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Prophylactic Mastectomy and Risk-Reducing Salpingo-oophorectomy in BRCA1/2 Mutation Carriers

Abstract

Women with either BRCA1 or BRCA2 germline mutations have a significantly elevated risk of breast and ovarian cancer. Approximately 60 %–70 % of BRCA1 carriers and 45 %–60 % of BRCA2 carriers will develop a breast cancer by age 70, and there is a lower but very significant risk of developing ovarian cancer in both BRCA1 and BRCA2 carriers. This review summarizes data from both retrospective and prospective studies examining the impact of bilateral prophylactic mastectomy and risk-reducing salpingo-oophorectomy on reducing the risk of developing breast and, for the latter, ovarian cancer. In addition, we review data on the mortality benefit from risk-reducing salpino-oophorectomy.

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References

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  1. Struewing JP, Hartge P, Wacholder S, et al. The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews. N Engl J Med. 1997;336:1401–8.

    PubMed  Article  CAS  Google Scholar 

  2. King MC, Marks JH, Mandell JB. Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2. Science. 2003;302:643–6.

    PubMed  Article  CAS  Google Scholar 

  3. Moller P, Borg A, Evans DG, et al. Survival in prospectively ascertained familial breast cancer: analysis of a series stratified by tumour characteristics, BRCA mutations and oophorectomy. Int J Cancer. 2002;101:555–9.

    PubMed  Article  CAS  Google Scholar 

  4. Antoniou A, Pharoah PD, Narod S, et al. 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. 2003;72:1117–30.

    PubMed  Article  CAS  Google Scholar 

  5. Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol. 2007;25:1329–33.

    PubMed  Article  Google Scholar 

  6. • Kurian AW, Sigal BM, Plevritis SK. Survival analysis of cancer risk reduction strategies for BRCA1/2 mutation carriers. J Clin Oncol. 2010;28:222–31. This study used decision analysis to simulate risk-reducing strategies in BRCA1 and BRCA2 mutation carriers to examine the effect of various strategies on survival.

    PubMed  Article  CAS  Google Scholar 

  7. Kriege M, Brekelmans CT, Boetes C, et al. Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med. 2004;351:427–37.

    PubMed  Article  CAS  Google Scholar 

  8. Saslow D, Boetes C, Burke W, et al. American Cancer Society guidelines for breast screening with MRI as an adjunct to mammography. CA Cancer J Clin. 2007;57:75–89.

    PubMed  Article  Google Scholar 

  9. Kuhl C, Weigel S, Schrading S, et al. Prospective multicenter cohort study to refine management recommendations for women at elevated familial risk of breast cancer: the EVA trial. J Clin Oncol. 2010;28:1450–7.

    PubMed  Article  Google Scholar 

  10. van der Velde NM, Mourits MJ, Arts HJ, et al. Time to stop ovarian cancer screening in BRCA1/2 mutation carriers? Int J Cancer. 2009;124:919–23.

    PubMed  Article  Google Scholar 

  11. Daly MB, Axilbund JE, Buys S, et al. Genetic/familial high-risk assessment: breast and ovarian. J Natl Compr Cancer Netw. 2010;8:562–94.

    CAS  Google Scholar 

  12. Narod SA, Dube MP, Klijn J, et al. Oral contraceptives and the risk of breast cancer in BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst. 2002;94:1773–9.

    PubMed  Article  CAS  Google Scholar 

  13. Whittemore AS, Balise RR, Pharoah PD, et al. Oral contraceptive use and ovarian cancer risk among carriers of BRCA1 or BRCA2 mutations. Br J Cancer. 2004;91:1911–5.

    PubMed  Article  CAS  Google Scholar 

  14. Cibula D, Zikan M, Dusek L, Majek O. Oral contraceptives and risk of ovarian and breast cancers in BRCA mutation carriers: a meta-analysis. Expert Rev Anticancer Ther. 2011;11:1197–207.

    PubMed  Article  CAS  Google Scholar 

  15. King MC, Wieand S, Hale K, et al. Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. JAMA. 2001;286:2251–6.

    PubMed  Article  CAS  Google Scholar 

  16. Narod SA, Brunet JS, Ghadirian P, et al. Tamoxifen and risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers: a case-control study. Hereditary Breast Cancer Clinical Study Group. Lancet. 2000;356:1876–81.

