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Prophylaktische Chirurgie des Mamma- und Ovarialkarzinoms

Prophylactic surgery of mammary and ovarian carcinoma

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Zusammenfassung

In den vergangenen Jahren konnten neue Erkenntnisse über die genetischen Grundlagen der Karzinogenese infolge moderner molekular-biologischer Techniken gewonnen werden. Zahlreiche prädisponierende Gene wurden bereits beschrieben. Das hereditäre Mamma- und Ovarialkarzinomsyndrom (Mutationen in den BRCA1/2-Genen) als auch das Endometriumkarzinom in Zusammenhang mit dem hereditären Nonpolyposis-Kolonkarzinom- (HNPCC-)Syndrom sind die häufigsten hereditären Karzinome im Bereich der Gynäkologie. Mutationen in TP53 (Li-Fraumeni-Syndrom) und PTEN (Cowden-Syndrom) sind mit einem erhöhten Mammakarzinomrisiko assoziiert, jedoch jeweils nur für einen kleinen Teil der hereditären Mammakarzinome verantwortlich.

Die Vererbungswahrscheinlichkeit und das Erkrankungsrisiko können durch die Erhebung des Familienstammbaumes, Nutzung von Risikoberechnungsprogrammen und Durchführung genetischer Analysen näher identifiziert und definiert werden. Folgend können Maßnahmen der primären, sekundären und tertiären Prävention eingeleitet werden. Die einzige Maßnahme, welche das Erkrankungsrisiko bei Vorliegen einer Mutation in den prädisponierenden Genen nachweislich senken konnte, ist aktuell die prophylaktische Chirurgie.

Abstract

New insights into the genetic basis of carcinogenesis have been obtained by modern molecular biological techniques. Several susceptibility genes are known. The hereditary breast and ovarian cancer syndrome (germline mutations in BRCA1 and BRCA2) and endometrial cancer in the context of the hereditary nonpolyposis colorectal cancer syndrome (HNPCC), germline mutations in mismatch-repair genes, are the most frequent hereditary cancer syndromes in gynaecology. Mutations in TP53 (Li-Fraumeni syndrome) and PTEN (Cowden’s disease), associated with increased risk of breast cancer, are responsible for a smaller portion of familial breast cancer.The risk of inheritance and disease can be identified and defined by investigating family history, risk calculation programs, and genetic testing. Afterwards, options of primary, secondary, and tertiary prevention can be formulated. Presently, prophylactic surgery is the only option proven by clinical trials that can reduce the mortality of hereditary breast and ovarian cancer.

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Literatur

  1. Beckmann MW, Fasching PA, Lux MP et al. (2001) Das familiäre Mammakarzinom-Syndrom: prädiktive genetische Testung, Beratung und Betreuung. Med Welt 52:385–390

    Google Scholar 

  2. Fasching PA, Lux MP, Bani M, Beckmann MW (2004) Hereditäres Mamma- und Ovarialkarzinom — ein Update. Teil I — molekulare Grundlagen, Tumorrisikoberatung und Risikoberechnung. Geburtsh Frauenheilk 64:900–911

    Article  Google Scholar 

  3. Lux MP, Fasching PA, Beckmann MW (2005) Hereditary breast and ovarian cancer: review and future perspectives. J Mol Med (in press)

    Google Scholar 

  4. Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, King MC (1990) Linkage of early-onset familial breast cancer to chromosome 17q21. Science 250:1684–1689

    PubMed  Google Scholar 

  5. Wooster R, Neuhausen SL, Mangion J et al. (1994) Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12–13. Science 265:2088–2090

    PubMed  Google Scholar 

  6. Beckmann MW, Lux MP (2004) Hereditäres Mammakarzinom — Prädiktive Diagnostik und präventive Chirurgie. Onkologe 10(1):20–28

    Article  Google Scholar 

  7. Easton DF (2002) Familial risks of breast cancer. Breast Cancer Res 4(5):179–181

    Article  PubMed  Google Scholar 

  8. Easton DF, Breast Cancer Linkage Consortium (2003) Familial breast cancer risks and the BCLC database. The Breast Cancer Linkage Consortium (BCLC) and the International Collaborative Group on Familial Breast and Ovarian Cancer (ICG-FBOC) 14th General Meeting, Madrid, June 2nd–4th

