Skip to main content

Advertisement

SpringerLink
Log in

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

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

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.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  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) vi31-34

  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 13:51–56

    Article  Google Scholar 

  3. Chen S, Parmigiani G (2007) Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol 25:1329–1333

    Article  PubMed Central  PubMed  Google Scholar 

  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 199:680–683

    Article  PubMed  Google Scholar 

  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 7:223–229

    Article  CAS  PubMed  Google Scholar 

  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 304:967–975

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Domchek SM, Stopfer JE, Rebbeck TR (2006) Bilateral risk-reducing oophorectomy in BRCA1 and BRCA2 mutation carriers. J Natl Compr Cancer Netw 4:177–182

    Google Scholar 

  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 32:1547–1553

    Article  PubMed  Google Scholar 

  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 7:875–882

    Article  PubMed  Google Scholar 

  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):428–433

    Article  PubMed  Google Scholar 

  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 113:957–966

  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 26:1331–1337

    Article  PubMed Central  PubMed  Google Scholar 

  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 346:1609–1615

    Article  PubMed  Google Scholar 

  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):96–103

    Article  PubMed  Google Scholar 

  15. Menon U, Griffin M, Gentry-Maharaj A (2014) Ovarian cancer screening—current status, future directions. Gynecol Oncol 132:490–495

    Article  PubMed Central  PubMed  Google Scholar 

  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 122:2017–2022

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  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 4:97–103

    Article  PubMed  Google Scholar 

  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. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#detection

  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 13:148–154

    Article  PubMed Central  PubMed  Google Scholar 

  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 346:1616–1622

    Article  PubMed  Google Scholar 

  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 283:623–627

    Article  PubMed  Google Scholar 

  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 118:510–517

    Article  PubMed Central  PubMed  Google Scholar 

  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 8:277–87

  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 19:44–54

  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 96:718–24

  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 25:301–7

  27. Mahon SM (2001) Factors affecting genetic testing and decisions about prophylactic surgery. Clin J Oncol Nur 5:117–20

  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 91:1787–94

  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 16:5094–106

Download references

Acknowledgments

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

None.

Author information

Authors and Affiliations

  1. Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, The University of Pennsylvania School of Medicine, 2 Blockley Hall, 423 Guardian Drive, Philadelphia, PA, 19104-6021, USA

    Xinglei Chai, Tara M. Friebel, Jinbo Chen & Timothy R. Rebbeck

  2. Basser Center for BRCA and Abramson Cancer Center, The University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Tara M. Friebel, Susan M. Domchek & Timothy R. Rebbeck

  3. Department of Medicine, The University of Pennsylvania School of Medicine, Philadelphia, PA, USA

    Susan M. Domchek

  4. Division of Special Gynecology, Medical University of Vienna, Vienna, Austria

    Christian F. Singer

  5. Department of Genomic Medicine, MAHSC, St. Mary’s Hospital, University of Manchester, Manchester, UK

    D. Gareth Evans

  6. Creighton University, Omaha, NE, USA

    Henry T. Lynch

  7. Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA

    Claudine Isaacs

  8. Dana Farber Cancer Institute, Boston, MA, USA

    Judy E. Garber

  9. Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, CA, USA

    Susan L. Neuhausen

  10. Yale University, New Haven, CT, USA

    Ellen Matloff

  11. The Institute of Cancer Research & Royal Marsden NHS Foundation Trust, London, UK

    Rosalind Eeles

  12. The Institute of Cancer Research & Royal Marsden NHS Foundation Trust, Sutton, UK

    Rosalind Eeles

  13. Beth Israel Deaconess Medical Center, Boston, MA, USA

    Nadine Tung

  14. City of Hope National Medical Center, Duarte, CA, USA

    Jeffrey N. Weitzel

  15. Mayo Clinic College of Medicine, Rochester, MN, USA

    Fergus J. Couch

  16. NorthShore University HealthSystem, Evanston, IL, USA

    Peter J. Hulick

  17. The University of Chicago, Chicago, IL, USA

    Peter J. Hulick

  18. Jonsson Comprehensive Cancer Center at the University of California, Los Angeles, CA, USA

    Patricia A. Ganz

  19. Fox Chase Cancer Center, Philadelphia, PA, USA

    Mary B. Daly

  20. University of Chicago Medical Center, Chicago, IL, USA

    Olufunmilayo I. Olopade

  21. Southwestern Medical Center, University of Texas, Dallas, TX, USA

    Gail Tomlinson

  22. Baylor-Charles A. Sammons Cancer Center, Dallas, TX, USA

    Joanne L. Blum

Authors
  1. Xinglei Chai
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tara M. Friebel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christian F. Singer
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. D. Gareth Evans
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Henry T. Lynch
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Claudine Isaacs
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Judy E. Garber
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Susan L. Neuhausen
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ellen Matloff
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Rosalind Eeles
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Nadine Tung
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Jeffrey N. Weitzel
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Fergus J. Couch
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Peter J. Hulick
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Patricia A. Ganz
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Mary B. Daly
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Olufunmilayo I. Olopade
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Gail Tomlinson
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Joanne L. Blum
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Susan M. Domchek
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Jinbo Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Timothy R. Rebbeck
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Jinbo Chen or Timothy R. Rebbeck.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 43 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chai, X., Friebel, T.M., Singer, C.F. et al. Use of risk-reducing surgeries in a prospective cohort of 1,499 BRCA1 and BRCA2 mutation carriers. Breast Cancer Res Treat 148, 397–406 (2014). https://doi.org/10.1007/s10549-014-3134-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-014-3134-0

Keywords

Search

Navigation