Breast Cancer Research and Treatment

, Volume 148, Issue 2, pp 397–406 | Cite as

Use of risk-reducing surgeries in a prospective cohort of 1,499 BRCA1 and BRCA2 mutation carriers

  • Xinglei Chai
  • Tara M. Friebel
  • Christian F. Singer
  • D. Gareth Evans
  • Henry T. Lynch
  • Claudine Isaacs
  • Judy E. Garber
  • Susan L. Neuhausen
  • Ellen Matloff
  • Rosalind Eeles
  • Nadine Tung
  • Jeffrey N. Weitzel
  • Fergus J. Couch
  • Peter J. Hulick
  • Patricia A. Ganz
  • Mary B. Daly
  • Olufunmilayo I. Olopade
  • Gail Tomlinson
  • Joanne L. Blum
  • Susan M. Domchek
  • Jinbo ChenEmail author
  • Timothy R. RebbeckEmail author


Inherited mutations in BRCA1 or BRCA2 (BRCA1/2) confer very high risk of breast and ovarian cancers. Genetic testing and counseling can reduce risk and death from these cancers if appropriate preventive strategies are applied, including risk-reducing salpingo-oophorectomy (RRSO) or risk-reducing mastectomy (RRM). However, some women who might benefit from these interventions do not take full advantage of them. We evaluated RRSO and RRM use in a prospective cohort of 1,499 women with inherited BRCA1/2 mutations from 20 centers who enrolled in the study without prior cancer or RRSO or RRM and were followed forward for the occurrence of these events. We estimated the age-specific usage of RRSO/RRM in this cohort using Kaplan–Meier analyses. Use of RRSO was 45 % for BRCA1 and 34 % for BRCA2 by age 40, and 86 % for BRCA1 and 71 % for BRCA2 by age 50. RRM usage was estimated to be 46 % by age 70 in both BRCA1 and BRCA2 carriers. BRCA1 mutation carriers underwent RRSO more frequently than BRCA2 mutation carriers overall, but the uptake of RRSO in BRCA2 was similar after mutation testing and in women born since 1960. RRM uptake was similar for both BRCA1 and BRCA2. Childbearing influenced the use of RRSO and RRM in both BRCA1 and BRCA2. Uptake of RRSO is high, but some women are still diagnosed with ovarian cancer before undergoing RRSO. This suggests that research is needed to understand the optimal timing of RRSO to maximize risk reduction and limit potential adverse consequences of RRSO.


Risk reduction BRCA1 BRCA2 Surgical prevention Uptake 



The PROSE Consortium acknowledges the following centers and individuals who contributed to the present study: University of Vienna, Austria (Christian Singer); Beth Israel, Boston, MA (Nadine Tung); Baylor-Charles A. Sammons Cancer Center (Joanne L. Blum, Becky Althaus, Gabrielle Ethington, Estelle Brothers); City of Hope, Duarte, CA (Jeffrey Weitzel); Creighton University, Omaha, NE (Carrie Snyder, Henry T. Lynch, Patrice Watson); Dana-Farber Cancer Institute, Boston, MA (Katherine Corso, Kathryn Stoeckert, Judy E. Garber); NorthShore University HealthSystem, Evanston, IL (Peter J. Hulick, Christina Selkirk, Scott M. Weissman); Fox Chase Cancer Center, Philadelphia, PA (Mary B. Daly); Guy’s Hospital and St. Thomas Foundation Trust, London, UK (Gabriella Pichert, Caroline Langman, Leena da Silva); Georgetown University, Washington, DC (Camille Jasper, Claudine Isaacs); University of California, Los Angeles (Patricia A. Ganz, Joyce L. Seldon); Mayo Clinic College of Medicine, Rochester, MN (Fergus Couch); Netherlands Cancer Institute, Amsterdam, Netherlands (Marc van Beurden, Laura van ‘t Veer); The Institute of Cancer Research & Royal Marsden NHS Foundation Trust, London & Sutton (Rosalind Eeles, Elizabeth Bancroft, Elizabeth Page, Lucia D’Mello, Susan Shanley, Audrey Ardern-Jones, Elena Castro, Anita Mitra, Kelly Kohut, Jennifer Wiggins, The Carrier Clinic Collaborators); St. Mary’s Hospital, Manchester, UK (Gareth Evans, Fiona Lalloo); University of Texas-Southwestern, Dallas (n = 63, Gail Tomlinson); University of Chicago, Chicago, IL (Shelly Cummings, Olufunmilayo Olopade); University of Pennsylvania, Philadelphia, PA (Susan Domchek, Tara M Friebel, Timothy Rebbeck, Jill Stopfer, Jacquelyn Powers, Katherine Nathanson); University of Utah, Salt Lake City, UT and University of California, Irvine (Susan Neuhausen, Linda Steele); Women’s College Hospital, Toronto, CA (Steven A. Narod); Yale University, New Haven, CT (Ellen T. Matloff, Karina L. Brierly). This study was supported by grants from the Public Health Service (R01-CA164305 to XLC and JBC, R01-CA83855 and R01-CA102776 to TRR), The Basser Center for BRCA at the University of Pennsylvania (to TRR, SMD), Komen Foundation for the Cure (SMD), the Dana-Farber/Harvard Cancer Center SPORE in BC P50 CA-089393 (to JEG), the Department of Defense (DAMD-17-96-I-6088 to AKG; DAMD-17-94-J-4340 and DAMD-17-97-I-7112 to HTL), P30-CA51008-15 (to Georgetown University), The Utah Cancer registry (funded by Public Health Service Grant NO1-CN-6700) and the Utah State Department of Health, the Nebraska State Cancer and Smoking-Related Diseases Research Program (LB595 to HTL), P30-CA-16042 (to PAG), Cancer Research UK Grant Number C5047/A7357 (to RE), and NCI P30 CA51008-12 (to CI). OIO is Doris Duke Distinguished Clinical Scientist. RE acknowledges The Support of the NIHR to The Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under grant number RC4CA153828 (PI: J. Weitzel). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Conflict of interest


