Originally published as JCO Early Release 10.1200/JCO.2007.13.9626 on February 11 2008

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Risk-Reducing Salpingo-Oophorectomy for the Prevention of BRCA1- and BRCA2-Associated Breast and Gynecologic Cancer: A Multicenter, Prospective Study

Noah D. Kauff, Susan M. Domchek, Tara M. Friebel, Mark E. Robson, Johanna Lee, Judy E. Garber, Claudine Isaacs, D. Gareth Evans, Henry Lynch, Rosalind A. Eeles, Susan L. Neuhausen, Mary B. Daly, Ellen Matloff, Joanne L. Blum, Paul Sabbatini, Richard R. Barakat, Clifford Hudis, Larry Norton, Kenneth Offit, Timothy R. Rebbeck

From the Memorial Sloan-Kettering Cancer Center, New York, NY; Abramson Cancer Center and the Center for Clinical Epidemiology and Biostatistics University of Pennsylvania; Fox Chase Cancer Center, Philadelphia, PA; Dana-Farber Cancer Institute, Boston, MA; Lombardi Comprehensive Cancer Center, Washington, DC; Manchester Regional Genetics Service, Manchester, United Kingdom; Creighton University School of Medicine, Omaha, NE; The Institute of Cancer Research, Sutton, United Kingdom; University of California at Irvine, Irvine, CA; Yale University, New Haven, CT; and the Baylor-Charles A. Sammons Cancer Center, Dallas, TX

Corresponding author: Noah D. Kauff, MD, Clinical Genetics and Gynecology Services, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 192, New York, NY 10021; e-mail: kauffn{at}mskcc.org

Purpose: Risk-reducing salpingo-oophorectomy (RRSO) has been widely adopted as a key component of breast and gynecologic cancer risk-reduction for women with BRCA1 and BRCA2 mutations. Despite 17% to 39% of all BRCA mutation carriers having a mutation in BRCA2, no prospective study to date has evaluated the efficacy of RRSO for the prevention of breast and BRCA-associated gynecologic (ovarian, fallopian tube or primary peritoneal) cancer when BRCA2 mutation carriers are analyzed separately from BRCA1 mutation carriers.

Patients and Methods: A total of 1,079 women 30 years of age and older with ovaries in situ and a deleterious BRCA1 or BRCA2 mutation were enrolled onto prospective follow-up studies at one of 11 centers from November 1, 1994 to December 1, 2004. Women self-selected RRSO or observation. Follow-up information through November 30, 2005, was collected by questionnaire and medical record review. The effect of RRSO on time to diagnosis of breast or BRCA-associated gynecologic cancer was analyzed using a Cox proportional-hazards model.

Results: During 3-year follow-up, RRSO was associated with an 85% reduction in BRCA1-associated gynecologic cancer risk (hazard ratio [HR] = 0.15; 95% CI, 0.04 to 0.56) and a 72% reduction in BRCA2-associated breast cancer risk (HR = 0.28; 95% CI, 0.08 to 0.92). While protection against BRCA1-associated breast cancer (HR = 0.61; 95% CI, 0.30 to 1.22) and BRCA2-associated gynecologic cancer (HR = 0.00; 95% CI, not estimable) was suggested, neither effect reached statistical significance.

Conclusion: The protection conferred by RRSO against breast and gynecologic cancers may differ between carriers of BRCA1 and BRCA2 mutations. Further studies evaluating the efficacy of risk-reduction strategies in BRCA mutation carriers should stratify by the specific gene mutated.

published online ahead of print at www.jco.org on February 11, 2008.

Supported in part by the Department of Defense Breast Cancer Research Program (DAMD17-03-1-0375 to N.D.K., DAMD-17-03-1-0619 to S.M.D.), the US Public Health Service (R01-CA83855 to T.R.R., R01-CA102776 to T.R.R., R01-CA74415 to S.L.N.), Cancer Research UK (C5047/A3354 to R.A.E.) the Lucius N. Littauer Foundation, the Frankel Foundation, the Genet Fund, the Koodish Fellowship Fund, the Project Hope Fund for Ovarian Cancer Research and Education, QVC Network, the Fashion Footwear Association of New York, the Edward Spiegel Memorial Fund, revenue from Nebraska cigarette taxes awarded to Creighton University by the Nebraska Department of Health and Human Services, the Charles F. and Mary C. Heider Chair in Cancer Research at Creighton University, the University of Pennsylvania Cancer Center, and the Prevention, Control, and Population Research Program of Memorial Sloan-Kettering Cancer Center.

Presented in part at the 42nd Annual Meeting of the American Society of Clinical Oncology, June 2-6, 2006, Atlanta, GA.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.