  9. Haffty BG, Harrold E, Khan AJ et al. (2002) Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status. Lancet 359(9316):1471–1477

    Article  PubMed  Google Scholar 

  10. Boyd J (2001) Molecular genetics of hereditary ovarian cancer. In: Rubin SC, Sutton GP (Hrsg) Ovarian cancer. Vol 2. Lippincott Williams & Wilkins, Philadelphia, S 3–17

  11. Breast Cancer Linkage Consortium (1999) Cancer risks in BRCA2 mutation carriers. J Natl Cancer Inst 91:1310–1316

    Article  PubMed  Google Scholar 

  12. Thompson D, Easton DF, Breast Cancer Linkage Consortium (2002) Cancer incidence in BRCA1 mutation carriers. J Natl Cancer Inst 94:1358–1365

    PubMed  Google Scholar 

  13. Lakhani SR, van de Vijver MJ, Jacqemier J, Anderson TJ, Osin PP, McGuffog L, Easton DF (2002) The pathology of familial breast cancer: predictive value of immunohistochemical markers estrogen receptor, progesterone receptor, Her-2, and p53 in patients with mutations in BRCA1 and BRCA2. J Clin Oncol 20:2310–2318

    Article  PubMed  Google Scholar 

  14. Lakhani SR (2003) The pathology of familial breast cancer. The Breast Cancer Linkage Consortium (BCLC) and the International Collaborative Group on Familial Breast and Ovarian Cancer (ICG-FBOC). 14th General Meeting, Madrid, June 2nd–4th

  15. Lakhani SR, Reis-Filho JS, Fulford L et al., Breast Cancer Linkage Consortium (2005) Prediction of BRCA1 Status in Patients with Breast Cancer Using Estrogen Receptor and Basal Phenotype. Clin Cancer Res 11 (14):5175–5180

    Article  PubMed  Google Scholar 

  16. Pharoah PD, Easton DF, Stockton DL, Gayther S, Ponder BA (1999) Survival in familial, BRCA1-associated, and BRCA2-associated epithelial ovarian cancer. United Kingdom Coordinating Committee for Cancer Research (UKCCCR) Familial Ovarian Cancer Study Group. Cancer Res 59:868–871

    PubMed  Google Scholar 

  17. Cass I, Baldwin RL, Varkey T, Moslehi R, Narod SA, Karlan BY (2003) Improved survival in women with BRCA-associated ovarian carcinoma. Cancer 97(9):2187–2195

    Article  PubMed  Google Scholar 

  18. Levine DA, Frederici MG, Reuter VE, Boyd J (2002) Cell proliferation and apoptosis in BRCA-associated hereditary ovarian cancer. Gynecol Oncol 85:431–434

    Article  PubMed  Google Scholar 

  19. Foulkes WD, Wong N, Brunet JS et al. (1997) Germ-line BRCA1 mutation is an adverse prognostic factor in Ashkenazi Jewish women with breast cancer. Clin Cancer Res 3:2465–2469

    PubMed  Google Scholar 

  20. Ansquer Y, Gautier C, Fourquet A et al. (1998) Survival in early-onset BRCA1 breast-cancer patients. Lancet 352:541

    Article  Google Scholar 

  21. Robson M, Levin D, Federici M et al. (1999) Breast conservation therapy for invasive breast cancer in Ashkenazi women with BRCA gene founder mutations. J Natl Cancer Inst 91:2112–2117

    Article  PubMed  Google Scholar 

  22. Stoppa-Lyonnet D, Ansquer Y, Dreyfus H et al. (2000) Familial invasive breast cancers: worse outcome related to BRCA1-mutations. J Clin Oncol 18:4053–4059

    PubMed  Google Scholar 

  23. Wooster R, Weber BL (2003) Breast and ovarian cancer. N Engl J Med 348:2339–2347

    Article  PubMed  Google Scholar 

  24. Thompson D, Duedal S, Kirner J et al. (2005) Cancer Risks and Mortality in Heterozygous ATM Mutation Carriers. J Nat Cancer Inst 97(11):813–822