Supplementary material

10549_2014_3134_MOESM1_ESM.docx (43 kb)
Supplementary material 1 (DOCX 43 kb)


  1. 1.
    J. Balmaña, O. Díez, I.T. Rubio, F. Cardoso, E.G.W. Group, BRCA in breast cancer: ESMO Clinical Practice Guidelines, Ann Oncol 22 Suppl 6 (2011) vi31-34Google Scholar
  2. 2.
    Beattie MS, Crawford B, Lin F, Vittinghoff E, Ziegler J (2009) Uptake, time course, and predictors of risk-reducing surgeries in BRCA carriers. Genet Test Mol Biomark 13:51–56CrossRefGoogle Scholar
  3. 3.
    Chen S, Parmigiani G (2007) Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 25:1329–1333PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Collins IM, Milne RL, Weideman PC, McLachlan SA, Friedlander ML, Hopper JL, Phillips KA, K.C.F.C.F.R.I.F.B. Cancer (2013) Preventing breast and ovarian cancers in high-risk BRCA1 and BRCA2 mutation carriers. Med J Aust 199:680–683PubMedCrossRefGoogle Scholar
  5. 5.
    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 7:223–229PubMedCrossRefGoogle Scholar
  6. 6.
    Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, Isaacs C, Garber JE, Neuhausen SL, Matloff E, Eeles R, Pichert G, Van t’veer L, Tung N, Weitzel JN, Couch FJ, Rubinstein WS, Ganz PA, Daly MB, Olopade OI, Tomlinson G, Schildkraut J, Blum JL, Rebbeck TR (2010) Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA 304:967–975PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Domchek SM, Stopfer JE, Rebbeck TR (2006) Bilateral risk-reducing oophorectomy in BRCA1 and BRCA2 mutation carriers. J Natl Compr Cancer Netw 4:177–182Google Scholar
  8. 8.
    Finch AP, Lubinski J, Møller P, Singer CF, Karlan B, Senter L, Rosen B, Maehle L, Ghadirian P, Cybulski C, Huzarski T, Eisen A, Foulkes WD, Kim-Sing C, Ainsworth P, Tung N, Lynch HT, Neuhausen S, Metcalfe KA, Thompson I, Murphy J, Sun P, Narod SA (2014) Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation. J Clin Oncol 32:1547–1553PubMedCrossRefGoogle Scholar
  9. 9.
    Friebel TM, Domchek SM, Neuhausen SL, Wagner T, Evans DG, Isaacs C, Garber JE, Daly MB, Eeles R, Matloff E, Tomlinson G, Lynch HT, Tung N, Blum JL, Weitzel J, Rubinstein WS, Ganz PA, Couch F, Rebbeck TR (2007) Bilateral prophylactic oophorectomy and bilateral prophylactic mastectomy in a prospective cohort of unaffected BRCA1 and BRCA2 mutation carriers. Clin Breast Cancer 7:875–882PubMedCrossRefGoogle Scholar
  10. 10.
    Garcia C, Wendt J, Lyon L, Jones J, Littell RD, Armstrong MA, Raine-Bennett T, Powell CB (2013) Risk management options elected by women after testing positive for a BRCA mutation. Gynecol Oncol 132(2):428–433PubMedCrossRefGoogle Scholar
  11. 11.
    A.C.o.O.a. Gynecologists, A.C.o.P. Bulletins–Gynecology, A.C.o. Genetics, S.o.G. Oncologists (2009) ACOG Practice Bulletin No. 103: Hereditary breast and ovarian cancer syndrome. Obstet Gynecol 113:957–966Google Scholar
  12. 12.
    Kauff N, Domchek S, Friebel T, Robson M, Lee J, Garber J, Isaacs C, Evans G, Lynch H, Eeles R, Neuhausen S, Daly M, Matloff E, Blum J, Sabbatini P, Hudis C, Norton L, Barakat R, Offit K, Rebbeck T (2008) Risk-reducing salpingo-oophorectomy for the prevention of BRCA1 and BRCA2 associated breast and gynecologic cancer: a multi-center, prospective study. J Clin Oncol 26:1331–1337PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    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 346:1609–1615PubMedCrossRefGoogle Scholar
