Skip to main content
SpringerLink
Log in

Das familiäre Mammakarzinom

Familial breast cancer

  • CME Weiterbildung · Zertifizierte Fortbildung
  • Published:
Der Gynäkologe Aims and scope

Zusammenfassung

Mammakarzinome sind überwiegend sporadischen Ursprungs, während 5–10% erblich bedingt sind. Von diesen sind etwa 50% mit Mutationen in den Brustkrebsgenen BRCA1 und BRCA2 assoziiert. BRCA-Mutationsträgerinnen tragen ein lebenslanges Erkrankungsrisiko von 60–80% für Brustkrebs und von 20–40% für Eierstockkrebs. Molekulargenetische Analysen ermöglichen die Identifikation der Frauen mit einem erhöhten Erkrankungsrisiko. Für diese wurde 1996 das deutschlandweite Verbundprojekt „Familiärer Brust- und Eierstockkrebs“ etabliert, das ein interdisziplinäres Beratungs- und Betreuungskonzept entwickelt hat. Neben genetischer Beratung und Testung werden präventive und therapeutische Maßnahmen wie intensivierte Früherkennung, prophylaktische Operationen und neue, maßgeschneiderte Therapieverfahren angeboten.

Abstract

The majority of breast carcinomas occur sporadically, while about 5–10% are of familial origin. These are associated with mutations in the breast cancer genes BRCA1 and BRCA2. Mutation carriers have a life-time risk of 60–80% for breast cancer and 20–40% for ovarian cancer. Molecular genetic analysis allows identifying women with higher risk. Since 1996 the German consortium “Hereditary Breast and Ovarian Cancer” has provided an interdisciplinary approach to genetic counseling and testing. It also offers preventive and therapeutic strategies such as intensified surveillance, prophylactic surgery, and new tailored therapeutic techniques.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Literatur

  1. Miki Y, Swensen J, Shattuck-Eidens D et al (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266:66–71

    Article  CAS  PubMed  Google Scholar 

  2. Wooster R, Bignell G, Lancaster J et al (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature 378:789–792

    Article  CAS  PubMed  Google Scholar 

  3. Chen J, Silver DP, Cantor SB et al (1999) BRCA1, BRCA2 and RAD51 operate I a common DNA damage response pathway. Cancer Res 59:1752–1756

    Google Scholar 

  4. Xia F, Taghian DG, DeFrank JS et al (2001) Deficiency of human BRCA2 leads to impaired homologous recombination but maintains normal nonhomologous end joining. Proc Natl Acad Sci 98:8644–8649

    Article  CAS  PubMed  Google Scholar 

  5. Goldgar DE, Easton DF, Deffenbaugh AM et al (2004) Breast Cancer Information Core (BIC) Steering Committee. Integrated evaluation of DNA sequence variants of unknown clinical significance: application to BRCA1 and BRCA2. Am J Hum Genet 75:535–544

    Article  CAS  PubMed  Google Scholar 

  6. Smith P, McGuffog L, Easton DF et al (2006) A genome wide linkage search for breast cancer susceptibility genes. Genes Chromosomes Cancer 45:646–655

    Article  CAS  PubMed  Google Scholar 

  7. Easton DF, Pooley KA, Dunning AM et al (2007) Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447:1087–1093

    Article  CAS  PubMed  Google Scholar 

  8. Meijers-Hejboer H, Ouweland A van den, Klijn J et al (2002) Low penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 and BRCA2 mutations. Nat Genet 31:55–59

    Article  CAS  Google Scholar 

  9. Teraoka SN, Malone KE, Doody DR et al (2001) Increased frequency of ATM mutations in breast carcinoma patients with early onset disease and ovarian cancer. Cancer 93:479–487

    Article  Google Scholar 

  10. Albrecht U (2008) Stufe-3-Leitlinie Früherkennung, Diagnostik und Therapie des Mammakarzinoms

  11. Turner NC, Reis-Filho JS (2006) Basal-like breast cancer and the BRCA1 phenotype. Oncogene 25:5846–5853

    Article  CAS  PubMed  Google Scholar 

  12. Honrado E, Benitez J, Palacios J (2005) The molecular pathology of hereditary breast cancer: Genetic testing and therapeutic implications. Mod Pathol 18:1305–1320

    Article  CAS  PubMed  Google Scholar 

  13. Foulkes WD, Stefansson IM, Chappuis PO et al (2003) Germline BRCA1 mutations an a basal epithelial phenotype in breast cancer. J Natl Cancer Inst 95:1482–1485

    CAS  PubMed  Google Scholar 

  14. Turner NC, Reis-Filho JS, Russel AM et al (2007) BRCA1 dysfunction in sporadic basallike breast cancer. Oncogene 26:2126–2132

    Article  CAS  PubMed  Google Scholar 

  15. Bane AL, Beck JC, Bleiweiss I et al (2007) BRCA2 mutation-associated breast cancers exhibit a distinguishing phenotype based on morphology and molecular profiles from tissue microarrays. Am J Surg Pathol 31:121–128

    Article  PubMed  Google Scholar 

  16. Farshid G, Balleine RL, Cummings M et al (2006) Morphology of breast cancer as means of triage of patients for BRCA1 genetic testing. Am J Surg Pathol 30:1357–1366

