Salpingo-oophorectomy and the Risk of Ovarian, Fallopian Tube, and Peritoneal Cancers in Women With a BRCA1 or BRCA2 Mutation

Finch, Amy MS
Beiner, Mario MD
Lubinski, Jan MD, PhD
Lynch, Henry T. MD
Moller, Pal MD
Rosen, Barry MD
Murphy, Joan MD
Ghadirian, Parviz PhD
Friedman, Eitan MD
Foulkes, William D. MD
Kim-Sing, Charmaine MD
Wagner, Teresa MD
Tung, Nadine MD
Couch, Fergus PhD
Stoppa-Lyonnet, Dominique MD
Ainsworth, Peter MD
Daly, Mary MD
Pasini, Babara MD
Gershoni-Baruch, Ruth MD
Eng, Charis MD
Olopade, Olufunmilayo I. MD
McLennan, Jane MD
Karlan, Beth MD
Weitzel, Jeffrey MD
Sun, Ping PhD
Narod, Steven A. MD

Centre for Research in Women's Health, Toronto-Sunnybrook Regional Cancer Center, Toronto, Ontario (Ms Finch, Drs Beiner, Sun, and Narod); Pomeranian Medical University, Szczecin, Poland (Dr Lubinski); Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Neb (Dr Lynch); Norwegian Radium Hospital, Oslo, Norway (Dr Moller); Department of Gynecology Oncology, University Health Network, University of Toronto (Drs Rosen and Murphy); Department of Cancer Genetics, Departments of Medicine and Genetics, Epidemiology Research Unit, CHUM Hôtel-Dieu, University of Montreal, Montreal, Quebec (Dr Ghadirian); Chaim Sheba Medical Center, Tel Hashomer, Israel (Dr Friedman); Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montréal, Quebec (Dr Foulkes); BC Cancer Agency, Vancouver; British Columbia (Dr Kim-Sing); Division of Senology, Medical University of Vienna and Private Trust for Breast Health, Vienna, Austria (Dr Wagner); Beth Israel Deaconess Medical Center, Boston, Mass (Dr Tung); Mayo Clinic College of Medicine, Rochester, Minn (Dr Couch); Institute Marie Curie, Paris, France (Dr Stoppa-Lyonnet); London Regional Cancer Program, London, Ontario (Dr Ainsworth); Fox Chase Cancer Center, Philadelphia, Pa (Dr Daly); Universita di Torino, Italy (Dr Pasini); Rambam Medical Center, Haifa, Israel (Dr Gershoni-Baruch); Ohio State University, Columbus, Cleveland Clinic Genomic Medicine Institute, Cleveland, Ohio (Dr Eng); University of Chicago, Chicago, Ill (Dr Olopade); Cancer Risk Program, San Francisco, Calif (Dr McLennan); Division of Gynecology Oncology, Cedars Sinai Medical Center, Los Angeles, Calif (Dr Karlan); City of Hope Medical Center, Duarte, Calif (Dr Weitzel).

Corresponding Author: Steven A Narod, MD, Centre for Research in Women's Health, 790 Bay Street, Toronto, Ontario, Canada M5G 1N8 ([email protected]).

Author Contributions: Dr Narod had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Finch, Beiner, Moller, Rosen, Murphy, Ghadirian, Friedman, Olopade, Karlan.

Acquisition of data: Finch, Lubinski, Lynch, Moller, Rosen, Murphy, Ghadirian, Friedman, Foulkes, Kim-Sing, Wagner, Tung, Couch, Stoppa-Lyonnet, Ainsworth, Daly, Pasini, Gershoni-Baruch, Eng, Olopade, McLennan, Karlan, Weitzel.

Analysis and interpretation of data: Finch, Beiner, Lynch, Moller, Rosen, Murphy, Ghadirian, Friedman, Tung, Ainsworth, Olopade, Karlan, Sun.

Drafting of the manuscript: Finch, Beiner, Lynch, Rosen, Murphy, Ghadirian, Friedman, Tung, Olopade, Karlan, Sun.

Critical revision of the manuscript for important intellectual content: Finch, Beiner, Lubinski, Lynch, Moller, Rosen, Murphy, Ghadirian, Friedman, Foulkes, Kim-Sing, Wagner, Couch, Stoppa-Lyonnet, Ainsworth, Daly, Pasini, Gershoni-Baruch, Eng, Olopade, McLennan, Karlan, Weitzel.

Statistical analysis: Finch, Beiner, Moller, Rosen, Murphy, Ghadirian, Friedman, Olopade, Karlan, Sun.

Obtained funding: Lubinski, Rosen, Murphy, Ghadirian, Friedman, Daly, Olopade, Karlan.

