Originally published as JCO Early Release 10.1200/JCO.2004.00.8151 on October 11 2005

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Effect of Short-Term Hormone Replacement Therapy on Breast Cancer Risk Reduction After Bilateral Prophylactic Oophorectomy in BRCA1 and BRCA2 Mutation Carriers: The PROSE Study Group

From the Center for Clinical Epidemiology and Biostatistics, Abramson Cancer Center, and Abramson Family Research Institute, The University of Pennsylvania School of Medicine, Philadelphia, PA; Women's College Hospital, Sunnybrook Regional Cancer Centre, Toronto, ON; Medical University of Vienna, Austria; Creighton University, Omaha, NE; Dana-Farber Cancer Institute, Boston, MA; Fox Chase Cancer Center, Philadelphia, PA; Lombardi Cancer Center, Georgetown University, Washington, DC; University of Chicago, Chicago, IL; Division Epidemiology, Department of Medicine, University of California, Irvine, CA; Netherlands Cancer Institute, Amsterdam, the Netherlands; Royal Marsden Hospital, Sutton; St Mary's Hospital, Manchester, UK; University of Texas Southwestern Medical Center at Dallas, Dallas, TX; and Yale University, New Haven, CT.

Address reprint requests to Timothy R. Rebbeck, PhD, University of Pennsylvania School of Medicine, 904 Blockley Hall, Philadelphia, PA 19104; e-mail: trebbeck{at}cceb.med.upenn.edu

PURPOSE: Bilateral prophylactic oophorectomy (BPO) is widely used for cancer risk reduction in women with BRCA1/2 mutations. Many premenopausal women choose to take hormone replacement therapy (HRT) after undergoing BPO to abrogate immediate symptoms of surgically-induced menopause. Thus, we evaluated whether the breast cancer risk reduction conferred by BPO in BRCA1/2 mutation carriers is altered by use of post-BPO HRT.

METHODS: We identified a prospective cohort of 462 women with disease-associated germline BRCA1/2 mutations at 13 medical centers to evaluate breast cancer risk after BPO with and without HRT. We determined the incidence of breast cancer in 155 women who had undergone BPO and in 307 women who had not undergone BPO on whom we had complete information on HRT use. Postoperative follow-up was 3.6 years.

RESULTS: Consistent with previous reports, BPO was significantly associated with breast cancer risk reduction overall (hazard ratio [HR] = 0.40; 95%CI, 0.18 to 0.92). Using mutation carriers without BPO or HRT as the referent group, HRT of any type after BPO did not significantly alter the reduction in breast cancer risk associated with BPO (HR = 0.37; 95% CI, 0.14 to 0.96).

CONCLUSION: Short-term HRT use does not negate the protective effect of BPO on subsequent breast cancer risk in BRCA1/2 mutation carriers.

Supported by grants from the Public Health Service (R01-CA83855 to T.R.R.; CA74415 to S.L.N.), the University of Pennsylvania Cancer Center (to T.R.R. and B.L.W.), The Breast Cancer Research Foundation (to B.L.W.), the Dana-Farber Women's Cancers Program (to J.E.G.), the Department of Defense (DAMD-17-96-I-6088 to A.K.G.; DAMD-17-94-J-4340 and DAMD-17-97-I-7112 to H.T.L.), The Utah Cancer registry (funded by Public Health Service Grant NO1-CN-6700) and the Utah State Department of Health, and the Nebraska State Cancer and Smoking-Related Diseases Research Program (LB595 to H.T.L.). B.L.W. is an Investigator of the Abramson Family Cancer Research Institute at the University of Pennsylvania. O.I.O. is Doris Duke Distinguished Clinical Scientist.

Authors' disclosures of potential conflicts of interest are found at the end of this article.

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