Heidi D. Nelson, MD, MPH; Bernadette Zakher, MBBS; Amy Cantor, MD, MPH; Rongwei Fu, PhD; Jessica Griffin, MS; Ellen S. O'Meara, PhD; Diana S.M. Buist, PhD, MPH; Karla Kerlikowske, MD, MS; Nicolien T. van Ravesteyn, MSc; Amy Trentham-Dietz, PhD; Jeanne S. Mandelblatt, MD, MPH; Diana L. Miglioretti, PhD
Disclaimer: The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute or the National Institutes of Health.
Note: Each cancer registry and the Statistical Coordinating Center have received institutional review board approval for either active or passive consenting processes or a waiver of consent to enroll participants, link data, and perform analytic studies. All procedures are compliant with the Health Insurance Portability and Accountability Act, and all registries and the Statistical Coordinating Center have received a federal Certificate of Confidentiality and other protection for the identities of women, physicians, and facilities participating in this research. A list of the BCSC investigators and procedures for requesting BCSC data for research purposes is provided at http://breastscreening.cancer.gov/.
Acknowledgment: The authors thank the participating women, mammography facilities, and radiologists for the data they have provided for this study. Rose Relevo, MLIS, MS, and Robin Paynter, MA-LIS, conducted literature searches, and Katie Reitel, BA, provided assistance; all are affiliated with Oregon Health & Science University.
Grant Support: By a National Cancer Institute Activities to Promote Research Collaboration supplement (U01CA086076-10S1). Data collection was supported by the National Cancer Institute–funded BCSC cooperative agreements (U01CA63740, U01CA86076, U01CA86082, U01CA63736, U01CA70013, U01CA69976, U01CA63731, and U01CA70040). Providence Health & Services provided additional support for Dr. Nelson, and the Veterans Affairs Fellowship in Health Issues of Women Veterans provided support for Dr. Cantor. The collection of BCSC cancer data used in this study was supported in part by several state public health departments and cancer registries throughout the United States. For a full description of these sources, please see www.breastscreening.cancer.gov/work/acknowledgement.html.
Potential Conflicts of Interest: Dr. Nelson: Grant (money to institution): NCI; Support for travel to meetings for the study or other purposes (money to institution): NCI. Dr Fu: Grant (money to institution): AHRQ. Ms. Griffin: Grant (money to institution): NCI. Dr. O'Meara: Grant (money to institution): NCI; Employment: Group Health Research Institute. Dr. Buist: Grant (money to institution): NCI. Ms. van Ravesteyn: Grant (money to institution): NCI. Dr. Trentham-Dietz: Grant (money to institution): NCI; Support for travel to meetings for the study or other purposes: NCI. Dr. Mandelblatt: Grant (money to institution): NCI; Support for travel to meetings for the study or other purposes (money to institution): NCI. Dr. Miglioretti: Grant (money to institution): NIH. Disclosures can be also viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M11-2350.
Requests for Single Reprints: Heidi D. Nelson, MD, MPH, Oregon Evidence-based Practice Center, Oregon Health & Science University, Mail Code BICC, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098; e-mail, mailto:firstname.lastname@example.org.
Current Author Addresses: Drs. Nelson, Zakher, Cantor, and Fu and Ms. Griffin: 3181 SW Sam Jackson Park Road, Mail Code BICC, Portland, OR 97239.
Drs. O'Meara, Buist, and Miglioretti: 1730 Minor Avenue, Suite 1600, Seattle, WA 98101.
Dr. Kerlikowske: 4150 Clement Street, San Francisco, CA 94121.
Ms. van Ravesteyn: PO Box 2040, Rotterdam 3000, the Netherlands.
Dr. Trentham-Dietz: 307 WARF Building, 610 Walnut Street, Madison, WI 53726.
Dr. Mandelblatt: Suite 4100, 3300 Whitehaven Street NW, Washington, DC 20007.
