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Frauenheilkunde up2date 2011; 5(06): 369-380
DOI: 10.1055/s-0031-1283842
Allgemeine Gynäkologie und gynäkologische Onkologie
© Georg Thieme Verlag KG Stuttgart · New York

Hereditäre Mamma- und Genitalkarzinome

K. Rhiem
,
R. K. Schmutzler
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Publication Date:
01 December 2011 (online)

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Kernaussagen

  • Bei 5 % aller Mammakarzinome bzw. Dickdarmkarzinome liegt ein monogener Erbgang zugrunde.

  • Wird eine BRCA-Mutation nachgewiesen, besteht ein Erkrankungsrisiko von ca. 85 % für ein Mamma- und von ca. 40 % für ein Ovarialkarzinom.

  • Trägerinnen einer pathogenen Mutation in einem der 4 MMR-Gene haben ein Lebenszeitrisiko von 40 – 80 % für ein kolorektales Karzinom, von 40 – 60 % für ein Endometriumkarzinom und von 10 – 126 % für ein Ovarialkarzinom.

  • Statistisch gesehen kann bei 50 % der Ratsuchenden aus einer positiv getesteten Familie eine Mutation durch eine prädiktive Testung ausgeschlossen und damit eine Entlastung ausgesprochen werden.

  • Die prophylaktische beidseitige Salpingo-Oophorektomie ist bei BRCA-Mutationsträgerinnen ab dem 40. Lebensjahr bzw. 5 Jahre vor dem jüngsten Ersterkrankungsalter an Eierstockkrebs in der Familie indiziert.

  • Die Beratung über eine prophylaktische beidseitige Mastektomie bei BRCA-Mutationsträgerinnen sollte nicht-direktiv erfolgen und die Optionen der Sofortrekonstruktion beinhalten.

  • In der Beratung über eine kontralaterale prophylaktische Mastektomie bei erkrankten BRCA-Mutationsträgerinnen sollten das betroffene Gen, Ersterkrankungsalter und Erkrankungsprognose berücksichtigt werden.

 

