© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 17, 1475-1479,
September 1, 1999
© 1999 Oxford University Press
REPORTS |
Breast Cancer Risk After Bilateral Prophylactic Oophorectomy in BRCA1 Mutation Carriers
Affiliations of authors: T. R. Rebbeck, A. Eisen, B. L. Weber, Departments of Biostatistics and Epidemiology, Medicine, and Genetics, University of Pennsylvania School of Medicine, Philadelphia; A. M. Levin, Karmanos Cancer Institute, Detroit, MI; C. Snyder, P. Watson, H. T. Lynch, Department of Preventive Medicine, Creighton University, Omaha, NE; L. Cannon-Albright, S. L. Neuhausen, Department of Genetic Epidemiology, University of Utah, Salt Lake City; C. Isaacs, Department of Medicine, Georgetown University, Washington, DC; O. Olopade, Department of Medicine, University of Chicago, IL; J. E. Garber, Department of Cancer Epidemiology and Control, Dana-Farber Cancer Institute, Boston, MA; A. K. Godwin, M. B. Daly, Divisions of Basic and Population Science, Fox Chase Cancer Center, Philadelphia, PA; S. A. Narod, Women's College Hospital, Toronto, ON, Canada.
Correspondence to: Timothy R. Rebbeck, Ph.D., University of Pennsylvania School of Medicine, 904 Blockley Hall, 23 Guardian Dr., Philadelphia, PA 19104-6021 (e-mail: trebbeck{at}cceb.med.upenn.edu).
BACKGROUND: The availability of genetic testing for inherited mutations in the BRCA1 gene provides potentially valuable information to women at high risk of breast or ovarian cancer; however, carriers of BRCA1 mutations have few clinical management options to reduce their cancer risk. Decreases in ovarian hormone exposure following bilateral prophylactic oophorectomy (i.e., surgical removal of the ovaries) may alter cancer risk in BRCA1 mutation carriers. This study was undertaken to evaluate whether bilateral prophylactic oophorectomy is associated with a reduction in breast cancer risk in BRCA1 mutation carriers. METHODS: We studied a cohort of women with disease-associated germline BRCA1 mutations who were assembled from five North American centers. Surgery subjects (n = 43) included women with BRCA1 mutations who underwent bilateral prophylactic oophorectomy but had no history of breast or ovarian cancer and had not had a prophylactic mastectomy. Control subjects included women with BRCA1 mutations who had no history of oophorectomy and no history of breast or ovarian cancer (n = 79). Control subjects were matched to the surgery subjects according to center and year of birth. RESULTS: We found a statistically significant reduction in breast cancer risk after bilateral prophylactic oophorectomy, with an adjusted hazard ratio (HR) of 0.53 (95% confidence interval [CI] = 0.33-0.84). This risk reduction was even greater in women who were followed 5-10 (HR = 0.28; 95% CI = 0.08-0.94) or at least 10 (HR = 0.33; 95% CI = 0.12-0.91) years after surgery. Use of hormone replacement therapy did not negate the reduction in breast cancer risk after surgery. CONCLUSIONS: Bilateral prophylactic oophorectomy is associated with a reduced breast cancer risk in women who carry a BRCA1 mutation. The likely mechanism is reduction of ovarian hormone exposure. These findings have implications for the management of breast cancer risk in women who carry BRCA1 mutations.
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V. G. Vogel Reducing the Risk of Breast Cancer With Tamoxifen in Women at Increased Risk J. Clin. Oncol., September 15, 2001; 19(90001): 87s - 92. [Abstract] [Full Text] [PDF]
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E. Warner, D. B. Plewes, R. S. Shumak, G. C. Catzavelos, L. S. Di Prospero, M. J. Yaffe, V. Goel, E. Ramsay, P. L. Chart, D. E.C. Cole, et al. Comparison of Breast Magnetic Resonance Imaging, Mammography, and Ultrasound for Surveillance of Women at High Risk for Hereditary Breast Cancer J. Clin. Oncol., August 1, 2001; 19(15): 3524 - 3531. [Abstract] [Full Text] [PDF]
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I. Kuter Breast Cancer Oncologist, August 1, 2001; 6(4): 338 - 346. [Abstract] [Full Text] [PDF]
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H. Meijers-Heijboer, B. van Geel, W. L.J. van Putten, S. C. Henzen-Logmans, C. Seynaeve, M. B.E. Menke-Pluymers, C. C.M. Bartels, L. C. Verhoog, A. M.W. van den Ouweland, M. F. Niermeijer, et al. Breast Cancer after Prophylactic Bilateral Mastectomy in Women with a BRCA1 or BRCA2 Mutation N. Engl. J. Med., July 19, 2001; 345(3): 159 - 164. [Abstract] [Full Text] [PDF]
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A. Eisen and B. L. Weber Prophylactic Mastectomy for Women with BRCA1 and BRCA2 Mutations -- Facts and Controversy N. Engl. J. Med., July 19, 2001; 345(3): 207 - 208. [Full Text] [PDF]
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 T. R. Rebbeck, Y. Wang, P. W. Kantoff, K. Krithivas, S. L. Neuhausen, A. K. Godwin, M. B. Daly, S. A. Narod, J.-S. Brunet, D. Vesprini, et al. Modification of BRCA1- and BRCA2-associated Breast Cancer Risk by AIB1 Genotype and Reproductive History Cancer Res., July 1, 2001; 61(14): 5420 - 5424. [Abstract] [Full Text] [PDF]