Author Contributions: Conception and design: H.D. Nelson, D.S.M. Buist, K. Kerlikowske, N. van Ravesteyn, A. Trentham-Dietz, J. Mandelblatt, D. Miglioretti.
Analysis and interpretation of the data: H.D. Nelson, B. Zakher, A. Cantor, R. Fu, J. Griffin, E.S. O'Meara, D.S.M. Buist, K. Kerlikowske, A. Trentham-Dietz, J. Mandelblatt.
Drafting of the article: H.D. Nelson, B. Zakher, A. Cantor, R. Fu, J. Griffin, E.S. O'Meara, K. Kerlikowske, J. Mandelblatt.
Critical revision of the article for important intellectual content: H.D. Nelson, B. Zakher, A. Cantor, R. Fu, D.S.M. Buist, K. Kerlikowske, N. van Ravesteyn, A. Trentham-Dietz, J. Mandelblatt, D. Miglioretti.
Final approval of the article: H.D. Nelson, B. Zakher, R. Fu, J. Griffin, E.S. O'Meara, D.S.M. Buist, K. Kerlikowske, N. van Ravesteyn, J. Mandelblatt, D. Miglioretti.
Provision of study materials or patients: H.D. Nelson, D.S.M. Buist, K. Kerlikowske.
Statistical expertise: H.D. Nelson, R. Fu, K. Kerlikowske, D. Miglioretti.
Obtaining of funding: H.D. Nelson, D.S.M. Buist, K. Kerlikowske, J. Mandelblatt, D. Miglioretti.
Administrative, technical, or logistic support: H.D. Nelson, J. Griffin, D.S.M. Buist.
Collection and assembly of data: H.D. Nelson, B. Zakher, A. Cantor, R. Fu, J. Griffin, D.S.M. Buist, K. Kerlikowske, D. Miglioretti.
Identifying risk factors for breast cancer specific to women in their 40s could inform screening decisions.
To determine what factors increase risk for breast cancer in women aged 40 to 49 years and the magnitude of risk for each factor.
MEDLINE (January 1996 to the second week of November 2011), Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (fourth quarter of 2011), Scopus, reference lists of published studies, and the Breast Cancer Surveillance Consortium.
English-language studies and systematic reviews of risk factors for breast cancer in women aged 40 to 49 years. Additional inclusion criteria were applied for each risk factor.
Data on participants, study design, analysis, follow-up, and outcomes were abstracted. Study quality was rated by using established criteria, and only studies rated as good or fair were included. Results were summarized by using meta-analysis when sufficient studies were available or from the best evidence based on study quality, size, and applicability when meta-analysis was not possible. Data from the Breast Cancer Surveillance Consortium were analyzed with proportional hazards models by using partly conditional Cox regression. Reference groups for comparisons were set at U.S. population means.
Sixty-six studies provided data for estimates. Extremely dense breasts on mammography or first-degree relatives with breast cancer were associated with at least a 2-fold increase in risk for breast cancer. Prior breast biopsy, second-degree relatives with breast cancer, or heterogeneously dense breasts were associated with a 1.5- to 2.0-fold increased risk; current use of oral contraceptives, nulliparity, and age 30 years or older at first birth were associated with a 1.0- to 1.5-fold increased risk.
Studies varied by measures, reference groups, and adjustment for confounders, which could bias combined estimates. Effects of multiple risk factors were not considered.
Extremely dense breasts and first-degree relatives with breast cancer were each associated with at least a 2-fold increase in risk for breast cancer in women aged 40 to 49 years. Identification of these risk factors may be useful for personalized mammography screening.
National Cancer Institute.
Nelson HD, Zakher B, Cantor A, et al. Risk Factors for Breast Cancer for Women Aged 40 to 49 Years: A Systematic Review and Meta-analysis. Ann Intern Med. 2012;156:635–648. doi: https://doi.org/10.7326/0003-4819-156-9-201205010-00006
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Published: Ann Intern Med. 2012;156(9):635-648.
Breast Cancer, Cancer Screening/Prevention, Hematology/Oncology, Prevention/Screening.
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