  14. 14.
    Mannis GN, Fehniger JE, Creasman JS, Jacoby VL, Beattie MS (2013) Risk-reducing salpingo-oophorectomy and ovarian cancer screening in 1077 women after BRCA testing. JAMA Intern Med 173(2013):96–103PubMedCrossRefGoogle Scholar
  15. 15.
    Menon U, Griffin M, Gentry-Maharaj A (2014) Ovarian cancer screening—current status, future directions. Gynecol Oncol 132:490–495PubMedCentralPubMedCrossRefGoogle Scholar
  16. 16.
    Metcalfe KA, Birenbaum-Carmeli D, Lubinski J, Gronwald J, Lynch H, Moller P, Ghadirian P, Foulkes WD, Klijn J, Friedman E, Kim-Sing C, Ainsworth P, Rosen B, Domchek S, Wagner T, Tung N, Manoukian S, Couch F, Sun P, Narod SA (2008) International variation in rates of uptake of preventive options in BRCA1 and BRCA2 mutation carriers. Int J Cancer 122:2017–2022PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    Metcalfe KA, Snyder C, Seidel J, Hanna D, Lynch HT, Narod S (2005) The use of preventive measures among healthy women who carry a BRCA1 or BRCA2 mutation. Fam Cancer 4:97–103PubMedCrossRefGoogle Scholar
  18. 18.
    NCCN, NCCN guidelines for detection, prevention, and risk reduction: genetic/familial high risk assessment: breast and ovarian (v 2.2013). Cancer guidelines <span data-locatortype=“url”>, 2013.
  19. 19.
    Plon SE, Cooper HP, Parks B, Dhar SU, Kelly PA, Weinberg AD, Staggs S, Wang T, Hilsenbeck S (2011) Genetic testing and cancer risk management recommendations by physicians for at-risk relatives. Genet Med 13:148–154PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Rebbeck TR, Lynch HT, Neuhausen SL, Narod SA, Van’t Veer L, Garber JE, Evans E, Isaacs C, Daly MB, Matloff E, Olopade OI, Weber BL (2002) Prophylactic oophorectomy in carriers of BRCA1 or BRCA2 mutations. N Engl J Med 346:1616–1622PubMedCrossRefGoogle Scholar
  21. 21.
    Rhiem K, Foth D, Wappenschmidt B, Gevensleben H, Büttner R, Ulrich U, Schmutzler RK (2011) Risk-reducing salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers. Arch Gynecol Obstet 283:623–627PubMedCrossRefGoogle Scholar
  22. 22.
    Schwartz MD, Isaacs C, Graves KD, Poggi E, Peshkin BN, Gell C, Finch C, Kelly S, Taylor KL, Perley L (2012) Long-term outcomes of BRCA1/BRCA2 testing: risk reduction and surveillance. Cancer 118:510–517PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    Morgan D, Sylvester H, Lucas FL et al (2009) Cancer prevention and screening practices among women at risk for hereditary breast and ovarian cancer after genetic counseling in the community setting. Fam Cancer 8:277–87Google Scholar
  24. 24.
    Morgan D, Sylvester H, Lucas FL et al (2010) Perceptions of high-risk care and barriers to care among women at risk for hereditary breast and ovarian cancer following genetic counseling in the community setting. J Genet Couns 19:44–54Google Scholar
  25. 25.
    Foster C, Watson M, Eeles R et al (2007) Predictive genetic testing for BRCA1/2 in a UK clinical cohort: three year follow-up. Br J Cancer 96:718–24Google Scholar