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J. Chang, S. G. Hilsenbeck, J. H. Sng, J. Wong, and G. C. Ragu Pathological Features and BRCA1 Mutation Screening in Premenopausal Breast Cancer Patients Clin. Cancer Res., June 1, 2001; 7(6): 1739 - 1742. [Abstract] [Full Text] [PDF]
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A.-M. Martin, M.A. Blackwood, D. Antin-Ozerkis, H.A. Shih, K. Calzone, T.A. Colligon, S. Seal, N. Collins, M.R. Stratton, B.L. Weber, et al. Germline Mutations in BRCA1 and BRCA2 in Breast-Ovarian Families From a Breast Cancer Risk Evaluation Clinic J. Clin. Oncol., April 15, 2001; 19(8): 2247 - 2253. [Abstract] [Full Text] [PDF]
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N. F. Col, L. K. Hirota, R. K. Orr, J. K. Erban, J. B. Wong, and J. Lau Hormone Replacement Therapy After Breast Cancer: A Systematic Review and Quantitative Assessment of Risk J. Clin. Oncol., April 15, 2001; 19(8): 2357 - 2363. [Abstract] [Full Text] [PDF]
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 E. Levy-Lahad, A. Lahad, S. Eisenberg, E. Dagan, T. Paperna, L. Kasinetz, R. Catane, B. Kaufman, U. Beller, P. Renbaum, et al. A single nucleotide polymorphism in the RAD51 gene modifies cancer risk in BRCA2 but not BRCA1 carriers PNAS, March 13, 2001; 98(6): 3232 - 3236. [Abstract] [Full Text] [PDF]
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J. M.E. Walsh, N. C. Dolan, and P. Charney Update in Women's Health Ann Intern Med, November 21, 2000; 133(10): 808 - 814. [Full Text] [PDF]
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R. A. Eeles and T. J. Powles Chemoprevention Options for BRCA1 and BRCA2 Mutation Carriers J. Clin. Oncol., November 1, 2000; 18(90001): 93s - 99. [Abstract] [Full Text] [PDF]
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T. R. Rebbeck Prophylactic Oophorectomy in BRCA1 and BRCA2 Mutation Carriers J. Clin. Oncol., November 1, 2000; 18(90001): 100s - 103. [Abstract] [Full Text] [PDF]
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L. J. Pierce, M. Strawderman, S. A. Narod, I. Oliviotto, A. Eisen, L. Dawson, D. Gaffney, L. J. Solin, A. Nixon, J. Garber, et al. Effect of Radiotherapy After Breast-Conserving Treatment in Women With Breast Cancer and Germline BRCA1/2 Mutations J. Clin. Oncol., October 19, 2000; 18(19): 3360 - 3369. [Abstract] [Full Text] [PDF]
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L. Hilakivi-Clarke Estrogens, BRCA1, and Breast Cancer Cancer Res., September 1, 2000; 60(18): 4993 - 5001. [Abstract] [Full Text]
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C. J. Fabian, B. F. Kimler, C. M. Zalles, J. R. Klemp, S. Kamel, S. Zeiger, and M. S. Mayo Short-Term Breast Cancer Prediction by Random Periareolar Fine-Needle Aspiration Cytology and the Gail Risk Model J Natl Cancer Inst, August 2, 2000; 92(15): 1217 - 1227. [Abstract] [Full Text] [PDF]
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R. T. Chlebowski Reducing the Risk of Breast Cancer N. Engl. J. Med., July 20, 2000; 343(3): 191 - 198. [Full Text] [PDF]
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G. M. Petersen Familial Aggregation: Sorting Susceptibility From Shared Environment J Natl Cancer Inst, July 19, 2000; 92(14): 1114 - 1115. [Full Text] [PDF]
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K. H. Lu, J. E. Garber, D. W. Cramer, W. R. Welch, J. Niloff, D. Schrag, R. S. Berkowitz, and M. G. Muto Occult Ovarian Tumors in Women With BRCA1 or BRCA2 Mutations Undergoing Prophylactic Oophorectomy J. Clin. Oncol., July 14, 2000; 18(14): 2728 - 2732. [Abstract] [Full Text] [PDF]
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L. M. Bennett, K. A. McAllister, J. Malphurs, T. Ward, N. K. Collins, J. C. Seely, L. C. Gowen, B. H. Koller, B. J. Davis, and R. W. Wiseman Mice Heterozygous for a Brca1 or Brca2 Mutation Display Distinct Mammary Gland and Ovarian Phenotypes in Response to Diethylstilbestrol Cancer Res., July 1, 2000; 60(13): 3461 - 3469. [Abstract] [Full Text]
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A. Eisen, T. R. Rebbeck, W. C. Wood, and B. L. Weber Prophylactic Surgery in Women With a Hereditary Predisposition to Breast and Ovarian Cancer J. Clin. Oncol., May 9, 2000; 18(9): 1980 - 1995. [Abstract] [Full Text] [PDF]
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D. Schrag, K. M. Kuntz, J. E. Garber, and J. C. Weeks Life Expectancy Gains From Cancer Prevention Strategies for Women With Breast Cancer and BRCA1 or BRCA2 Mutations JAMA, February 2, 2000; 283(5): 617 - 624. [Abstract] [Full Text] [PDF]
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J. Garber A 40-Year-Old Woman With a Strong Family History of Breast Cancer JAMA, November 24, 1999; 282(20): 1953 - 1960. [Full Text] [PDF]
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S. M. Lippman and P. H. Brown Tamoxifen Prevention of Breast Cancer: an Instance of the Fingerpost J Natl Cancer Inst, November 3, 1999; 91(21): 1809 - 1819. [Full Text] [PDF]
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K. J. Helzlsouer Bad News/Good News: Information About Breast Cancer Risk Following Prophylactic Oophorectomy J Natl Cancer Inst, September 1, 1999; 91(17): 1442 - 1443. [Full Text] [PDF]
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