., Domchek, S. M., Garber, J., Lancaster, J., et al. (2020) · JAMA Network Open · doi:10.1001/jamanetworkopen.2020.8501 · Cited by 137 · see citing works
van den Broek, A. J., van ’t Veer, L. J., Hooning, M. J., Cornelissen, S., Broeks, A., Rutgers, E. J., Smit, V. T. H. B. M., Cornelisse, C. J., van Beek, M., Janssen-Heijnen, M. L., et al. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2015.62.3942 · Cited by 104 · see citing works
High risk of in-breast tumor recurrence after BRCA1/2-associated breast cancer
Nilsson, M. P., Hartman, L., Kristoffersson, U., Johannsson, O. T., Borg, Å., Henriksson, K., Lanke, E., Olsson, H., & Loman, N. (2014) · Breast Cancer Research and Treatment · doi:10.1007/s10549-014-3115-3 · Cited by 56 · see citing works
Cancer mortality in the oldest old: a global overview
Hashim, D., Carioli, G., Malvezzi, M., Bertuccio, P., Waxman, S., Negri, E., La Vecchia, C., & Boffetta, P. (2020) · Aging · doi:10.18632/aging.103503 · Cited by 36 · see citing works
Nero, C., Ciccarone, F., Boldrini, L., Lenkowicz, J., Paris, I., Capoluongo, E. D., Testa, A. C., Fagotti, A., Valentini, V., & Scambia, G. (2020) · Scientific Reports · doi:10.1038/s41598-020-73505-2 · Cited by 31 · see citing works
van den Broek, A. J., de Ruiter, K., van 't Veer, L. J., Tollenaar, R. A. E. M., van Leeuwen, F. E., Verhoef, S., & Schmidt, M. K. (2015) · European Journal of Human Genetics · doi:10.1038/ejhg.2014.161 · Cited by 18 · see citing works
Abdel-Razeq, H., & Mansour, R. (2026) · World Journal of Oncology · doi:10.14740/wjon2692
- Authors
- Mavaddat, N., Peock, S., Frost, D., Ellis, S., Platte, R., Fineberg, E., Evans, D. G., Izatt, L., Eeles, R. A., Adlard, J., Davidson, R., Eccles, D., Cole, T., Cook, J., Brewer, C., Tischkowitz, M., Douglas, F., Hodgson, S., Walker, L., Porteous, M. E., Morrison, P. J., Side, L. E., Kennedy, M. J., Houghton, C., Donaldson, A., Rogers, M. T., Dorkins, H., Miedzybrodzka, Z., Gregory, H., Eason, J., Barwell, J., McCann, E., Murray, A., Antoniou, A. C., Easton, D. F., & EMBRACE, O. B. O.
- ORCID
- Mavaddat, Nasim
- Evans, D. Gareth
- Izatt, Louise
- Eeles, Rosalind A.
- Adlard, Julian
- Eccles, Diana
- Cook, Jackie
- Tischkowitz, Marc
- Hodgson, Shirley
- Morrison, Patrick J.
- Kennedy, M. John
- Donaldson, Alan
- Dorkins, Huw
- Miedzybrodzka, Zosia
- Gregory, Helen
- Eason, Jacqueline
- Barwell, Julian
- Murray, Alex
- Antoniou, Antonis C.
- Easton, Douglas F.
- Venue
- JNCI: Journal of the National Cancer Institute
- Publisher
- Oxford University Press (OUP)
- Published
- 2013-04
- Volume
- 105
- Issue
- 11
- Pages
- 812-822
- ISSN
- 0027-8874 (ISSN-L)
- 1460-2105
- OpenAlex
- W2143924924
- Cited by
- 951
- References
- 7
- Citations by year
- 2026: 33 · 2025: 49 · 2024: 54 · 2023: 47 · 2022: 84 · 2021: 76 · 2020: 86 · 2019: 83 · 2018: 87 · 2017: 121 · 2016: 80 · 2015: 75 · 2014: 52 · 2013: 22
- FWCI
- 50.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JNCI Journal of the National Cancer Institute (publishedVersion)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- UCL Discovery (University College London) (submittedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Cancer Research UK (11174, C1287‐A10118, 15007, 10118, 11022, C1287/A11990)
- National Institute for Health and Care Research (NF-SI-0510-10096)
- Versus Arthritis (C5047/A8385)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
- Health Sciences › Medicine › Epidemiology › Multiple and Secondary Primary Cancers
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- BRCA1 mutation carriers, BRCA2 mutation carriers, cancer risk assessment, breast cancer, ovarian cancer, contralateral breast cancer, penetrance, cumulative risk, single nucleotide polymorphisms
- MeSH terms
- Adult, Aged, Breast Neoplasms, Female, United Kingdom, Heterozygote, Humans, Ireland, Middle Aged, Mutation, Ovarian Neoplasms, Ovariectomy, Primary Prevention, Prospective Studies, Surveys and Questionnaires, Risk Factors, Confounding Factors, Epidemiologic, Incidence, Proportional Hazards Models, Odds Ratio, Risk Assessment, BRCA1 Protein, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, BRCA2 Protein, Kaplan-Meier Estimate, Salpingectomy
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