  26. 26.
    Madalinska JB, van Beurden M, Bleiker EM et al (2007) Predictors of prophylactic bilateral salpingo-oophorectomy compared with gynecologic screening use in BRCA1/2 mutation carriers. J Clin Oncol 25:301–7Google Scholar
  27. 27.
    Mahon SM (2001) Factors affecting genetic testing and decisions about prophylactic surgery. Clin J Oncol Nur 5:117–20Google Scholar
  28. 28.
    Watson M, Foster C, Eeles R et al (2004) Psychosocial impact of breast/ovarian (BRCA1/2) cancer predictive genetic testing in a UK multi-centre clinical cohort. Br J Cancer 91:1787–94Google Scholar
  29. 29.
    Miller SM, Roussi P, Daly MB et al (2010) New strategies in ovarian cancer: uptake and experience of women at high risk of ovarian cancer who are considering risk-reducing salpingo-oophorectomy. Clin Cancer Res 16:5094–106Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Xinglei Chai
    • 1
  • Tara M. Friebel
    • 1
    • 2
  • Christian F. Singer
    • 4
  • D. Gareth Evans
    • 5
  • Henry T. Lynch
    • 6
  • Claudine Isaacs
    • 7
  • Judy E. Garber
    • 8
  • Susan L. Neuhausen
    • 9
  • Ellen Matloff
    • 10
  • Rosalind Eeles
    • 11
    • 12
  • Nadine Tung
    • 13
  • Jeffrey N. Weitzel
    • 14
  • Fergus J. Couch
    • 15
  • Peter J. Hulick
    • 16
    • 17
  • Patricia A. Ganz
    • 18
  • Mary B. Daly
    • 19
  • Olufunmilayo I. Olopade
    • 20
  • Gail Tomlinson
    • 21
  • Joanne L. Blum
    • 22
  • Susan M. Domchek
    • 2
    • 3
  • Jinbo Chen
    • 1
    Email author
  • Timothy R. Rebbeck
    • 1
    • 2
    Email author
  1. 1.Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and BiostatisticsThe University of Pennsylvania School of MedicinePhiladelphiaUSA
  2. 2.Basser Center for BRCA and Abramson Cancer CenterThe University of Pennsylvania School of MedicinePhiladelphiaUSA
  3. 3.Department of MedicineThe University of Pennsylvania School of MedicinePhiladelphiaUSA
  4. 4.Division of Special GynecologyMedical University of ViennaViennaAustria
  5. 5.Department of Genomic Medicine, MAHSC, St. Mary’s HospitalUniversity of ManchesterManchesterUK
  6. 6.Creighton UniversityOmahaUSA
  7. 7.Lombardi Comprehensive Cancer CenterGeorgetown UniversityWashingtonUSA
  8. 8.Dana Farber Cancer InstituteBostonUSA
  9. 9.Department of Population SciencesBeckman Research Institute of City of HopeDuarteUSA
  10. 10.Yale UniversityNew HavenUSA
  11. 11.The Institute of Cancer Research & Royal Marsden NHS Foundation TrustLondonUK
  12. 12.The Institute of Cancer Research & Royal Marsden NHS Foundation TrustSuttonUK
  13. 13.Beth Israel Deaconess Medical CenterBostonUSA
  14. 14.City of Hope National Medical CenterDuarteUSA
  15. 15.Mayo Clinic College of MedicineRochesterUSA
  16. 16.NorthShore University HealthSystemEvanstonUSA
  17. 17.The University of ChicagoChicagoUSA
  18. 18.Jonsson Comprehensive Cancer Center at the University of CaliforniaLos AngelesUSA
  19. 19.Fox Chase Cancer CenterPhiladelphiaUSA
  20. 20.University of Chicago Medical CenterChicagoUSA
  21. 21.Southwestern Medical CenterUniversity of TexasDallasUSA
  22. 22.Baylor-Charles A. Sammons Cancer CenterDallasUSA

Personalised recommendations