    PubMed  Article  CAS  Google Scholar 

  17. Gronwald J, Tung N, Foulkes WD, et al. Tamoxifen and contralateral breast cancer in BRCA1 and BRCA2 carriers: an update. Int J Cancer. 2006;118:2281–4.

    PubMed  Article  CAS  Google Scholar 

  18. Pierce LJ, Levin AM, Rebbeck TR, et al. Ten-year multi-institutional results of breast-conserving surgery and radiotherapy in BRCA1/2-associated stage I/II breast cancer. J Clin Oncol. 2006;24:2437–43.

    PubMed  Article  Google Scholar 

  19. Hartmann LC, Sellers TA, Schaid DJ, et al. Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. J Natl Cancer Inst. 2001;93:1633–7.

    PubMed  Article  CAS  Google Scholar 

  20. Meijers-Heijboer H, van Geel B, van Putten WL, et al. Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med. 2001;345:159–64.

    PubMed  Article  CAS  Google Scholar 

  21. Rebbeck TR, Friebel T, Lynch HT, et al. Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol. 2004;22:1055–62.

    PubMed  Article  Google Scholar 

  22. Kaas R, Verhoef S, Wesseling J, et al. Prophylactic mastectomy in BRCA1 and BRCA2 mutation carriers: very low risk for subsequent breast cancer. Ann Surg. 2010;251:488–92.

    PubMed  Article  Google Scholar 

  23. Heemskerk-Gerritsen BA, Brekelmans CT, Menke-Pluymers MB, et al. Prophylactic mastectomy in BRCA1/2 mutation carriers and women at risk of hereditary breast cancer: long-term experiences at the Rotterdam Family Cancer Clinic. Ann Surg Oncol. 2007;14:3335–44.

    PubMed  Article  Google Scholar 

  24. • Domchek SM, Friebel TM, Singer CF, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA. 2010;304:967–75. This is a prospective multicenter cohort study of BRCA1 and BRCA2 mutation carriers that demonstrated an association of RRSO and an improvement in overall survial.

    PubMed  Article  CAS  Google Scholar 

  25. Kauff ND, Brogi E, Scheuer L, et al. Epithelial lesions in prophylactic mastectomy specimens from women with BRCA mutations. Cancer. 2003;97:1601–8.

    PubMed  Article  Google Scholar 

  26. Isern AE, Loman N, Malina J, et al. Histopathological findings and follow-up after prophylactic mastectomy and immediate breast reconstruction in 100 women from families with hereditary breast cancer. Eur J Surg Oncol. 2008;34:1148–54.

    PubMed  Article  CAS  Google Scholar 

  27. Van Geel AN, Contant CM, Wai RT, et al. Mastectomy by inverted drip incision and immediate reconstruction: data from 510 cases. Ann Surg Oncol. 2003;10:389–95.

    PubMed  Article  Google Scholar 

  28. Zion SM, Slezak JM, Sellers TA, et al. Reoperations after prophylactic mastectomy with or without implant reconstruction. Cancer. 2003;98:2152–60.

    PubMed  Article  Google Scholar 

  29. Barton MB, West CN, Liu IL, et al. Complications following bilateral prophylactic mastectomy. J Natl Cancer Inst Monogr. 2005;35:61–6.

    PubMed  Article  Google Scholar 

  30. Lostumbo L, Carbine N, Wallace J, Ezzo J. Prophylactic mastectomy for the prevention of breast cancer. Cochrane Database Syst Rev. 2004 :CD002748.

  31. Friebel TM, Domchek SM, Neuhausen SL, et al. Bilateral prophylactic oophorectomy and bilateral prophylactic mastectomy in a prospective cohort of unaffected BRCA1 and BRCA2 mutation carriers. Clin Breast Cancer. 2007;7:875–82.

    PubMed  Article  Google Scholar 

  32. Landsbergen KM, Prins JB, Kamm YJ, et al. Female BRCA mutation carriers with a preference for prophylactic mastectomy are more likely to participate an educational-support group and to proceed with the preferred intervention within 2 years. Fam Cancer. 2010;9:213–20.

    PubMed  Article  Google Scholar 

  33. Skytte AB, Gerdes AM, Andersen MK, et al. Risk-reducing mastectomy and salpingo-oophorectomy in unaffected BRCA mutation carriers: uptake and timing. Clin Genet. 2010;77:342–9.

