Effect of Reproductive Factors and Oral Contraceptives on Breast Cancer Risk in BRCA1/2 Mutation Carriers and Noncarriers: Results from a Population-Based Study
- Eunjung Lee1,
- Huiyan Ma2,
- Roberta McKean-Cowdin1,
- David Van Den Berg1,
- Leslie Bernstein2,
- Brian E. Henderson1 and
- Giske Ursin1,3
- 1Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California; 2City of Hope Comprehensive Cancer Center and Beckman Research Institute, Duarte, California; and 3Department of Nutrition, University of Oslo, Oslo, Norway
- Requests for reprints:
Giske Ursin, Department of Preventive Medicine, Keck School of Medicine, University of Southern California/Norris Comprehensive Cancer Center, Room 4407, 1441 Eastlake Avenue, Los Angeles, CA 90089. Phone: 323-865-0423; Fax: 323-865-0142. E-mail: gursin{at}usc.edu
Abstract
Background: Multiparity and breast-feeding reduce breast cancer risk, whereas oral contraceptive use may slightly increase breast cancer risk in the general population. However, the effects of these factors in BRCA1 and BRCA2 mutation carriers are less clear.
Methods: Case patients were 1,469 women from Los Angeles County ages 20 to 49 years with newly diagnosed breast cancer. Control subjects were 444 women without breast cancer, individually matched to a subset of cases on race, age, and neighborhood. BRCA1/2 genes were sequenced in the cases, and odds ratios of breast cancer associated with various reproductive and hormonal factors in BRCA1/2 mutation carriers and noncarriers were estimated using multivariable logistic regression.
Results: Ninety-four women had a deleterious BRCA1 or BRCA2 mutation. Number of full-term pregnancies was inversely associated with breast cancer risk regardless of BRCA1/2 mutation status. Longer breast-feeding duration was protective among noncarriers but not among mutation carriers; however, this apparent effect modification was not statistically significant (P = 0.23). Neither oral contraceptive use overall nor the use of low-dose oral contraceptives was associated with an increased risk of breast cancer in any subgroup.
Conclusions: Our results suggest that parity protects against breast cancer in BRCA1/2 mutation carriers, whereas breast-feeding does not. Our data suggest no association between oral contraceptive use and breast cancer risk in BRCA1/2 mutation carriers. Further confirmation that currently available low-dose oral contraceptives do not increase breast cancer risk in carriers is important from a public health perspective given the high prevalence of oral contraceptive use in the United States. (Cancer Epidemiol Biomarkers Prev 2008;17(11):3170–8)
Footnotes
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Grant support: CA17054 and CA74847 from the National Cancer Institute, National Institutes of Health, 4PB-0092 from the California Breast Cancer Research Program of the University of California, and in part through contract no. N01-PC-35139, and T32 ES-013678 from the National Institute of Environmental Health Sciences, National Institute of Health. The collection of cancer incidence data used in this publication was supported by the California Department of Health Services as part of the statewide cancer reporting program mandated by California Health and Safety Code Section 103885. The ideas and opinions expressed herein are those of the authors, and no endorsement by the State of California, Department of Health Services is intended or should be inferred.
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- Accepted August 5, 2008.
- Received May 14, 2008.
- Revision received July 7, 2008.
