Originally published as JCO Early Release 10.1200/JCO.2004.04.188 on February 23 2004
Journal of Clinical Oncology, Vol 22, No 6 (March 15), 2004: pp. 1055-1062
© 2004 American Society of Clinical Oncology.
Bilateral Prophylactic Mastectomy Reduces Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers: The PROSE Study Group
Timothy R. Rebbeck,
Tara Friebel,
Henry T. Lynch,
Susan L. Neuhausen,
Laura van ’t Veer,
Judy E. Garber,
Gareth R. Evans,
Steven A. Narod,
Claudine Isaacs,
Ellen Matloff,
Mary B. Daly,
Olufunmilayo I. Olopade,
Barbara L. Weber
From the PROSE Study Group; the Center for Clinical Epidemiology and Biostatistics, Abramson Family Cancer Research Institute, The University of Pennsylvania; and Fox Chase Cancer Center, Philadelphia, PA; Creighton University, Omaha, NE; Division of Genetic Epidemiology, Department of Medicine, University of California Irvine, Irvine, CA; Women’s College Hospital, Toronto, Ontario, Canada; the Netherlands Cancer Institute, Amsterdam, the Netherlands; Dana-Farber Cancer Institute, Boston, MA; St. Mary’s Hospital, Manchester, United Kingdom; Lombardi Cancer Center, Georgetown University, Washington, DC; Yale University, New Haven, CT; and University of Chicago, Chicago, IL. A list of additional PROSE Study Group members and affiliations appears in the Appendix (online only)
Address reprint requests to Barbara L. Weber, MD, Abramson Family Cancer Research Institute, University of Pennsylvania, 514 BRB2, 421 Curie Blvd, Philadelphia, PA 19104-6021; e-mail: weberb{at}mail.med.upenn.edu
PURPOSE: Data on the efficacy of bilateral prophylactic mastectomy for breast cancer risk reduction in women with BRCA1 and BRCA2 (BRCA1/2) mutations are limited, despite the clinical use of this risk-management strategy. Thus, we estimated the degree of breast cancer risk reduction after surgery in women who carry these mutations.
PATIENTS AND METHODS: Four hundred eighty-three women with disease-associated germline BRCA1/2 mutations were studied for the occurrence of breast cancer. Cases were mutation carriers who underwent bilateral prophylactic mastectomy and who were followed prospectively from the time of their center ascertainment and their surgery, with analyses performed for both follow-up periods. Controls were BRCA1/2 mutation carriers with no history of bilateral prophylactic mastectomy matched to cases on gene, center, and year of birth. Both cases and controls were excluded for previous or concurrent diagnosis of breast cancer. Analyses were adjusted for duration of endogenous ovarian hormone exposure, including age at bilateral prophylactic oophorectomy if applicable.
RESULTS: Breast cancer was diagnosed in two (1.9%) of 105 women who had bilateral prophylactic mastectomy and in 184 (48.7%) of 378 matched controls who did not have the procedure, with a mean follow-up of 6.4 years. Bilateral prophylactic mastectomy reduced the risk of breast cancer by approximately 95% in women with prior or concurrent bilateral prophylactic oophorectomy and by approximately 90% in women with intact ovaries.
CONCLUSION: Bilateral prophylactic mastectomy reduces the risk of breast cancer in women with BRCA1/2 mutations by approximately 90%.
Supported by grants from the National Institutes of Health (grant Nos. R01-CA83855 to T.R.R. and B.L.W.; CA57601 to B.L.W.; and CA74415 to S.L.N.), the Abramson Cancer Center (T.R.R.), the Abramson Family Cancer Research Institute (B.L.W.), the Breast Cancer Research Foundation (B.L.W.), the Dana-Farber Women’s Cancers Program (J.E.G.), the Department of Defense (grant Nos. DAMD-17-96-I-6088 to A.K.G., DAMD-17-94-J-4340 and DAMD-17-99-1-9123 to O.I.O., and DAMD-17-97-I-7112 to H.T.L.), the Utah Cancer Registry (funded by a National Institutes of Health grant No. NO1-CN-6700, the Falk Medical Research Trust [O.I.O.], and the Utah State Department of Health), and the Nebraska State Cancer and Smoking-Related Diseases Research Program (grant No. LB595 to H.T.L.). O.I.O. is a Doris Duke Distinguished Clinical Scientist.
Authors’ disclosures of potential conflicts of interest are found at the end of this article.
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N. J. Agnantis, E. Paraskevaidis, and D. Roukos
Editorial: Preventing Breast, Ovarian Cancer in BRCA Carriers: Rational of Prophylactic Surgery and Promises of Surveillance
Ann. Surg. Oncol.,
December 1, 2004;
11(12):
1030 - 1034.
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R. Sifri, S. Gangadharappa, and L. S. Acheson
Identifying and Testing for Hereditary Susceptibility to Common Cancers
CA Cancer J Clin,
November 1, 2004;
54(6):
309 - 326.
[Abstract]
[Full Text]
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F. Meric-Bernstam
Serum Proteomics for BRCA1-associated Breast Cancer
Ann. Surg. Oncol.,
October 1, 2004;
11(10):
883 - 884.
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M. E. Robson and K. Offit
Breast MRI for Women With Hereditary Cancer Risk
JAMA,
September 15, 2004;
292(11):
1368 - 1370.
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S. Wacholder
Bias in Intervention Studies That Enroll Patients From High-Risk Clinics
J Natl Cancer Inst,
August 18, 2004;
96(16):
1204 - 1207.
[Abstract]
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L. C. Hartmann, A. Degnim, and D. J. Schaid
Prophylactic Mastectomy for BRCA1/2 Carriers: Progress and More Questions
J. Clin. Oncol.,
March 15, 2004;
22(6):
981 - 983.
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