    PubMed  Article  CAS  Google Scholar 

  34. Metcalfe K, Lynch HT, Ghadirian P, et al. Contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2004;22:2328–35.

    PubMed  Article  CAS  Google Scholar 

  35. Graeser MK, Engel C, Rhiem K, et al. Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2009;27:5887–92.

    PubMed  Article  Google Scholar 

  36. Malone KE, Begg CB, Haile RW, et al. Population-based study of the risk of second primary contralateral breast cancer associated with carrying a mutation in BRCA1 or BRCA2. J Clin Oncol. 2010;28:2404–10.

    PubMed  Article  CAS  Google Scholar 

  37. • Metcalfe K, Gershman S, Lynch HT, et al. Predictors of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers. Br J Cancer. 2011;104:1384–92. This is a prospective trial following BRCA1 and BRCA2 carriers to estimate the risk of contralateral breast cancer and the factors that influence this risk.

    PubMed  Article  CAS  Google Scholar 

  38. Pierce LJ, Phillips KA, Griffith KA, et al. Local therapy in BRCA1 and BRCA2 mutation carriers with operable breast cancer: comparison of breast conservation and mastectomy. Breast Cancer Res Treat. 2010;121:389–98.

    PubMed  Article  Google Scholar 

  39. Kiely BE, Jenkins MA, McKinley JM, et al. Contralateral risk-reducing mastectomy in BRCA1 and BRCA2 mutation carriers and other high-risk women in the Kathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer (kConFab). Breast Cancer Res Treat. 2010;120:715–23.

    PubMed  Article  CAS  Google Scholar 

  40. van Sprundel TC, Schmidt MK, Rookus MA, et al. Risk reduction of contralateral breast cancer and survival after contralateral prophylactic mastectomy in BRCA1 or BRCA2 mutation carriers. Br J Cancer. 2005;93:287–92.

    PubMed  Article  Google Scholar 

  41. Brandberg Y, Sandelin K, Erikson S, et al. Psychological reactions, quality of life, and body image after bilateral prophylactic mastectomy in women at high risk for breast cancer: a prospective 1-year follow-up study. J Clin Oncol. 2008;26:3943–9.

    PubMed  Article  Google Scholar 

  42. Zendejas B, Moriarty JP, O'Byrne J, et al. Cost-effectiveness of contralateral prophylactic mastectomy versus routine surveillance in patients with unilateral breast cancer. J Clin Oncol. 2011;29:2993–3000.

    PubMed  Article  Google Scholar 

  43. Brose MS, Rebbeck TR, Calzone KA, et al. Cancer risk estimates for BRCA1 mutation carriers identified in a risk evaluation program. J Natl Cancer Inst. 2002;94:1365–72.

    PubMed  Article  CAS  Google Scholar 

  44. Nathanson KL, Domchek SM. Therapeutic approaches for women predisposed to breast cancer. Annu Rev Med. 2011;62:295–306.

    PubMed  Article  CAS  Google Scholar 

  45. Kauff ND, Satagopan JM, Robson ME, et al. Risk-reducing salpingo-oophorectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med. 2002;346:1609–15.

    PubMed  Article  Google Scholar 

  46. Rebbeck TR, Lynch HT, Neuhausen SL, et al. Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med. 2002;346:1616–22.

    PubMed  Article  Google Scholar 

  47. Rutter JL, Wacholder S, Chetrit A, et al. 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. 2003;95:1072–8.

    PubMed  Article  Google Scholar 

  48. Domchek SM, Friebel TM, Neuhausen SL, et al. Mortality after bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers: a prospective cohort study. Lancet Oncol. 2006;7:223–9.

    PubMed  Article  CAS  Google Scholar 

  49. Finch A, Beiner M, Lubinski J, et al. Salpingo-oophorectomy and the risk of ovarian, fallopian tube, and peritoneal cancers in women with a BRCA1 or BRCA2 Mutation. JAMA. 2006;296:185–92.

    PubMed  Article  CAS  Google Scholar 

  50. 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;26:1331–7.

