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Breast-ovarian cancer, familial, susceptibility to, 2(BROVCA2)

MedGen UID:
382625
•Concept ID:
C2675520
•
Finding
Synonyms: BRCA2 Hereditary Breast and Ovarian Cancer; Breast-ovarian cancer, familial 2; BROVCA2
 
Gene (location): BRCA2 (13q13.1)
 
Monarch Initiative: MONDO:0012933
OMIM®: 612555

Disease characteristics

Excerpted from the GeneReview: BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer
BRCA1- and BRCA2-associated hereditary breast and ovarian cancer (HBOC) is characterized by an increased risk for female and male breast cancer, ovarian cancer (including fallopian tube and primary peritoneal cancers), and to a lesser extent other cancers such as prostate cancer, pancreatic cancer, and melanoma primarily in individuals with a BRCA2 pathogenic variant. The risk of developing an associated cancer varies depending on whether HBOC is caused by a BRCA1 or BRCA2 pathogenic variant. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Characteristics  |  Genetically Related (Allelic) Disorders  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  Chapter Notes  |  References
Authors:
Nancie Petrucelli  |  Mary B Daly  |  Tuya Pal   view full author information

Clinical features

From HPO
Ovarian neoplasm
MedGen UID:
181539
•Concept ID:
C0919267
•
Neoplastic Process
A tumor (abnormal growth of tissue) of the ovary.
See: Feature record | Search on this feature
Breast carcinoma
MedGen UID:
146260
•Concept ID:
C0678222
•
Neoplastic Process
The presence of a carcinoma of the breast.
See: Feature record | Search on this feature
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Professional guidelines

PubMed

NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2024.
Daly MB, Pal T, Maxwell KN, Churpek J, Kohlmann W, AlHilli Z, Arun B, Buys SS, Cheng H, Domchek SM, Friedman S, Giri V, Goggins M, Hagemann A, Hendrix A, Hutton ML, Karlan BY, Kassem N, Khan S, Khoury K, Kurian AW, Laronga C, Mak JS, Mansour J, McDonnell K, Menendez CS, Merajver SD, Norquist BS, Offit K, Rash D, Reiser G, Senter-Jamieson L, Shannon KM, Visvanathan K, Welborn J, Wick MJ, Wood M, Yurgelun MB, Dwyer MA, Darlow SD
J Natl Compr Canc Netw 2023 Oct;21(10):1000-1010. doi: 10.6004/jnccn.2023.0051. PMID: 37856201
Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.
Daly MB, Pal T, Berry MP, Buys SS, Dickson P, Domchek SM, Elkhanany A, Friedman S, Goggins M, Hutton ML; CGC, Karlan BY, Khan S, Klein C, Kohlmann W; CGC, Kurian AW, Laronga C, Litton JK, Mak JS; LCGC, Menendez CS, Merajver SD, Norquist BS, Offit K, Pederson HJ, Reiser G; CGC, Senter-Jamieson L; CGC, Shannon KM, Shatsky R, Visvanathan K, Weitzel JN, Wick MJ, Wisinski KB, Yurgelun MB, Darlow SD, Dwyer MA
J Natl Compr Canc Netw 2021 Jan 6;19(1):77-102. doi: 10.6004/jnccn.2021.0001. PMID: 33406487
Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: US Preventive Services Task Force Recommendation Statement.
US Preventive Services Task Force, Owens DK, Davidson KW, Krist AH, Barry MJ, Cabana M, Caughey AB, Doubeni CA, Epling JW Jr, Kubik M, Landefeld CS, Mangione CM, Pbert L, Silverstein M, Simon MA, Tseng CW, Wong JB
JAMA 2019 Aug 20;322(7):652-665. doi: 10.1001/jama.2019.10987. PMID: 31429903

Curated

UK NICE Clinical Guideline CG164, Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer, 2023

NCCN Clinical Practice Guidelines in Oncology, Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic version 2.2022

American College of Medical Genetics and Genomics, Genomic Testing (Secondary Findings) ACT Sheet, BRCA1 and BRCA2 Pathogenic Variants (Hereditary Breast and Ovarian Cancer), 2019

