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Familial cancer of breast

MedGen UID:
87542
•Concept ID:
C0346153
•
Neoplastic Process
Synonym: Breast cancer, familial
SNOMED CT: Familial cancer of breast (254843006)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
•Concept ID:
C0443147
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Multifactorial inheritance
MedGen UID:
109109
•Concept ID:
C0600599
•
Genetic Function
Source: Orphanet
A mode of inheritance that depends on a mixture of major and minor genetic determinants possibly together with environmental factors. Diseases inherited in this manner are termed complex diseases.
Autosomal dominant inheritance (Orphanet)
Multifactorial inheritance (Orphanet)
 
Genes (locations): AKT1 (14q32.33); ATM (11q22.3); BARD1 (2q35); BRCA1 (17q21.31); BRCA2 (13q13.1); BRIP1 (17q23.2); CASP8 (2q33.1); CDH1 (16q22.1); CHEK2 (22q12.1); ESR1 (6q25.1-25.2); HMMR (5q34); KRAS (12p12.1); NQO2 (6p25.2); PALB2 (16p12.2); PHB1 (17q21.33); PIK3CA (3q26.32); PPM1D (17q23.2); RAD51 (15q15.1); RAD54L (1p34.1); RB1CC1 (8q11.23); SLC22A18 (11p15.4); TP53 (17p13.1); XRCC3 (14q32.33)
Related genes: STK11, RAD51D, RAD51C, PTEN
 
Monarch Initiative: MONDO:0016419
OMIM®: 114480
Orphanet: ORPHA227535

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

Additional description

From OMIM
Breast cancer (referring to mammary carcinoma, not mammary sarcoma) is histopathologically and almost certainly etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement.  http://www.omim.org/entry/114480

Clinical features

From HPO
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

Term Hierarchy

Professional guidelines

PubMed

Improving primary care identification of familial breast cancer risk using proactive invitation and decision support.
Qureshi N, Dutton B, Weng S, Sheehan C, Chorley W, Robertson JFR, Kendrick D, Kai J
Fam Cancer 2021 Jan;20(1):13-21. Epub 2020 Jun 11 doi: 10.1007/s10689-020-00188-z. PMID: 32524330Free PMC Article
Identification and management of familial breast cancer in Austria.
Singer CF, Tan YY, Rappaport C
Horm Mol Biol Clin Investig 2017 Nov 30;32(2) doi: 10.1515/hmbci-2017-0025. PMID: 29190211
Cancer genetic risk assessment for individuals at risk of familial breast cancer.
Hilgart JS, Coles B, Iredale R
Cochrane Database Syst Rev 2012 Feb 15;2012(2):CD003721. doi: 10.1002/14651858.CD003721.pub3. PMID: 22336791Free PMC Article

Curated

Breast Cancer, NCCN Guidelines Version 4.2022

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
Cancer Genetics Risk Assessment and Counseling (PDQ®): Health Professional Version.
PDQ Cancer Genetics Editorial Board; PDQ Cancer Genetics Editorial Board
2002 PMID: 26389258
Genetics of Breast and Gynecologic Cancers (PDQ®): Health Professional Version.
PDQ Cancer Genetics Editorial Board
2002 PMID: 26389210

Recent clinical studies

Etiology

Polygenic risk in familial breast cancer: Changing the dynamics of communicating genetic risk.
Gregory G, Das Gupta K, Meiser B, Barlow-Stewart K, Geelan-Small P, Kaur R, Scheepers-Joynt M, McInerny S, Taylor S, Antill Y, Salmon L, Smyth C, Young MA, James PA, Yanes T
J Genet Couns 2022 Feb;31(1):120-129. Epub 2021 Jul 5 doi: 10.1002/jgc4.1458. PMID: 34223688
Evidence for familial clustering in breast cancer age of onset.
Von Holle A, O'Brien KM, Sandler DP, Weinberg CR
Int J Epidemiol 2021 Mar 3;50(1):97-104. doi: 10.1093/ije/dyaa201. PMID: 33247915Free PMC Article
Contrast-enhanced MRI for breast cancer screening.
Mann RM, Kuhl CK, Moy L
J Magn Reson Imaging 2019 Aug;50(2):377-390. Epub 2019 Jan 18 doi: 10.1002/jmri.26654. PMID: 30659696Free PMC Article
RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA-mutated breast cancer.
Cruz C, Castroviejo-Bermejo M, Gutiérrez-Enríquez S, Llop-Guevara A, Ibrahim YH, Gris-Oliver A, Bonache S, Morancho B, Bruna A, Rueda OM, Lai Z, Polanska UM, Jones GN, Kristel P, de Bustos L, Guzman M, Rodríguez O, Grueso J, Montalban G, Caratú G, Mancuso F, Fasani R, Jiménez J, Howat WJ, Dougherty B, Vivancos A, Nuciforo P, Serres-Créixams X, Rubio IT, Oaknin A, Cadogan E, Barrett JC, Caldas C, Baselga J, Saura C, Cortés J, Arribas J, Jonkers J, Díez O, O'Connor MJ, Balmaña J, Serra V
Ann Oncol 2018 May 1;29(5):1203-1210. doi: 10.1093/annonc/mdy099. PMID: 29635390Free PMC Article
Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement.
Siu AL; U.S. Preventive Services Task Force
Ann Intern Med 2016 Feb 16;164(4):279-96. Epub 2016 Jan 12 doi: 10.7326/M15-2886. PMID: 26757170

