Skip to main content

Advertisement

Log in

Risk-reducing salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers

  • Gynecologic Oncology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Background

Risk-reducing salpingo-oophorectomy (RRSO) is often recommended to carriers of deleterious breast cancer gene 1/2 (BRCA1/2) mutations in order to reduce their breast cancer risk by 50% and their ovarian cancer risk by approximately 95%. To evaluate the acceptance, timing, histopathology findings and follow-up results we retrospectively analyzed a cohort of BRCA1/2 mutation carriers who underwent risk-reducing salpingo-oophorectomies.

Methods

Between 1996 and 2009, 306 women who tested positive for a BRCA1 or BRCA2 mutation were counseled for preventive options. RRSO was recommended to all mutation carriers at age 40 or 5 years prior to the earliest occurrence of ovarian cancer in the family. Data from 175 BRCA mutation carriers (92 BRCA1 and 83 BRCA2), who decided to undergo a RRSO, were analyzed. Data were collected from study entry until recent follow-up.

Results

Fifty-seven percent of BRCA mutation carriers opted for RRSO. Mean age at time of surgery was 47 years. Overall, one occult carcinoma of the fallopian tube was detected at the time of surgery in a 57-year-old woman and one primary peritoneal carcinoma occurred 26 months after RRSO in a 59-year-old woman.

Conclusion

Risk-reducing salpingo-oophorectomy is widely accepted. Recommendation of surgery at the age of 40 seems to be safe and the frequency of extraovarian primary peritoneal carcinoma after surgery is low.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, Bishop DT, Weber B, Lenoir G, Chang-Claude J, Sobol H, Teare MD, Struewing J, Arason A, Scherneck S, Peto J, Rebbeck TR, Tonin P, Neuhausen S, Barkardottir R, Eyfjord J, Lynch H, Ponder BA, Gayther SA, Zelada-Hedman M et al (1998) Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet 62:676–689

    Article  CAS  PubMed  Google Scholar 

  2. Struewing JP, Hartge P, Wacholder S, Baker SM, Berlin M, McAdams M, Timmerman MM, Brody LC, Tucker MA (1997) The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med 336:1401–1408

    Article  CAS  PubMed  Google Scholar 

  3. Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Kwan E, Jack E, Vesprini DJ, Kuperstein G, Abrahamson JL, Fan I, Wong B, Narod SA (2001) Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet 68:700–710

    Article  CAS  PubMed  Google Scholar 

  4. King MC, Marks JH, Mandell JB, New York Breast Cancer Study Group (2003) Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science 302:643–646

    Article  CAS  PubMed  Google Scholar 

  5. Antoniou A, Pharoah PD, Narod S, Risch HA, Eyfjord JE, Hopper JL, Loman N, Olsson H, Johannsson O, Borg A, Pasini B, Radice P, Manoukian S, Eccles DM, Tang N, Olah E, Anton-Culver H, Warner E, Lubinski J, Gronwald J, Gorski B, Tulinius H, Thorlacius S, Eerola H, Nevanlinna H, Syrjäkoski K, Kallioniemi OP, Thompson D, Evans C, Peto J, Lalloo F, Evans DG, Easton DF (2003) Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72:1117–1130

    Article  CAS  PubMed  Google Scholar 

  6. Antoniou AC, Pharoah PD, Easton DF, Evans DG (2006) BRCA1 and BRCA2 cancer risks. J Clin Oncol 24:3312–3313

    Article  PubMed  Google Scholar 

  7. Easton DF, Bishop DT, Ford D, Crockford GP (1993) Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium. Am J Hum Genet 52:678–701

    CAS  PubMed  Google Scholar 

  8. Finch A, Beiner M, Lubinski J, Lynch HT, Moller P, Rosen B, Murphy J, Ghadirian P, Friedman E, Foulkes WD, Kim-Sing C, Wagner T, Tung N, Couch F, Stoppa-Lyonnet D, Ainsworth P, Daly M, Pasini B, Gershoni-Baruch R, Eng C, Olopade OI, McLennan J, Karlan B, Weitzel J, Sun P, Narod SA, Hereditary Ovarian Cancer Clinical Study Group (2006) Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 mutation. JAMA 296:185–192

    Article  CAS  PubMed  Google Scholar 

  9. Anglian Breast Cancer Study Group (2000) Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. Br J Cancer 83:1301–1308

    Article  Google Scholar 

  10. Satagopan JM, Boyd J, Kauff ND, Robson M, Scheuer L, Narod S, Offit K (2002) Ovarian cancer risk in Ashkenazi Jewish carriers of BRCA1 and BRCA2 mutations. Clin Cancer Res 8:3776–3781