Suggested Reading

PubMed

Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA1/2-Related Cancer in Women: A Systematic Review for the U.S. Preventive Services Task Force [Internet]
Nelson HD, Pappas M, Cantor A, Haney E, Holmes R, Stillman L
Rockville (MD): Agency for Healthcare Research and Quality (US); 2019 Aug; PMID: 31479213Books & Documents
Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer: Systematic Review to Update the U.S. Preventive Services Task Force Recommendation [Internet]
Nelson HD, Fu R, Goddard K, Mitchell JP, Okinaka-Hu L, Pappas M, Zakher B
Rockville (MD): Agency for Healthcare Research and Quality (US); 2013 Dec; PMID: 24432435Books & Documents
Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers.
Phillips KA, Milne RL, Rookus MA, Daly MB, Antoniou AC, Peock S, Frost D, Easton DF, Ellis S, Friedlander ML, Buys SS, Andrieu N, Noguès C, Stoppa-Lyonnet D, Bonadona V, Pujol P, McLachlan SA, John EM, Hooning MJ, Seynaeve C, Tollenaar RA, Goldgar DE, Terry MB, Caldes T, Weideman PC, Andrulis IL, Singer CF, Birch K, Simard J, Southey MC, Olsson HL, Jakubowska A, Olah E, Gerdes AM, Foretova L, Hopper JL
J Clin Oncol 2013 Sep 1;31(25):3091-9. Epub 2013 Aug 5 doi: 10.1200/JCO.2012.47.8313. PMID: 23918944Free PMC Article
Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality.
Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, Isaacs C, Garber JE, Neuhausen SL, Matloff E, Eeles R, Pichert G, Van t'veer L, Tung N, Weitzel JN, Couch FJ, Rubinstein WS, Ganz PA, Daly MB, Olopade OI, Tomlinson G, Schildkraut J, Blum JL, Rebbeck TR
JAMA 2010 Sep 1;304(9):967-75. doi: 10.1001/jama.2010.1237. PMID: 20810374Free PMC Article

Recent clinical studies

Etiology

NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2024.
Daly MB, Pal T, Maxwell KN, Churpek J, Kohlmann W, AlHilli Z, Arun B, Buys SS, Cheng H, Domchek SM, Friedman S, Giri V, Goggins M, Hagemann A, Hendrix A, Hutton ML, Karlan BY, Kassem N, Khan S, Khoury K, Kurian AW, Laronga C, Mak JS, Mansour J, McDonnell K, Menendez CS, Merajver SD, Norquist BS, Offit K, Rash D, Reiser G, Senter-Jamieson L, Shannon KM, Visvanathan K, Welborn J, Wick MJ, Wood M, Yurgelun MB, Dwyer MA, Darlow SD
J Natl Compr Canc Netw 2023 Oct;21(10):1000-1010. doi: 10.6004/jnccn.2023.0051. PMID: 37856201
Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.
Daly MB, Pal T, Berry MP, Buys SS, Dickson P, Domchek SM, Elkhanany A, Friedman S, Goggins M, Hutton ML; CGC, Karlan BY, Khan S, Klein C, Kohlmann W; CGC, Kurian AW, Laronga C, Litton JK, Mak JS; LCGC, Menendez CS, Merajver SD, Norquist BS, Offit K, Pederson HJ, Reiser G; CGC, Senter-Jamieson L; CGC, Shannon KM, Shatsky R, Visvanathan K, Weitzel JN, Wick MJ, Wisinski KB, Yurgelun MB, Darlow SD, Dwyer MA
J Natl Compr Canc Netw 2021 Jan 6;19(1):77-102. doi: 10.6004/jnccn.2021.0001. PMID: 33406487
Comparison of BRCA versus non-BRCA germline mutations and associated somatic mutation profiles in patients with unselected breast cancer.
Chen B, Zhang G, Li X, Ren C, Wang Y, Li K, Mok H, Cao L, Wen L, Jia M, Li C, Guo L, Wei G, Lin J, Li Y, Zhang Y, Han-Zhang H, Liu J, Lizaso A, Liao N
Aging (Albany NY) 2020 Feb 24;12(4):3140-3155. doi: 10.18632/aging.102783. PMID: 32091409Free PMC Article
Evaluation of ACMG-Guideline-Based Variant Classification of Cancer Susceptibility and Non-Cancer-Associated Genes in Families Affected by Breast Cancer.
Maxwell KN, Hart SN, Vijai J, Schrader KA, Slavin TP, Thomas T, Wubbenhorst B, Ravichandran V, Moore RM, Hu C, Guidugli L, Wenz B, Domchek SM, Robson ME, Szabo C, Neuhausen SL, Weitzel JN, Offit K, Couch FJ, Nathanson KL
Am J Hum Genet 2016 May 5;98(5):801-817. doi: 10.1016/j.ajhg.2016.02.024. PMID: 27153395Free PMC Article
Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.
Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE
J Clin Oncol 2016 May 1;34(13):1460-8. Epub 2016 Mar 14 doi: 10.1200/JCO.2015.65.0747. PMID: 26976419Free PMC Article