Diagnosis

Contrast-enhanced MRI for breast cancer screening.
Mann RM, Kuhl CK, Moy L
J Magn Reson Imaging 2019 Aug;50(2):377-390. Epub 2019 Jan 18 doi: 10.1002/jmri.26654. PMID: 30659696Free PMC Article
Skin diseases of the breast and nipple: Benign and malignant tumors.
Waldman RA, Finch J, Grant-Kels JM, Stevenson C, Whitaker-Worth D
J Am Acad Dermatol 2019 Jun;80(6):1467-1481. Epub 2018 Nov 16 doi: 10.1016/j.jaad.2018.08.066. PMID: 30452954
Breast cancer in adolescents and young adults.
Johnson RH, Anders CK, Litton JK, Ruddy KJ, Bleyer A
Pediatr Blood Cancer 2018 Dec;65(12):e27397. Epub 2018 Aug 28 doi: 10.1002/pbc.27397. PMID: 30156052Free PMC Article
Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement.
Siu AL; U.S. Preventive Services Task Force
Ann Intern Med 2016 Feb 16;164(4):279-96. Epub 2016 Jan 12 doi: 10.7326/M15-2886. PMID: 26757170
Familial Risk and Heritability of Cancer Among Twins in Nordic Countries.
Mucci LA, Hjelmborg JB, Harris JR, Czene K, Havelick DJ, Scheike T, Graff RE, Holst K, Möller S, Unger RH, McIntosh C, Nuttall E, Brandt I, Penney KL, Hartman M, Kraft P, Parmigiani G, Christensen K, Koskenvuo M, Holm NV, Heikkilä K, Pukkala E, Skytthe A, Adami HO, Kaprio J; Nordic Twin Study of Cancer (NorTwinCan) Collaboration
JAMA 2016 Jan 5;315(1):68-76. doi: 10.1001/jama.2015.17703. PMID: 26746459Free PMC Article

Therapy

Overall survival in the OlympiA phase III trial of adjuvant olaparib in patients with germline pathogenic variants in BRCA1/2 and high-risk, early breast cancer.
Geyer CE Jr, Garber JE, Gelber RD, Yothers G, Taboada M, Ross L, Rastogi P, Cui K, Arahmani A, Aktan G, Armstrong AC, Arnedos M, Balmaña J, Bergh J, Bliss J, Delaloge S, Domchek SM, Eisen A, Elsafy F, Fein LE, Fielding A, Ford JM, Friedman S, Gelmon KA, Gianni L, Gnant M, Hollingsworth SJ, Im SA, Jager A, Jóhannsson ÓÞ, Lakhani SR, Janni W, Linderholm B, Liu TW, Loman N, Korde L, Loibl S, Lucas PC, Marmé F, Martinez de Dueñas E, McConnell R, Phillips KA, Piccart M, Rossi G, Schmutzler R, Senkus E, Shao Z, Sharma P, Singer CF, Španić T, Stickeler E, Toi M, Traina TA, Viale G, Zoppoli G, Park YH, Yerushalmi R, Yang H, Pang D, Jung KH, Mailliez A, Fan Z, Tennevet I, Zhang J, Nagy T, Sonke GS, Sun Q, Parton M, Colleoni MA, Schmidt M, Brufsky AM, Razaq W, Kaufman B, Cameron D, Campbell C, Tutt ANJ; OlympiA Clinical Trial Steering Committee and Investigators
Ann Oncol 2022 Dec;33(12):1250-1268. Epub 2022 Oct 10 doi: 10.1016/j.annonc.2022.09.159. PMID: 36228963
Celecoxib in Cancer Therapy and Prevention - Review.
Tołoczko-Iwaniuk N, Dziemiańczyk-Pakieła D, Nowaszewska BK, Celińska-Janowicz K, Miltyk W
Curr Drug Targets 2019;20(3):302-315. doi: 10.2174/1389450119666180803121737. PMID: 30073924
Breast cancer screening in young women.
Desreux JAC
Eur J Obstet Gynecol Reprod Biol 2018 Nov;230:208-211. Epub 2018 May 24 doi: 10.1016/j.ejogrb.2018.05.018. PMID: 29804884
Management of hereditary breast and ovarian cancer.
Yamauchi H, Takei J
Int J Clin Oncol 2018 Feb;23(1):45-51. Epub 2017 Nov 28 doi: 10.1007/s10147-017-1208-9. PMID: 29185095
BRCA1 as target for breast cancer prevention and therapy.
Romagnolo AP, Romagnolo DF, Selmin OI
Anticancer Agents Med Chem 2015;15(1):4-14. doi: 10.2174/1871520614666141020153543. PMID: 25329591