    PubMed  Google Scholar 

  25. Lawes DA, SenGupta SB, Boulos PB (2002) Pathogenesis and clinical management of hereditary non-polyposis colorectal cancer. Br J Surg 89(11):1357

    Article  PubMed  Google Scholar 

  26. Beckmannn MW, Fasching PA, Bani MR, Lux MP (2005) Clinical hereditary syndromes in gynaecology. Gynaecol Forum 10(1):12–17

    Google Scholar 

  27. Lux MP, Fasching PA, Bani MR, Löhberg C, Pöhls U, Ackermann S, Beckmann MW (2003) Prophylaktische Therapieoptionen bei Hereditary non-polyposis colorectal cancer (HNPCC)-assozierten gynäkologischen Malignomen. In: Sutter T, Brauckhoff M, Dralle H (Hrsg) Aktuelle Chirurgie endokriner Erkrankungen und hereditärer Tumoren. Gutenberg Verlag und Druckerei GmBH, Leipzig, S 1673–1691

  28. Boks DES, Trujillo AP, Voogd AC, Morreau H, Kenter GG, Vasen HFA (2002) Survival Analysis of Endometral Carcinoma associated with hereditary Nonpolyposis Colorectal Cancer. Int J Cancer 102:198–200

    Article  PubMed  Google Scholar 

  29. Watson P, Bützow R, Lynch HAT et al. and the International Collaborative Group on HNPCC (2001) The Clinical Features of Ovarian Cancer in Hereditary Nonpolyposis Colorectal Cancer. Gynecol Oncol 82:223–228

    Article  PubMed  Google Scholar 

  30. De Jong MM, Nolte IM, te Meermann GJ et al. (2002) Genes other than BRCA1 and BRCA2 involved in breast cancer susceptibility. J Med Genet 39:225–242

    Article  PubMed  Google Scholar 

  31. Lux MP, Fasching PA, Bani MR, Beckmann MW (2004) Hereditäres Mamma- und Ovarialkarzinom — ein Update. Teil II — Therapie, Früherkennung und Prophylaxe. Geburtsh Frauenheilk 64:1037–1051

    Article  Google Scholar 

  32. Amir E, Evans DG, Shenton A et al. (2003) Evaluation of breast cancer risk assessment packages in the family history evaluation and screening programme. J Med Genet 40:807–814

    Article  PubMed  Google Scholar 

  33. Pichert G, Bollinger B, Buser K, Pagani O (2003) Evidence-based management for women at increased breast/ ovarian cancer risk. Ann Oncol 14:9–19

    Article  PubMed  Google Scholar 

  34. Pennisi VR, Capozzi A (1989) Subcutaneous mastectomy data: a final statistical analysis of 1500 patients. Aesthetic Plast Surg 13:15–21

    Article  PubMed  Google Scholar 

  35. Hartmann LC, Schaid DJ, Woods JE et al. (1999) Efficacy of bilateral prophylactic mastectomy in women with family history of breast cancer. N Engl J Med 340:77–84

    Article  PubMed  Google Scholar 

  36. Hartmann LC, Sellers TA, Schaid DJ et al. (2001) Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. J Natl Cancer Inst 93:1633–1642

    Article  PubMed  Google Scholar 

  37. Meijers-Heiboer H, van Geel B, van Puuten WLJ et al. (2001) Breast cancer after prphylactic bliateral mastectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 345:159–164

    Article  PubMed  Google Scholar 

  38. Hoogerbrugge N, Bult P, de Widt-Levert LM et al. (2003) High Prevalence of Premalignant Lesions in Prophylactically Removed Breasts From Women at Hereditary Risk for Breast Cancer. J Clin Oncol 21 (1):41–45

    Article  Google Scholar 

  39. Lostumbo L, Carbine N, Wallace J, Ezzo J (2005) Propyhlactic mastectomy for the prevention of breast cancer. Cochrane Library 2:1–58