Diagnosis

NCCN Guidelines® Insights: Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2024.
Daly MB, Pal T, Maxwell KN, Churpek J, Kohlmann W, AlHilli Z, Arun B, Buys SS, Cheng H, Domchek SM, Friedman S, Giri V, Goggins M, Hagemann A, Hendrix A, Hutton ML, Karlan BY, Kassem N, Khan S, Khoury K, Kurian AW, Laronga C, Mak JS, Mansour J, McDonnell K, Menendez CS, Merajver SD, Norquist BS, Offit K, Rash D, Reiser G, Senter-Jamieson L, Shannon KM, Visvanathan K, Welborn J, Wick MJ, Wood M, Yurgelun MB, Dwyer MA, Darlow SD
J Natl Compr Canc Netw 2023 Oct;21(10):1000-1010. doi: 10.6004/jnccn.2023.0051. PMID: 37856201
Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.
Daly MB, Pal T, Berry MP, Buys SS, Dickson P, Domchek SM, Elkhanany A, Friedman S, Goggins M, Hutton ML; CGC, Karlan BY, Khan S, Klein C, Kohlmann W; CGC, Kurian AW, Laronga C, Litton JK, Mak JS; LCGC, Menendez CS, Merajver SD, Norquist BS, Offit K, Pederson HJ, Reiser G; CGC, Senter-Jamieson L; CGC, Shannon KM, Shatsky R, Visvanathan K, Weitzel JN, Wick MJ, Wisinski KB, Yurgelun MB, Darlow SD, Dwyer MA
J Natl Compr Canc Netw 2021 Jan 6;19(1):77-102. doi: 10.6004/jnccn.2021.0001. PMID: 33406487
Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings.
Bonache S, Esteban I, Moles-Fernández A, Tenés A, Duran-Lozano L, Montalban G, Bach V, Carrasco E, Gadea N, López-Fernández A, Torres-Esquius S, Mancuso F, Caratú G, Vivancos A, Tuset N, Balmaña J, Gutiérrez-Enríquez S, Diez O
J Cancer Res Clin Oncol 2018 Dec;144(12):2495-2513. Epub 2018 Oct 10 doi: 10.1007/s00432-018-2763-9. PMID: 30306255
Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.
Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE
J Clin Oncol 2016 May 1;34(13):1460-8. Epub 2016 Mar 14 doi: 10.1200/JCO.2015.65.0747. PMID: 26976419Free PMC Article
Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel.
Tung N, Battelli C, Allen B, Kaldate R, Bhatnagar S, Bowles K, Timms K, Garber JE, Herold C, Ellisen L, Krejdovsky J, DeLeonardis K, Sedgwick K, Soltis K, Roa B, Wenstrup RJ, Hartman AR
Cancer 2015 Jan 1;121(1):25-33. Epub 2014 Sep 3 doi: 10.1002/cncr.29010. PMID: 25186627