Prognosis

Contrast-enhanced MRI for breast cancer screening.
Mann RM, Kuhl CK, Moy L
J Magn Reson Imaging 2019 Aug;50(2):377-390. Epub 2019 Jan 18 doi: 10.1002/jmri.26654. PMID: 30659696Free PMC Article
Skin diseases of the breast and nipple: Benign and malignant tumors.
Waldman RA, Finch J, Grant-Kels JM, Stevenson C, Whitaker-Worth D
J Am Acad Dermatol 2019 Jun;80(6):1467-1481. Epub 2018 Nov 16 doi: 10.1016/j.jaad.2018.08.066. PMID: 30452954
Family history and risk of breast cancer: an analysis accounting for family structure.
Brewer HR, Jones ME, Schoemaker MJ, Ashworth A, Swerdlow AJ
Breast Cancer Res Treat 2017 Aug;165(1):193-200. Epub 2017 Jun 3 doi: 10.1007/s10549-017-4325-2. PMID: 28578505Free PMC Article
Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement.
Siu AL; U.S. Preventive Services Task Force
Ann Intern Med 2016 Feb 16;164(4):279-96. Epub 2016 Jan 12 doi: 10.7326/M15-2886. PMID: 26757170
Familial Risk and Heritability of Cancer Among Twins in Nordic Countries.
Mucci LA, Hjelmborg JB, Harris JR, Czene K, Havelick DJ, Scheike T, Graff RE, Holst K, Möller S, Unger RH, McIntosh C, Nuttall E, Brandt I, Penney KL, Hartman M, Kraft P, Parmigiani G, Christensen K, Koskenvuo M, Holm NV, Heikkilä K, Pukkala E, Skytthe A, Adami HO, Kaprio J; Nordic Twin Study of Cancer (NorTwinCan) Collaboration
JAMA 2016 Jan 5;315(1):68-76. doi: 10.1001/jama.2015.17703. PMID: 26746459Free PMC Article