    PubMed  Article  Google Scholar 

  51. • Rebbeck TR, Kauff ND, Domchek SM. Meta-analysis of risk reduction estimates associated with risk-reducing salpingo-oophorectomy in BRCA1 or BRCA2 mutation carriers. J Natl Cancer Inst. 2009;101:80–7. This is a meta-analysis of 10 studies that examined breast or gynecologic cancer outcomes in BRCA1 and BRCA2 mutation carriers who had undergone RRSO.

    PubMed  Article  CAS  Google Scholar 

  52. Casey MJ, Synder C, Bewtra C, et al. Intra-abdominal carcinomatosis after prophylactic oophorectomy in women of hereditary breast ovarian cancer syndrome kindreds associated with BRCA1 and BRCA2 mutations. Gynecol Oncol. 2005;97:457–67.

    PubMed  Article  Google Scholar 

  53. Powell CB, Chen LM, McLennan J, et al. Risk-reducing salpingo-oophorectomy (RRSO) in BRCA mutation carriers: experience with a consecutive series of 111 patients using a standardized surgical-pathological protocol. Int J Gynecol Cancer. 2011;21:846–51.

    PubMed  Article  Google Scholar 

  54. Manchanda R, Abdelraheim A, Johnson M, et al. Outcome of risk-reducing salpingo-oophorectomy in BRCA carriers and women of unknown mutation status. BJOG. 2011;118:814–24.

    PubMed  Article  CAS  Google Scholar 

  55. Domchek SM, Friebel TM, Garber JE, et al. Occult ovarian cancers identified at risk-reducing salpingo-oophorectomy in a prospective cohort of BRCA1/2 mutation carriers. Breast Cancer Res Treat. 2010;124:195–203.

    PubMed  Article  Google Scholar 

  56. Crum CP, Drapkin R, Miron A, et al. The distal fallopian tube: a new model for pelvic serous carcinogenesis. Curr Opin Obstet Gynecol. 2007;19:3–9.

    PubMed  Article  Google Scholar 

  57. Kurman RJ, Shih Ie M. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol. 2010;34:433–43.

    PubMed  Article  Google Scholar 

  58. Cibula D, Widschwendter M, Majek O, Dusek L. Tubal ligation and the risk of ovarian cancer: review and meta-analysis. Hum Reprod Update. 2011;17:55–67.

    PubMed  Article  CAS  Google Scholar 

  59. Greene MH, Mai PL, Schwartz PE. Does bilateral salpingectomy with ovarian retention warrant consideration as a temporary bridge to risk-reducing bilateral oophorectomy in BRCA1/2 mutation carriers? Am J Obstet Gynecol. 2011;204:19 e11–6.

    Article  Google Scholar 

  60. Collins IM, Domchek SM, Huntsman DG, Mitchell G. The tubal hypothesis of ovarian cancer: caution needed. Lancet Oncol. 2011;12:1089–91.

    PubMed  Article  Google Scholar 

  61. Eisen A, Lubinski J, Klijn J, et al. Breast cancer risk following bilateral oophorectomy in BRCA1 and BRCA2 mutation carriers: an international case-control study. J Clin Oncol. 2005;23:7491–6.

    PubMed  Article  Google Scholar 

  62. Kramer JL, Velazquez IA, Chen BE, et al. Prophylactic oophorectomy reduces breast cancer penetrance during prospective, long-term follow-up of BRCA1 mutation carriers. J Clin Oncol. 2005;23:8629–35.

    PubMed  Article  Google Scholar 

  63. Shah P, Rosen M, Stopfer J, et al. Prospective study of breast MRI in BRCA1 and BRCA2 mutation carriers: effect of mutation status on cancer incidence. Breast Cancer Res Treat. 2009;118:539–46.

    PubMed  Article  CAS  Google Scholar 

  64. Fakkert IE, Jansen L, Meijer K, et al. Breast cancer screening in BRCA1 and BRCA2 mutation carriers after risk reducing salpingo-oophorectomy. Breast Cancer Res Treat. 2011;129:157–64.

    PubMed  Article  Google Scholar 

  65. Kenkhuis MJ, de Bock GH, Elferink PO, et al. Short-term surgical outcome and safety of risk reducing salpingo-oophorectomy in BRCA1/2 mutation carriers. Maturitas. 2010;66:310–4.