    Google Scholar 

  40. Spears SL, Carter ME, Schwarz K (2005) Prophylactic mastectomy: options and reconstructive alternatives. Plast Reconst Surg 115:891–909

    Article  PubMed  Google Scholar 

  41. Hughes KS, Papa MZ, Whitney T, McLellan R (1999) Prophylactic Mastectomy and Inherited Predisposition to Breast Carcinoma. Cancer 86(11):2502–2516

    Article  PubMed  Google Scholar 

  42. Evans DGR, Anderson E, Lallo F et al. (1998) Utilisation of prophylactic mastectomy in 10 European centres. Dis Markers 15:148–151

    Google Scholar 

  43. Al-Ghazal SK, Blamey RW (2000) Subcutaneous mastectomy with implantat reconstruction: cosmetic outcome and patient satisfaction. Eur J Surg Oncol 26:137–141

    Article  PubMed  Google Scholar 

  44. Metcalfe KA, Semple JL, Narod SA (2005) Time to reconsider subcutaneous mastectomy for breast-cancer prevention? Lancet Oncol 6:431–434

    Article  PubMed  Google Scholar 

  45. NIH Consensus Development Panel on Ovarian Cancer (1995) NIH consensus conference. Ovarian cancer. Screening, treatment, and follow up. JAMA 273:491–497

    Article  PubMed  Google Scholar 

  46. Tobacman JK, Greene MH, Tucker MA, Costa J, Kase R, Fraumeni JF Jr (1982) Intra-abdominal carcinomatosis after prophylactic oophorectomy in ovarian-cancer-prone families. Lancet 2(8302):795–797

    Article  PubMed  Google Scholar 

  47. Piver SM, Jishi MF, Tsukada Y, Nava G (1993) Primary peritoneal carcinoma after prophylactic oophorectomy in women with a family history of ovarian cancer. Cancer 71:2751–2755

    PubMed  Google Scholar 

  48. Struewing JP, Watson P, Easton DF, Ponder BA (1999) Prophylactic oophorectomy in inherited breast/ ovarian cancer families. Monogr Natl Cancer Inst 17:33–35

    Google Scholar 

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

    Article  PubMed  Google Scholar 

  50. Rebbeck TR, Lynch HT, Neuhausen SL et al. (2002) Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 346:1616–1622

    Article  PubMed  Google Scholar 

  51. Lu KH, Garber JE, Cramer DW et al. (2000) Occult Ovarian Tumors in Women With BRCA1 or BRCA2 Mutations Undergoing Prophylactic Oophorectomy. J Clin Oncol 18(14):2728–2732

    PubMed  Google Scholar 

  52. Leeper K, Garcia R, Swisher E, Goff B, Greer B, Paley P (2002) Pathologic Findings in Prophylactic Oophorectomy Specimens in High-Risk Women. Gynecol Oncol 87:52–56

    Article  PubMed  Google Scholar 

  53. Powell CB, Kenley E, Chen LM et al. (2005) Risk-Reducing Salpingo-Oophorectomy in BRCA Mutation Carriers: Role of Serial Sectioning in the Detection of Occult Malignancy. Journal of Clinical Oncology 23(1):127–132

    Article  PubMed  Google Scholar 

  54. Nathorst-Boos J, von Schoultz B, Carlstrom K (1993) Elective ovarian removel and estrogen replacement therapy: effects on sexual life, psychological well-being and androgen status. J Psychosom Obstet Gynecol 14:283–293

    Google Scholar 

  55. Beckmann MW, Braendle W, Brucker C et al. (2003) Konsensus-Empfehlung zur Hormontherapie (HT) im Klimakterium und in der Postmenopause. Im Auftrag des Vorstands der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe. Geburtsh Frauenheilk 63(3):209–212

    Article  Google Scholar 

  56. Meijers-Heijbouer H, Brekelmans CTM et al. (2003) Use of genetic testing and prophylactic mastectomy and oophorectomy in women with breast or ovarian cancer from families with a BRCA1 or BRCA2 mutation. J Clin Oncol 21:1675–1681