Therapy

Surgical Management of Hereditary Breast Cancer.
Berger ER, Golshan M
Genes (Basel) 2021 Aug 31;12(9) doi: 10.3390/genes12091371. PMID: 34573353Free PMC Article
Uptake and Predictors of Opportunistic Salpingectomy for Ovarian Cancer Risk Reduction in the United States.
Karia PS, Joshu CE, Visvanathan K
Cancer Prev Res (Phila) 2021 Dec;14(12):1101-1110. Epub 2021 Aug 19 doi: 10.1158/1940-6207.CAPR-21-0121. PMID: 34413116Free PMC Article
Modified panel-based genetic counseling for ovarian cancer susceptibility: A randomized non-inferiority study.
McCuaig JM, Tone AA, Maganti M, Romagnuolo T, Ricker N, Shuldiner J, Rodin G, Stockley T, Kim RH, Bernardini MQ
Gynecol Oncol 2019 Apr;153(1):108-115. Epub 2019 Jan 10 doi: 10.1016/j.ygyno.2018.12.027. PMID: 30638766
BRCA1 allele-specific expression in genetic predisposed breast/ovarian cancer.
Jamard E, Volard B, Dugué AE, Legros A, Leconte A, Clarisse B, Davy G, Polycarpe F, Dugast C, Abadie C, Frebourg T, Tinat J, Tennevet I, Layet V, Joly F, Castéra L, Berthet P, Vaur D, Krieger S
Fam Cancer 2017 Apr;16(2):167-171. doi: 10.1007/s10689-016-9940-2. PMID: 27783335
Association between family cancer history and risk of pancreatic cancer.
Schulte A, Pandeya N, Fawcett J, Fritschi L, Klein K, Risch HA, Webb PM, Whiteman DC, Neale RE
Cancer Epidemiol 2016 Dec;45:145-150. Epub 2016 Oct 31 doi: 10.1016/j.canep.2016.10.005. PMID: 27810486

Prognosis

Mis-splicing in breast cancer: identification of pathogenic BRCA2 variants by systematic minigene assays.
Fraile-Bethencourt E, Valenzuela-Palomo A, Díez-Gómez B, Goina E, Acedo A, Buratti E, Velasco EA
J Pathol 2019 Aug;248(4):409-420. Epub 2019 Apr 23 doi: 10.1002/path.5268. PMID: 30883759
Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings.
Bonache S, Esteban I, Moles-Fernández A, Tenés A, Duran-Lozano L, Montalban G, Bach V, Carrasco E, Gadea N, López-Fernández A, Torres-Esquius S, Mancuso F, Caratú G, Vivancos A, Tuset N, Balmaña J, Gutiérrez-Enríquez S, Diez O
J Cancer Res Clin Oncol 2018 Dec;144(12):2495-2513. Epub 2018 Oct 10 doi: 10.1007/s00432-018-2763-9. PMID: 30306255
Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.
Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE
J Clin Oncol 2016 May 1;34(13):1460-8. Epub 2016 Mar 14 doi: 10.1200/JCO.2015.65.0747. PMID: 26976419Free PMC Article
Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel.
Tung N, Battelli C, Allen B, Kaldate R, Bhatnagar S, Bowles K, Timms K, Garber JE, Herold C, Ellisen L, Krejdovsky J, DeLeonardis K, Sedgwick K, Soltis K, Roa B, Wenstrup RJ, Hartman AR
Cancer 2015 Jan 1;121(1):25-33. Epub 2014 Sep 3 doi: 10.1002/cncr.29010. PMID: 25186627
A high proportion of DNA variants of BRCA1 and BRCA2 is associated with aberrant splicing in breast/ovarian cancer patients.
Sanz DJ, Acedo A, Infante M, Durán M, Pérez-Cabornero L, Esteban-Cardeñosa E, Lastra E, Pagani F, Miner C, Velasco EA
Clin Cancer Res 2010 Mar 15;16(6):1957-67. Epub 2010 Mar 9 doi: 10.1158/1078-0432.CCR-09-2564. PMID: 20215541