  • Literatur

  • 1 Robert-Koch-Institut und die Gesellschaft der epidemiologischen Krebsregister in Deutschland e. V.. Krebs in Deutschland 2005 / 2006. Häufigkeiten und Trends. Berlin: 2010 7.. Aufl.
    Google Scholar
  • 2 Miki Y, Swensen J, Shattuck-Eidens D et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 1994; 266: 66-71
    CrossrefPubMedGoogle Scholar
  • 3 Wooster R, Bignell G, Lancaster J et al. Identification of the breast cancer susceptibility gene BRCA2. Nature 1995; 378: 789-792
    CrossrefPubMedGoogle Scholar
  • 4 Walsh T, Lee MK, Casadei S et al. Detection of inherited mutations for breast and ovarian cancer using genomic capture and massively parallel sequencing. Proc Natl Acad Sci USA 2010; 107: 12629-12633
    CrossrefGoogle Scholar
  • 5 Gruber SB, Thompson WD. Cancer and Steroid Hormone Study Group. A population-based study of endometrial cancer and familial risk in younger women. Cancer Epidemiol Biomarkers Prev 1996; 5: 411-417
    Google Scholar
  • 6 Schmutzler RK, Löffler M, Windeler J et al. Familiärer Brust- und Eierstockkrebs: Von der Forschung zur Regelversorgung. Dtsch Arztebl 2005; 102: A3486 / B-2948 / C-2461
    Google Scholar
  • 7 Meindl A, Ditsch N, Kast K et al. Hereditary breast and ovarian cancer: new genes, new treatments, new concepts. Dtsch Arztebl Int 2011; 108: 323-330
    Google Scholar
  • 8 Muller A, Beckmann C, Westphal G et al. German HNPCC Consortium, Prevalence of the mismatch-repair-deficient phenotype in colonic adenomas arising in HNPCC patients: results of a 5-year follow-up study. Int J Colorectal Dis 2006; 21: 632-641
    CrossrefGoogle Scholar
  • 9 King MC, Marks JH, Mandell JB. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 2003; 302: 643-646
    CrossrefGoogle Scholar
  • 10 Meindl A, Hellebrand H, Wiek C et al. Germline mutations in breast and ovarian cancer pedigrees establish RAD51C as a human cancer susceptibility gene. Nat Genet 2010; 42: 410-414
    CrossrefGoogle Scholar
  • 11 Levy-Lahad E. Fanconi anemia and breast cancer susceptibility meet again. Nat Genet 2010; 42: 368-369
    CrossrefGoogle Scholar
  • 12 Weischer M, Bojesen SE, Ellervik C et al. CHEK2*1100delC genotyping for clinical assessment of breast cancer risk: meta-analyses of 26 000 patient cases and 27 000 controls. J Clin Oncol 2008; 26: 542-548
    CrossrefGoogle Scholar
  • 13 Dufault MR, Betz B, Wappenschmidt B et al. Limited relevance of the CHEK2 gene in hereditary breast cancer. Int J Cancer 2004; 110: 320-325
    CrossrefGoogle Scholar
  • 14 Turnbull C, Rahman N. Genetic predisposition to breast cancer: past, present, and future. Annu Rev Genomics Hum Genet 2008; 9: 321-345
    CrossrefGoogle Scholar
  • 15 Easton DF, Pooley KA, Dunning AM et al. Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 2007; 447: 1087-1093
    CrossrefGoogle Scholar
  • 16 Hampel H, Frankel W, Panescu J et al. Screening for Lynch syndrome (hereditary nonpolyposis colorectal cancer) among endometrial cancer patients. Cancer Res 2006; 66: 7810-7817
    CrossrefGoogle Scholar
  • 17 Ollikainen M, Abdel-Rahman WM, Moisio AL et al. Molecular analysis of familial endometrial carcinoma: a manifestation of hereditary nonpolyposis colorectal cancer or a separate syndrome?. J Clin Oncol 2005; 23: 4609-4616
    CrossrefGoogle Scholar
  • 18 Goodfellow PJ, Buttin BM, Herzog TJ et al. Prevalence of defective DNA mismatch repair and MSH6 mutation in an unselected series of endometrial cancers. Proc Natl Acad Sci USA 2003; 100: 5908-5913
    CrossrefGoogle Scholar
  • 19 Woods MO, Williams P, Careen A et al. A new variant database for mismatch repair genes associated with Lynch syndrome. Hum Mutat 2007; 28: 669-673
    CrossrefGoogle Scholar
  • 20 Peltomaki P. Lynch syndrome genes. Fam Cancer 2005; 4: 227-232
    CrossrefGoogle Scholar