    PubMed  Article  CAS  Google Scholar 

  66. Madalinska JB, van Beurden M, Bleiker EM, et al. The impact of hormone replacement therapy on menopausal symptoms in younger high-risk women after prophylactic salpingo-oophorectomy. J Clin Oncol. 2006;24:3576–82.

    PubMed  Article  Google Scholar 

  67. Finch A, Metcalfe KA, Chiang JK, et al. The impact of prophylactic salpingo-oophorectomy on menopausal symptoms and sexual function in women who carry a BRCA mutation. Gynecol Oncol. 2011;121:163–8.

    PubMed  Article  CAS  Google Scholar 

  68. Rocca WA, Grossardt BR, de Andrade M, et al. Survival patterns after oophorectomy in premenopausal women: a population-based cohort study. Lancet Oncol. 2006;7:821–8.

    PubMed  Article  Google Scholar 

  69. Parker WH, Broder MS, Chang E, et al. Ovarian conservation at the time of hysterectomy and long-term health outcomes in the nurses' health study. Obstet Gynecol. 2009;113:1027–37.

    PubMed  Google Scholar 

  70. Cohen JV, Chiel L, Boghossian L, et al. Non-cancer endpoints in BRCA1/2 carriers after risk-reducing salpingo-oophorectomy. Fam Cancer. 2012;11:69–75.

    PubMed  Article  CAS  Google Scholar 

  71. Rebbeck TR, Friebel T, Wagner T, et al. Effect of short-term hormone replacement therapy on breast cancer risk reduction after bilateral prophylactic oophorectomy in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol. 2005;23:7804–10.

    PubMed  Article  CAS  Google Scholar 

  72. Domchek S, Friebel T, Neuhausen S, et al. Is hormone replacement therapy (HRT) following risk-reducing salpingo-oophorectomy (RRSO) in BRCA1 (B1)- and BRCA2 (B2)-mutation carriers associated with an increased risk of breast cancer? J Clin Oncol. 2011;29(Suppl):1501.

    Google Scholar 

  73. Eisen A, Lubinski J, Gronwald J, et al. Hormone therapy and the risk of breast cancer in BRCA1 mutation carriers. J Natl Cancer Inst. 2008;100:1361–7.

    PubMed  Article  CAS  Google Scholar 

  74. Gabriel CA, Tigges-Cardwell J, Stopfer J, et al. Use of total abdominal hysterectomy and hormone replacement therapy in BRCA1 and BRCA2 mutation carriers undergoing risk-reducing salpingo-oophorectomy. Fam Cancer. 2009;8:23–8.

    PubMed  Article  CAS  Google Scholar 

  75. Anderson GL, Chlebowski RT, Aragaki AK, et al. Conjugated equine oestrogen and breast cancer incidence and mortality in postmenopausal women with hysterectomy: extended follow-up of the Women's Health Initiative randomised placebo-controlled trial. Lancet Oncol. 2012.Epub ahead of print.

  76. Finch A, Metcalfe KA, Chiang J, et al. The impact of prophylactic salpingo-oophorectomy on quality of life and psychological distress in women with a BRCA mutation. Psychooncology. 2011. Epub ahead of print.

  77. Campfield Bonadies D, Moyer A, Matloff ET. What I wish I'd known before surgery: BRCA carriers' perspectives after bilateral salipingo-oophorectomy. Fam Cancer. 2011;10:79–85.

    PubMed  Article  Google Scholar 

  78. Rhiem K, Foth D, Wappenschmidt B, et al. Risk-reducing salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers. Arch Gynecol Obstet. 2011;283:623–7.

    PubMed  Article  Google Scholar 

  79. Bradbury AR, Ibe CN, Dignam JJ, et al. Uptake and timing of bilateral prophylactic salpingo-oophorectomy among BRCA1 and BRCA2 mutation carriers. Genet Med. 2008;10:161–6.

    PubMed  Article  Google Scholar 

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Maxwell, K.N., Domchek, S.M. Prophylactic Mastectomy and Risk-Reducing Salpingo-oophorectomy in BRCA1/2 Mutation Carriers. Curr Breast Cancer Rep 4, 199–206 (2012). https://doi.org/10.1007/s12609-012-0086-4

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Keywords

  • BRCA1
  • BRCA2
  • Salpingo-oophorectomy
  • Mastectomy
  • Risk reduction
  • Breast cancer
  • Ovarian cancer