    Article  PubMed  Google Scholar 

  57. Scheuer L, Kauff N, Robson M et al. (2002) Outcome of Preventive Surgery and Screening for Breast and Ovarian Cancer in BRCA Mutation Carriers. J Clin Oncol 20(5):1260–1268

    Article  PubMed  Google Scholar 

  58. Robson M, Svahn T, McCormick B, Borgen P, Hudis CA, Norton L, Offit K (2005) Appropriateness of Breast-Conserving Treatment of Breast Carcinoma in Women with Germline Mutations in BRCA1 or BRCA2. Cancer 103(1):44–51

    Article  PubMed  Google Scholar 

  59. Haffty BG, Harrold E, Khan AJ et al. (2002) Outcome of conservatively managed early-onset breast cancer by BRCA1/BRCA2 status. Lancet 359:1471–1477

    Article  PubMed  Google Scholar 

  60. Goffin J, Chappuis P, Wong N, Foulkes WD (2001) Magnetic Response Imaging and Mammography in women with hereditary risk of breast cancer. J Natl Cancer Inst 93:1876–1881

    Article  Google Scholar 

  61. Narod SA, Brunet JS, Ghadirian P et al. for the Hereditary Breast Cancer Clinical Study Group (2000) Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study. Lancet 356:1876–1881

    Article  PubMed  Google Scholar 

  62. Møller P, Borg Ǻ, Evans DG et al. (2002) Survival in prospectively ascertained familial Breast Cancer: Analysis of a Series stratified by Tumour Characteristics, BRCA Mutations and Oophoectomy. Int J Cancer 101:555–559

    Article  PubMed  Google Scholar 

  63. Stolier AJ, Fuhrmann GM, Mauterer L, Bolton JS, Superneau DW (2004) Initial experience with surgical treatment planing in the newly diagnosed breast cancer patient at high risk for BRCA1- or BRCA-2 Mutation. Breast J 10:475–480

    Article  PubMed  Google Scholar 

  64. Weitzel JN, McCaffey SM, Nedelcu R, MacDonald DJ, Blazer KR, Culliname CA (2003) Effect of genetic cancer risk assessment on surgical decisions at breast cancer diagnosis. Arch Surg 138:1323–1328

    Article  PubMed  Google Scholar 

  65. Lux MP (2005) BRCA1/2 assoziiertes Mammakarzinom: BET oder Mastektomie? Senologie 2:65–66

    Google Scholar 

  66. Adem C, Reynolds C, Soderberg CL et al. (2003) Pathologic characteristics of breast parenchyma in patients with hereditary breast carcinoma, including BRCA1 and BRCA2 mutation carriers. Cancer 97:1–11

    Article  PubMed  Google Scholar 

  67. Kiechle M, Schmutzler RK, Beckmann MW (2002) Prävention: Familiäres Mamma- und Ovarialkarzinom. Dtsch Ärztebl 99(20):A-1372

    Google Scholar 

  68. Humphrey LJ (1983) Subcutaneous mastectomy is not a prophylaxis against carcinoma of the breast: opinion or knowledge? Am J Surg 145:31–312

    Article  Google Scholar 

  69. Woods JE (1986) Breast reconstruction: current state of the art. Mayo Clin Proc 61:579–585

    PubMed  Google Scholar 

  70. Bohmert HH (1988) Subcutaneous mastectomy. In: Grundfest-Broniatow-ski S, Esseltyn CB jr (eds) Controversies in Breast Disease: Diagnosis and Management. Marcel Dekker, New York, pp 235–259

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  1. Frauenklinik, Universitätsklinikum Erlangen

    M. P. Lux, M. R. Bani, P. A. Fasching & M. W. Beckmann

  2. Frauenklinik, Universitätsklinikum Erlangen, Universitätsstraße 21–23, 91054 , Erlangen

    M. P. Lux

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  1. M. P. Lux
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Lux, M.P., Bani, M.R., Fasching, P.A. et al. Prophylaktische Chirurgie des Mamma- und Ovarialkarzinoms. Chirurg 76, 1145–1154 (2005). https://doi.org/10.1007/s00104-005-1100-4

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