Administrative, technical, or material support: Lubinski, Lynch, Rosen, Murphy, Ghadirian, Friedman, Foulkes, Wagner, Stoppa-Lyonnet, Ainsworth, Eng, Olopade, Karlan, Weitzel.

Study supervision: Lubinski, Rosen, Murphy, Ghadirian, Friedman, Gershoni-Baruch, Olopade, Karlan.

Financial Disclosures: None reported.

Funding/Support: This work was supported by a grant from the Canadian Breast Cancer Research Alliance and from National Institutes of Health grant RO1 CA63678.

Role of the Sponsor: The Canadian Breast Cancer Research Alliance did not participate in the design and conduct of the study, nor in the collection, management, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript.

The Hereditary Ovarian Cancer Clinical Study Group: Dawna Gilchrist, MD (University of Alberta, Edmonton, Alberta); Ellen Warner, MD, and Andrea Eisen, MD (Toronto Sunnybrook Regional Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, Ontario); Wendy McKinnon, MS (Vermont Regional Genetic Center, Burlington); Marie Wood, MD (Vermont Cancer Center, The University of Vermont, Burlington); Michael Osborne, MD (Strang Cancer Prevention Center, New York, NY); Howard Saal, MD (Children's Hospital Medical Center, Cincinnati, Ohio); David Fishman, MD (New York University, New York); Ab Chudley, MD (Children's Hospital, The University of Manitoba, Winnipeg, Manitoba); Gad Rennert, MD (Carmel Medical Center, Haifa, Israel); Diane Provencher, MD (CHUM, Hospital Notre-Dame, Montreal, Quebec); Gordon Mills, MD, (M. D. Anderson Cancer Center, Houston, Tex); Edward Lemire, MD (Royal University Hospital, University of Sasketchewan, Saskatoon, Saskatchewan); Sofia Merajver, MD (University of Michigan Medical Center, Ann Arbor). None of the members of the Hereditary Ovarian Cancer Clinical Study Group received compensation from a funding sponsor for their contributions.

Acknowledgment: We thank Nicole Phillips, BSc, and Anna Tulman, BSc, of the Centre for Research in Women's Health, Toronto, Ontario for data management. No compensation was received for their contributions.

JAMA: The Journal of the American Medical Association 296(2):p 185-192, July 12, 2006.

Context

Women with BRCA1 or BRCA2 mutation are often advised to undergo preventive oophorectomy. The effectiveness of this intervention has not been prospectively evaluated in a large cohort.

Objectives

To estimate the incidence of ovarian, fallopian tube, and primary peritoneal cancer in women who carry a deleterious mutation in BRCA1 or BRCA2. To estimate the reduction in risk of these cancers associated with a bilateral prophylactic salpingo-oophorectomy.

Design, Setting, and Participants

Women known to carry a BRCA1 or BRCA2 mutation were identified from an international registry between 1992 and 2003. A total of 1828 carriers at 1 of 32 centers in Canada, the United States, Europe, and Israel completed questionnaires at baseline and follow-up. Participants were observed from the date of study entry until: diagnosis of ovarian, fallopian tube, or peritoneal cancer; death; or the date of the most recent follow-up.

Intervention

Participants were divided into women who had undergone bilateral prophylactic oophorectomy and those who had not.

Main Outcome Measure

The incidence of ovarian, peritoneal, and fallopian tube cancer was determined by survival analysis. The risk reduction associated with prophylactic salpingo-oophorectomy was evaluated by a time-dependent survival analysis, adjusting for covariates.

Results

After a mean follow-up of 3.5 years, 50 incident ovarian, fallopian tube, and peritoneal cancer cases were reported in the cohort. Of the 1828 women, 555 (30%) underwent a bilateral prophylactic salpingo-oophorectomy prior to study entry, 490 (27%) underwent the procedure after entering the study, and 783 (43%) did not undergo the procedure. There were 32 incident cancers diagnosed in women with intact ovaries (1015/100 000 per year). Eleven cancer cases were identified at the time of prophylactic oophorectomy and 7 were diagnosed following prophylactic oophorectomy (217/100 000 per year). The estimated cumulative incidence of peritoneal cancer is 4.3% at 20 years after oophorectomy. The overall (adjusted) reduction in cancer risk associated with bilateral oophorectomy is 80% (multivariate hazard ratio = 0.20; 95% confidence interval, 0.07–0.58; P = .003).

Conclusion

Oophorectomy is associated with reduced risk of ovarian and fallopian tube cancer in high-risk women, although there is a substantial residual risk for peritoneal cancer in BRCA1 and BRCA2 mutation carriers following prophylactic salpingo-oophorectomy.