  • 21 Lu KH, Schorge JO, Rodabaugh KJ et al. Prospective determination of prevalence of Lynch syndrome in young women with endometrial cancer. J Clin Oncol 2001; K25: 5158-5164
    Google Scholar
  • 22 Malander S, Rabech E, Kristoffersson U et al. The contribution of the hereditary nonpolyposis colorectal cancer syndrome to the development of ovarian cancer. Gynecol Oncol 2006; 101: 238-243
    CrossrefGoogle Scholar
  • 23 Vasen HF, Watson P, Mecklin JP et al. New clinical critieria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterol 1999; 116: 1453-1456
    CrossrefGoogle Scholar
  • 24 Umar A, Boland CR, Terdiman JP et al. Revised Bethesda Guidelines for hereditary nonpolyposis colorectal cancer (Lynch syndrome) and microsatellite instability. J Natl Cancer Inst 2004; 96: 261-268
    CrossrefGoogle Scholar
  • 25 Hemminki K, Dong C, Vaittinin P. Familial risks in cervical cancer: is there a hereditary component?. Int J Cancer 1999; 82: 775-781
    CrossrefGoogle Scholar
  • 26 Hussain SK, Sundquist J, Hemminki K. Familial clustering of cancer at human papillomavirus-associated sites according to the Swedish Family-Cancer Database. Int J Cancer 2008; 122: 1873-1878
    Google Scholar
  • 27 Lakhani SR, Reis-Filho JS, Fulford L et al. Prediction of BRCA1status in patients with breast cancer using estrogen receptor and basal phenotype. Clin Cancer Res 2005; 11: 5175-5180
    CrossrefGoogle Scholar
  • 28 Dent R, Trudeau M, Pritchard KI et al. Triple-negative breast cancer: clinical features and patterns of recurrence. Clin Cancer Res 2007; 13: 4429-4434
    CrossrefPubMedGoogle Scholar
  • 29 Turner NC, Reis-Filho JS. Basal-like breast cancer and the BRCA1 phenotype. Oncogene 2006; 25: 5846-5853
    CrossrefGoogle Scholar
  • 30 Honrado E, Benitez J, Palacios J. The molecular pathology of hereditary breast cancer: Genetic testing and therapeutic implications. Mod Pathol 2005; 18: 1305-1320
    CrossrefGoogle Scholar
  • 31 Foulkes WD, Stefansson IM, Chappuis PO et al. Germline BRCA1 mutations and a basal epithelial phenotype in breast cancer. J Natl Cancer Inst 2003; 95: 1482-1485
    CrossrefGoogle Scholar
  • 32 Schmutzler RK, Rhiem K, Breuer P et al. Outcome of a structured surveillance programme in women with a familial predisposition for breast cancer. Eur J Cancer Prev 2006; 15: 483-489
    CrossrefGoogle Scholar
  • 33 Heywang-Köbrunner SH, Schreer I, Heindel W et al. Imaging studies for the early detection of breast cancer. Dtsch Arztebl 2008; 105: 541-547
    Google Scholar
  • 34 Rhiem K, Flucke U, Schmutzler RK. BRCA1-associated Breast carcinomas frequently present with benign sonographic features. Am J Roentgenol 2006; 185: E11-E12
    Google Scholar
  • 35 Bosse K, Rhiem K, Wappenschmidt B et al. Screening for ovarian cancer by transvaginal ultrasound and serum CA125 measurement in women with a familial predisposition: a prospective cohort study. Gynecol Oncol 2006; 103: 1077-1082
    CrossrefGoogle Scholar
  • 36 Graeser MK, Engel C, Rhiem K et al. Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 2009; 27: 5887-5892
    CrossrefGoogle Scholar
  • 37 Tilanus-Linthorst MM, Alves C, Seynaeve C et al. Contralateral recurrence and prognostic factors in familial non-BRCA1 / 2-associated breast cancer. Br J Surg 2006; 93: 961-968
    CrossrefGoogle Scholar
  • 38 Kauff ND, Domchek SM, Friebel TM et al. Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter, prospective study. J Clin Oncol 2008; 26: 1331-1337
    CrossrefGoogle Scholar
  • 39 Metcalfe KA, Lubinski J, Ghadirian P et al. Predictors of contra-lateral prophylactic mastectomy in women with a BRCA1 or BRCA2 mutation: The Hereditary Breast Cancer Clinical Study Group. J Clin Oncol 2008; 26: 1093-1097
    CrossrefGoogle Scholar
  • 40 Rebbeck TR, Friebel T, Lynch HAT. The PROSE Study Group. Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Clin Oncol 2004; 22: 1055-1062
    CrossrefGoogle Scholar