    CAS  PubMed  Google Scholar 

  11. Boyd J, Sonoda Y, Federici MG, Bogomolniy F, Rhei E, Maresco DL, Saigo PE, Almadrones LA, Barakat RR, Brown CL, Chi DS, Curtin JP, Poynor EA, Hoskins WJ (2000) Clinicopathologic features of BRCA-linked and sporadic ovarian cancer. JAMA 283:2260–2265

    Article  CAS  PubMed  Google Scholar 

  12. Bosse K, Rhiem K, Wappenschmidt B, Hellmich M, Madeja M, Ortmann M, Mallmann P, Schmutzler R (2006) Screening for ovarian cancer by transvaginal ultrasound and serum CA125 measurement in women with a familial predisposition: a prospective cohort study. Gynecol Oncol 103:1077–1082

    Article  CAS  PubMed  Google Scholar 

  13. Jacobs I (2005) Screening for familial ovarian cancer: the need for well-designed prospective studies. J Clin Oncol 23:5443–5445

    Article  PubMed  Google Scholar 

  14. Rebbeck TR, Lynch HT, Neuhausen SL, Narod SA, Van’t Veer L, Garber JE, Evans G, Isaacs C, Daly MB, Matloff E, Olopade OI, Weber BL, Prevention and Observation of Surgical End Points Study Group (2002) Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 346:1616–1622

    Article  PubMed  Google Scholar 

  15. Kauff ND, Satagopan JM, Robson ME, Scheuer L, Hensley M, Hudis CA, Ellis NA, Boyd J, Borgen PI, Barakat RR, Norton L, Castiel M, Nafa K, Offit K (2002) Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 346:1609–1615

    Article  PubMed  Google Scholar 

  16. Domchek SM, Friebel TM, Neuhausen SL, Wagner T, Evans G, Isaacs C, Garber JE, Daly MB, Eeles R, Matloff E, Tomlinson GE, Van’t Veer L, Lynch HT, Olopade OI, Weber BL, Rebbeck TR (2006) Mortality after bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers: a prospective cohort study. Lancet Oncol 7:223–229

    Article  CAS  PubMed  Google Scholar 

  17. Kauff ND, Domchek SM, Friebel TM, Robson ME, Lee J, Garber JE, Isaacs C, Evans DG, Lynch H, Eeles RA, Neuhausen SL, Daly MB, Matloff E, Blum JL, Sabbatini P, Barakat RR, Hudis C, Norton L, Offit K, Rebbeck TR (2008) Risk-reducing salpingo-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 

  18. Rutter JL, Wacholder S, Chetrit A, Lubin F, Menczer J, Ebbers S, Tucker MA, Struewing JP, Hartge P (2003) Gynecologic surgeries and risk of ovarian cancer in women with BRCA1 and BRCA2 Ashkenazi founder mutations: an Israeli population-based case-control study. J Natl Cancer Inst 95:1072–1078

    Article  PubMed  Google Scholar 

  19. Rebbeck TR, Levin AM, Eisen A, Snyder C, Watson P, Cannon-Albright L, Isaacs C, Olopade O, Garber JE, Godwin AK, Daly MB, Narod SA, Neuhausen SL, Lynch HT, Weber BL (1999) Breast cancer risk after bilateral prophylactic oophorectomy in BRCA1 mutation carriers. J Natl Cancer Inst 91:1475–1479

    Article  CAS  PubMed  Google Scholar 

  20. Kramer JL, Velazquez IA, Chen BE, Rosenberg PS, Struewing JP, Greene MH (2005) Prophylactic oophorectomy reduces breast cancer penetrance during prospective, long-term follow-up of BRCA1 mutation carriers. J Clin Oncol 23:8629–8635

    Article  PubMed  Google Scholar 

  21. Chang-Claude J, Andrieu N, Rookus M, Brohet R, Antoniou AC, Peock S, Davidson R, Izatt L, Cole T, Noguès C, Luporsi E, Huiart L, Hoogerbrugge N, Van Leeuwen FE, Osorio A, Eyfjord J, Radice P, Goldgar DE, Easton DF, Epidemiological Study of Familial Breast Cancer (EMBRACE), Gene Etude Prospective Sein Ovaire (GENEPSO), Genen Omgeving Studie van de Werkgroep Hereditiair Borstkanker Onderzoek Nederland (GEO-HEBON), International BRCA1/2 Carrier Cohort Study (IBCCS) Collaborators Group (2007) Age at menarche and menopause and breast cancer risk in the International BRCA1/2 Carrier Cohort Study. Cancer Epidemiol Biomarkers Prev 16:740–746

