Journal of the National Cancer Institute Advance Access published online on September 23, 2008
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djn313
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Hormone Therapy and the Risk of Breast Cancer in BRCA1 Mutation Carriers
Affiliations of authors: Sunnybrook Regional Cancer Center, Toronto, Ontario, Canada (AE); Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland (JL, JG); Section of Cancer Genetics, Department of Medical Genetics, The National Hospital, Oslo, Norway (PM); Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, NE (HTL); Daniel Van den Hoed Cancer Center, Rotterdam, The Netherlands (JK); BC Cancer Agency, Vancouver, BC, Canada (CKS); Department of Epidemiology, University of California, Irvine, CA (SLN); Department of Obstetrics and Gynecology, McGill University, Montreal, Quebec, Canada (LG); Epidemiology Research Unit, Research Centre, Centre Hospitalier de l’Universitaire Montréal, CHUM Hôtel Dieu, Montreal, Quebec, Canada (PG); Unit of Medical Genetics, Fondazione IRCCS Istituto Nazionale Tumori, Milano, Italy (SM); CHS National Cancer Control Center, Carmel Medical Center, Haifa, Israel (GR); Oncogenetics Unit, Chaim Sheba Medical Center, Tel-Hashomer, Israel (EF); Lombardi Cancer Center, Georgetown University Medical Center, Washington, DC (CI, ER); University Health Network, Toronto, Ontario, Canada (BR); Fox Chase Cancer Center, Philadelphia, PA (MD); Women's College Research Institute, Women's College Hospital, University of Toronto, Ontario, Canada (PS, SAN)
Correspondence to: Steven A. Narod, MD, Women's College Research Institute, 790 Bay Street, 7th Floor, Women's College Hospital, University of Toronto, Toronto, Ontario, Canada M5G 1N8 (e-mail: steven.narod{at}wchospital.ca).
Background: Hormone therapy (HT) is commonly given to women to alleviate the climacteric symptoms associated with menopause. There is concern that this treatment may increase the risk of breast cancer. The potential association of HT and breast cancer risk is of particular interest to women who carry a mutation in BRCA1 because they face a high lifetime risk of breast cancer and because many of these women take HT after undergoing prophylactic surgical oophorectomy at a young age.
Methods: We conducted a matched case–control study of 472 postmenopausal women with a BRCA1 mutation to examine whether or not the use of HT is associated with subsequent risk of breast cancer. Breast cancer case patients and control subjects were matched with respect to age, age at menopause, and type of menopause (surgical or natural). Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with conditional logistic regression. Statistical tests were two-sided.
Results: In this group of BRCA1 mutation carriers, the adjusted OR for breast cancer associated with ever use of HT compared with never use was 0.58 (95% CI = 0.35 to 0.96; P = .03). In analyses by type of HT, an inverse association with breast cancer risk was observed with use of estrogen only (OR = 0.51, 95% CI = 0.27 to 0.98; P = .04); the association with use of estrogen plus progesterone was not statistically significant (OR = 0.66, 95% CI = 0.34 to 1.27; P = .21).
Conclusion: Among postmenopausal women with a BRCA1 mutation, HT use was not associated with increased risk of breast cancer; indeed, in this population, it was associated with a decreased risk.
| CONTEXT AND CAVEATS Prior knowledge Use of hormone therapy (HT) after menopause may increase the risk of breast cancer in the general population. The effects of HT in women with mutations in the BRCA1 gene, however, are not known. Study design Case–control study of postmenopausal women who carry a BRCA1 mutation to compare the risks of breast cancer among those who used HT and those who did not. Contribution In this study of BRCA1 mutation carriers, a decrease in breast cancer risk was observed among those who took HT compared with those who did not. Implications HT use does not appear to be associated with an increased risk for breast cancer among postmenopausal women who carry a BRCA1 mutation. Indeed, in this study, it was associated with a decreased risk among such women. Limitations The study was relatively small, women who had undergone preventive mastectomy or used tamoxifen were excluded, and the results depended on the participants’ recall of HT use. An average of approximately 5.6 years had elapsed between breast cancer diagnosis and the completion of the questionnaire, so if BRCA1 mutation carriers who previously took HT have shorter survival after breast cancer diagnosis than those who did not take HT, this would have skewed the results in the negative direction that was observed. From the Editors
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Manuscript received February 13, 2008; revised June 30, 2008; accepted August 1, 2008.
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J Natl Cancer Inst 2008 100: 1341-1343.
J Natl Cancer Inst 2008 100: 1337.
J Natl Cancer Inst 2008 100: 1337.
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