    Article  PubMed  Google Scholar 

  17. Lakhani SR, Reis-Filho JS, Fulford L et al (2005) Prediction of BRCA1 status in patients with breast cancer using estrogen receptor and basal phenotype. Clin Cancer Res 11:5175–5178

    Article  CAS  PubMed  Google Scholar 

  18. Gesellschaft der epidemiologischen Krebsregister in Deutschland e.V. und das Robert-Koch-Institut (2006) Krebs in Deutschland, 5. überarbeitete, aktualisierte Ausgabe. Saarbrücken

  19. Tilanus-Linthorst MM, Kriege M, Boetes C et al (2005) Hereditary breast cancer growth rates and ist impact on screening policy. Eur J Cancer 41:1610–1617

    Article  PubMed  Google Scholar 

  20. Rhiem K, Flucke U, Schmutzler RK (2006) BRCA1-associated breast carcinomas frequently present with benign sonographic features. AJR 186:E11–E12

    Article  PubMed  Google Scholar 

  21. Metcalfe K, Lynch HT, Ghadirian P et al (2004) Contralateral breast cancer in BRCA1 and BRCA2 mutations carriers. J Clin Oncol 22:2328–2335

    Article  CAS  PubMed  Google Scholar 

  22. Verhoog LC, Brekelmans CT, Seynaeve C et al (2000) Contralateral breast cancer risk is influenced by the age at onset in BRCA1-associated breast cancer. Br J Cancer 83:384–386

    Article  CAS  PubMed  Google Scholar 

  23. Meijers-Heijboer H, Geel B van, Putten WL van et al (2001) Breast cancer after prophylactic bilateral mastectomy in women with BRCA1 and BRCA2 mutation. N Engl J Med 345:159–164

    Article  CAS  PubMed  Google Scholar 

  24. Rebbeck TR, Friebel T, Lynch HT (2004) bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers. The PROSE Study Group. J Clin Oncol 22:1055–1062

    Article  PubMed  Google Scholar 

  25. Kauff ND, Satagopan JM, Robson ME et al (2002) Risk reducing salpingo-oophorectomy in women with BRCA1 and BRCA2 mutation. N Engl J Med 346:1609–1615

    Article  PubMed  Google Scholar 

  26. Bosse K, Rhiem K, Wappenschmidt B et al (2006) Screening for ovarian cancer by transvaginal ultrasound and serum CA125 measurement in women with familial predisposition; a prospective cohort study. Gynecol Oncol 1033:1077–1082

    Article  CAS  Google Scholar 

  27. Kauff ND, Domchek SM, Friebel TM et al (2008) Risk reducing salpino-oophorectomy for the prevention of BRCA1- and BRCA2-associated Breast and Gynecologic Cancer: A multicenter, prospective Study. J Clin Oncol 26:1331–1337

    Article  PubMed  Google Scholar 

  28. Pierce LJ, Levin AM, Rebbeck TR, Ben-David MA et al (2006) Ten-year multi-institutional results of breast conserbing surgery and radiotherapy in BRCA1/2-associated stageI/II breast Cancer. J Clin Oncol 24:2437–2443

    Article  PubMed  Google Scholar 

  29. Domchek SM, Friebel TM, Neuhausen SL et al (2006) Mortality after bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers: a prospective cohort study. Lancet 7:223–229

    Article  CAS  Google Scholar 

  30. Turner N, Tutt A, Ashworth A (2005) Targeting the DNA repair defect of BRCA tumours. Curr Opin Pharmacol 5:388–393

    Article  CAS  PubMed  Google Scholar 

  31. Cass I, Baldwin RL, Varkey T et al (2003) Improved survival in women with BRCA-associated ovarian carcinoma. Cancer 97:2187–2195

    Article  CAS  PubMed  Google Scholar 

  32. Kennedy RD, Quinn JE, Mullan PB et al (2004) The role of BRCA1 in the cellular response to chemotherapy. J Natl Cancer Inst 96:1659–1668

    Article  CAS  PubMed  Google Scholar 

  33. Farmer H, McCabe N, Lord CJ et al (2005) targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434:917–921

    Article  CAS  PubMed  Google Scholar 

  34. Bryant HE, Schultz N, Thomas HD et al (2005) Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434:913–917

    Article  CAS  PubMed  Google Scholar 

  35. Graeser MK, Engel C, Rhiem K et al (2009) Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 27:5887–5892

    Article  PubMed  Google Scholar 

Download references

Interessenkonflikt

Die korrespondierende Autorin gibt an, dass kein Interessenkonflikt besteht.

Author information

Authors and Affiliations

  1. Zentrum für Familiären Brust- und Eierstockkrebs, Universitätsklinikum Köln, Kerpener Str. 34, 50931, Köln, Deutschland

    K. Rhiem & R.K. Schmutzler

Authors
  1. K. Rhiem
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R.K. Schmutzler
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K. Rhiem.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rhiem, K., Schmutzler, R. Das familiäre Mammakarzinom. Gynäkologe 43, 79–86 (2010). https://doi.org/10.1007/s00129-009-2506-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00129-009-2506-8

Schlüsselwörter

Keywords

Search

Navigation