  • 41 Domchek SM, Friebel TM, Singer CF et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. J Am Med Assoc 2010; 304: 967-975
    CrossrefGoogle Scholar
  • 42 Byrski T, Gronwald J, Huzarski T et al. Pathologic complete response rates in young women with BRCA1-positive breast cancers after neoadjuvant chemotherapy. J Clin Oncol 2010; 28: 375-379
    CrossrefGoogle Scholar
  • 43 Byrski T, Huzarski T, Dent R et al. Response to neoadjuvant therapy with cisplatin in BRCA1-positive breast cancer patients. Breast Cancer Res Treat 2009; 115: 359-363
    CrossrefGoogle Scholar
  • 44 Silver DP, Richardson AL, Eklund AC et al. Efficacy of neoadjuvant Cisplatin in triple-negative breast cancer. J Clin Oncol 2010; 28: 1145-1153
    CrossrefGoogle Scholar
  • 45 Lafarge S, Sylvain V, Ferrara M et al. Inhibition of BRCA1 leads to increased chemoresistance to microtubule-interfering agents, an effect that involves the JNK pathway. Oncogene 2001; 20: 6597-6606
    CrossrefGoogle Scholar
  • 46 Quinn JE, Kennedy RD, Mullan P et al. BRCA1 functions as a differential modulator of chemotherapy-induced apoptosis. Cancer Res 2003; 63: 6221-6228
    Google Scholar
  • 47 Helleday T. The underlying mechanism for the PARP and BRCA synthetic lethality: clearing up the misunderstandings. Mol Oncol 2011; 5: 387-393
    CrossrefPubMedGoogle Scholar
  • 48 Stoffel E, Mukherjee B, Raymond VM et al. Calculation of risk of colorectal and endometrial cancer among patients with Lynch syndrome. Gastroenterol 2009; 137: 1621-1627
    CrossrefGoogle Scholar
  • 49 Aarnio M, Sankila R, Pukkala E et al. Cancer risk in mutation carriers of DNA-mismatch-repair genes. Int J Cancer 1999; 81: 214-218
    CrossrefGoogle Scholar
  • 50 Vasen HF, Wijnen JT, Menko FH et al. Cancer risk in families with hereditary nonpolyposis colorectal cancer diagnosed by mutation analysis. Gastroenterol 1996; 110: 1020-1027
    CrossrefGoogle Scholar
  • 51 Walsh MD, Buchanan DD, Cummings MC et al. Lynch syndrome-associated breast cancers: clinicopathologic characteristics of a case series from the colon cancer family registry. Clin Cancer Res 2010; 16: 2214-2224
    CrossrefGoogle Scholar
  • 52 Barrow E, Robinson L, Alduaij W et al. Cumulative lifetime incidence of extracolonic cancers in Lynch syndrome: a report of 121 families with proven mutations. Clin Genet 2009; 75: 141-149
    CrossrefPubMedGoogle Scholar
  • 53 Watson P, Butzow R, Lynch HT et al. The clinical features of ovarian cancer in hereditary nonpolyposis colorectal cancer. Gynecol Oncol 2001; 82: 223-228
    CrossrefGoogle Scholar
  • 54 Watson P, Lin KM, Rodriguez-Bigas MA et al. Colorectal carcinoma survival among hereditary nonpolyposis colorectal carcinoma family members. Cancer 1998; 83: 259-266
    CrossrefGoogle Scholar
  • 55 Boks DE, Trujillo AP, Voogd AC et al. Survival analysis of endometrial carcinoma associated with hereditary nonpolyposis colorectal cancer. Int J Cancer 2002; 102: 198-200
    CrossrefGoogle Scholar
  • 56 Manchanda R, Menon U, Michaelson-Cohen R et al. Hereditary non-polyposis colorectal cancer or Lynch syndrome: the gynecological perspective. Curr Opin Ostet Gynecol 2009; 21: 31-38
    Google Scholar
  • 57 Lu KH, Dinh M, Kohlmann W et al. Gynecologic cancer as a sentinel cancer for women with hereditary nonpolyposis colorectal cancer syndrome. Obstet Gynecol 2005; 105: 569-574
    CrossrefGoogle Scholar
  • 58 Jarvinen HJ, Aarnio M, Mustonen H et al. Controlled 15-year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer. Gastroenterol 2000; 118: 829-834
    CrossrefGoogle Scholar
  • 59 Schmeler KM, Lynch HT, Chen LM et al. Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med 2006; 354: 261-269
    CrossrefGoogle Scholar
  • 60 Lindor NM, Petersen GM, Hadley DW et al. Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review. J Am Med Assoc 2006; 296: 1507-1517
    CrossrefGoogle Scholar