Clinical prediction guides

Mis-splicing in breast cancer: identification of pathogenic BRCA2 variants by systematic minigene assays.
Fraile-Bethencourt E, Valenzuela-Palomo A, Díez-Gómez B, Goina E, Acedo A, Buratti E, Velasco EA
J Pathol 2019 Aug;248(4):409-420. Epub 2019 Apr 23 doi: 10.1002/path.5268. PMID: 30883759
Multigene panel testing beyond BRCA1/2 in breast/ovarian cancer Spanish families and clinical actionability of findings.
Bonache S, Esteban I, Moles-Fernández A, Tenés A, Duran-Lozano L, Montalban G, Bach V, Carrasco E, Gadea N, López-Fernández A, Torres-Esquius S, Mancuso F, Caratú G, Vivancos A, Tuset N, Balmaña J, Gutiérrez-Enríquez S, Diez O
J Cancer Res Clin Oncol 2018 Dec;144(12):2495-2513. Epub 2018 Oct 10 doi: 10.1007/s00432-018-2763-9. PMID: 30306255
Frequency of Germline Mutations in 25 Cancer Susceptibility Genes in a Sequential Series of Patients With Breast Cancer.
Tung N, Lin NU, Kidd J, Allen BA, Singh N, Wenstrup RJ, Hartman AR, Winer EP, Garber JE
J Clin Oncol 2016 May 1;34(13):1460-8. Epub 2016 Mar 14 doi: 10.1200/JCO.2015.65.0747. PMID: 26976419Free PMC Article
Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel.
Tung N, Battelli C, Allen B, Kaldate R, Bhatnagar S, Bowles K, Timms K, Garber JE, Herold C, Ellisen L, Krejdovsky J, DeLeonardis K, Sedgwick K, Soltis K, Roa B, Wenstrup RJ, Hartman AR
Cancer 2015 Jan 1;121(1):25-33. Epub 2014 Sep 3 doi: 10.1002/cncr.29010. PMID: 25186627
A high proportion of DNA variants of BRCA1 and BRCA2 is associated with aberrant splicing in breast/ovarian cancer patients.
Sanz DJ, Acedo A, Infante M, Durán M, Pérez-Cabornero L, Esteban-Cardeñosa E, Lastra E, Pagani F, Miner C, Velasco EA
Clin Cancer Res 2010 Mar 15;16(6):1957-67. Epub 2010 Mar 9 doi: 10.1158/1078-0432.CCR-09-2564. PMID: 20215541

Recent systematic reviews

Large-scale meta-analysis of mutations identified in panels of breast/ovarian cancer-related genes - Providing evidence of cancer predisposition genes.
Suszynska M, Klonowska K, Jasinska AJ, Kozlowski P
Gynecol Oncol 2019 May;153(2):452-462. Epub 2019 Feb 4 doi: 10.1016/j.ygyno.2019.01.027. PMID: 30733081
Which BRCA genetic testing programs are ready for implementation in health care? A systematic review of economic evaluations.
D'Andrea E, Marzuillo C, De Vito C, Di Marco M, Pitini E, Vacchio MR, Villari P
Genet Med 2016 Dec;18(12):1171-1180. Epub 2016 Apr 14 doi: 10.1038/gim.2016.29. PMID: 27906166Free PMC Article
A new paradigm of genetic testing for hereditary breast/ovarian cancers.
Kwong A, Chen JW, Shin VY
Hong Kong Med J 2016 Apr;22(2):171-7. Epub 2016 Mar 14 doi: 10.12809/hkmj154634. PMID: 26980575

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • NICE, 2023
      UK NICE Clinical Guideline CG164, Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer, 2023
    • NCCN, 2022
      NCCN Clinical Practice Guidelines in Oncology, Genetic/Familial High-Risk Assessment: Breast, Ovarian, and Pancreatic version 2.2022
    • ACMG ACT, 2019
      American College of Medical Genetics and Genomics, Genomic Testing (Secondary Findings) ACT Sheet, BRCA1 and BRCA2 Pathogenic Variants (Hereditary Breast and Ovarian Cancer), 2019

    Reviews

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