Clinical prediction guides

Contrast-enhanced MRI for breast cancer screening.
Mann RM, Kuhl CK, Moy L
J Magn Reson Imaging 2019 Aug;50(2):377-390. Epub 2019 Jan 18 doi: 10.1002/jmri.26654. PMID: 30659696Free PMC Article
RAD51 foci as a functional biomarker of homologous recombination repair and PARP inhibitor resistance in germline BRCA-mutated breast cancer.
Cruz C, Castroviejo-Bermejo M, Gutiérrez-Enríquez S, Llop-Guevara A, Ibrahim YH, Gris-Oliver A, Bonache S, Morancho B, Bruna A, Rueda OM, Lai Z, Polanska UM, Jones GN, Kristel P, de Bustos L, Guzman M, Rodríguez O, Grueso J, Montalban G, Caratú G, Mancuso F, Fasani R, Jiménez J, Howat WJ, Dougherty B, Vivancos A, Nuciforo P, Serres-Créixams X, Rubio IT, Oaknin A, Cadogan E, Barrett JC, Caldas C, Baselga J, Saura C, Cortés J, Arribas J, Jonkers J, Díez O, O'Connor MJ, Balmaña J, Serra V
Ann Oncol 2018 May 1;29(5):1203-1210. doi: 10.1093/annonc/mdy099. PMID: 29635390Free PMC Article
Family history and risk of breast cancer: an analysis accounting for family structure.
Brewer HR, Jones ME, Schoemaker MJ, Ashworth A, Swerdlow AJ
Breast Cancer Res Treat 2017 Aug;165(1):193-200. Epub 2017 Jun 3 doi: 10.1007/s10549-017-4325-2. PMID: 28578505Free PMC Article
Familial Risk and Heritability of Cancer Among Twins in Nordic Countries.
Mucci LA, Hjelmborg JB, Harris JR, Czene K, Havelick DJ, Scheike T, Graff RE, Holst K, Möller S, Unger RH, McIntosh C, Nuttall E, Brandt I, Penney KL, Hartman M, Kraft P, Parmigiani G, Christensen K, Koskenvuo M, Holm NV, Heikkilä K, Pukkala E, Skytthe A, Adami HO, Kaprio J; Nordic Twin Study of Cancer (NorTwinCan) Collaboration
JAMA 2016 Jan 5;315(1):68-76. doi: 10.1001/jama.2015.17703. PMID: 26746459Free PMC Article
Hereditary Diffuse Gastric Cancer Syndrome: CDH1 Mutations and Beyond.
Hansford S, Kaurah P, Li-Chang H, Woo M, Senz J, Pinheiro H, Schrader KA, Schaeffer DF, Shumansky K, Zogopoulos G, Santos TA, Claro I, Carvalho J, Nielsen C, Padilla S, Lum A, Talhouk A, Baker-Lange K, Richardson S, Lewis I, Lindor NM, Pennell E, MacMillan A, Fernandez B, Keller G, Lynch H, Shah SP, Guilford P, Gallinger S, Corso G, Roviello F, Caldas C, Oliveira C, Pharoah PD, Huntsman DG
JAMA Oncol 2015 Apr;1(1):23-32. doi: 10.1001/jamaoncol.2014.168. PMID: 26182300

Recent systematic reviews

Cost-Effectiveness of Targeted Genetic Testing for Breast and Ovarian Cancer: A Systematic Review.
Koldehoff A, Danner M, Civello D, Rhiem K, Stock S, Müller D
Value Health 2021 Feb;24(2):303-312. Epub 2021 Jan 5 doi: 10.1016/j.jval.2020.09.016. PMID: 33518037
Levonorgestrel-releasing intrauterine system and breast cancer risk: A systematic review and meta-analysis.
Conz L, Mota BS, Bahamondes L, Teixeira Dória M, Françoise Mauricette Derchain S, Rieira R, Sarian LO
Acta Obstet Gynecol Scand 2020 Aug;99(8):970-982. Epub 2020 Feb 12 doi: 10.1111/aogs.13817. PMID: 31990981
Effect of BRCA2 mutation on familial breast cancer survival: A systematic review and meta-analysis.
Shao J, Yang J, Wang JN, Qiao L, Fan W, Gao QL, Feng YJ
J Huazhong Univ Sci Technolog Med Sci 2015 Oct;35(5):629-634. Epub 2015 Oct 22 doi: 10.1007/s11596-015-1481-7. PMID: 26489613
Family history and risk of endometrial cancer: a systematic review and meta-analysis.
Win AK, Reece JC, Ryan S
Obstet Gynecol 2015 Jan;125(1):89-98. doi: 10.1097/AOG.0000000000000563. PMID: 25560109
Peutz-Jeghers syndrome: a systematic review and recommendations for management.
Beggs AD, Latchford AR, Vasen HF, Moslein G, Alonso A, Aretz S, Bertario L, Blanco I, Bülow S, Burn J, Capella G, Colas C, Friedl W, Møller P, Hes FJ, Järvinen H, Mecklin JP, Nagengast FM, Parc Y, Phillips RK, Hyer W, Ponz de Leon M, Renkonen-Sinisalo L, Sampson JR, Stormorken A, Tejpar S, Thomas HJ, Wijnen JT, Clark SK, Hodgson SV
Gut 2010 Jul;59(7):975-86. doi: 10.1136/gut.2009.198499. PMID: 20581245

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

    • NCCN, 2022
      Breast Cancer, NCCN Guidelines Version 4.2022
    • 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

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    Reviews

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