    Google Scholar 

  22. Eisen A, Lubinski J, Klijn J, Moller P, Lynch HT, Offit K, Weber B, Rebbeck T, Neuhausen SL, Ghadirian P, Foulkes WD, Gershoni-Baruch R, Friedman E, Rennert G, Wagner T, Isaacs C, Kim-Sing C, Ainsworth P, Sun P, Narod SA (2005) Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case-control study. J Clin Oncol 23:7491–7496

    Article  PubMed  Google Scholar 

  23. Meindl A (2002) Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population. Int J Cancer 97:472–480

    Article  CAS  PubMed  Google Scholar 

  24. Schmutzler RK, Rhiem K, Breuer P, Wardelmann E, Lehnert M, Coburger S, Wappenschmidt B (2006) Outcome of a structured surveillance programme in women with a familial predisposition for breast cancer. Eur J Cancer Prev 15:483–489

    Article  PubMed  Google Scholar 

  25. Colgan TJ, Murphy J, Cole DE et al (2001) Occult carcinoma in prophylactic oophorectomy specimens: prevalence and association with BRCA germline mutation status. Am J Surg Pathol 25:1283–1289

    Article  CAS  PubMed  Google Scholar 

  26. Kauff ND, Barakat RR (2007) Risk-reducing salpingo-oophorectomy in patients with germline mutations in BRCA1 or BRCA2. J Clin Oncol 25:2921–2927

    Article  CAS  PubMed  Google Scholar 

  27. 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 

  28. Lu KH, Garber JE, Cramer DW, Welch WR, Niloff J, Schrag D, Berkowitz RS, Muto MG (2000) Occult ovarian tumors in women with BRCA1 or BRCA2 mutations undergoing prophylactic oophorectomy. J Clin Oncol 18:2728–2732

    CAS  PubMed  Google Scholar 

  29. Powell CB, Kenley E, Chen LM, Crawford B, McLennan J, Zaloudek C, Komaromy M, Beattie M, Ziegler J (2005) Risk-reducing salpingooophorectomy in BRCA mutation carriers: role of serial sectioning in the detection of occult malignancy. J Clin Oncol 23:127–132

    Article  PubMed  Google Scholar 

  30. Rabban JT, Crawford B, Chen LM, Powell CB, Zaloudek CJ (2009) Transitional cell metaplasia of fallopian tube fimbriae: a potential mimic of early tubal carcinoma in risk reduction salpingo-oophorectomies from women with BRCA mutations. Am J Surg Pathol 33:111–119

    Article  PubMed  Google Scholar 

  31. Medeiros F, Muto MG, Lee Y, Elvin JA, Callahan MJ, Feltmate C, Garber JE, Cramer DW, Crum CP (2006) The tubal fimbria is a preferred site for early adenocarcinoma in women with familial ovarian cancer syndrome. Am J Surg Pathol 30:230–236

    Article  PubMed  Google Scholar 

  32. Narod SA, Sun P, Ghadirian P, Lynch H, Isaacs C, Garber J, Weber B, Karlan B, Fishman D, Rosen B, Tung N, Neuhausen SL (2001) Tubal ligation and risk of ovarian cancer in carriers of BRCA1 or BRCA2 mutations: a case-control study. Lancet 357:1467–1470

    Article  CAS  PubMed  Google Scholar 

  33. Antoniou AC, Rookus M, Andrieu N, Brohet R, Chang-Claude J, Peock S, Cook M, Evans DG, Eeles R, EMBRACE, Nogues C, Faivre L, Gesta P, GENEPSO, van Leeuwen FE, Ausems MG, Osorio A, GEO-HEBON, Caldes T, Simard J, Lubinski J, Gerdes AM, Olah E, Fürhauser C, Olsson H, Arver B, Radice P, Easton DF, Goldgar DE (2009) Reproductive and hormonal factors, and ovarian cancer risk for BRCA1 and BRCA2 mutation carriers: results from the International BRCA1/2 Carrier Cohort Study. Cancer Epidemiol Biomarkers Prev 18:601–610

    Article  CAS  PubMed  Google Scholar 

  34. Rebbeck TR, Kauff ND, Domchek SM (2009) Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst 101:80–87

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by a grant from the German Cancer Aid to RKS (No. 107054). The documentation assistance by Astrid Sauerbruch and Petra Wihler and the technical assistance by Brigitte Kau, Gaby Krebsbach and Juliane Köhler are gratefully acknowledged. We thank all the families who took part in the program of the Centre for Hereditary Breast and Ovarian Cancer Cologne.

Conflict of interest statement

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rita K. Schmutzler.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rhiem, K., Foth, D., Wappenschmidt, B. et al. Risk-reducing salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers. Arch Gynecol Obstet 283, 623–627 (2011). https://doi.org/10.1007/s00404-010-1476-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00404-010-1476-3

Keywords

Navigation