Heidi D. Nelson, MD, MPH; Rochelle Fu, PhD; Amy Cantor, MD, MPH; Miranda Pappas, MA; Monica Daeges, BA; Linda Humphrey, MD, MPH
Disclaimer: The findings and conclusions in this article are those of the authors, who are responsible for its content, and do not necessarily represent the views of AHRQ. No statement in this report should be construed as an official position of AHRQ or the U.S. Department of Health and Human Services.
Acknowledgment: The authors thank Andrew Hamilton, MLS, MS, for conducting literature searches and Spencer Dandy, BS, for assisting with manuscript preparation at the Pacific Northwest Evidence-based Practice Center at Oregon Health & Science University; and Alison Conlin, MD, MPH, and Michael Neuman, MD, at the Providence Cancer Center at Providence Health and Services Oregon, and Arpana Naik, MD, at Oregon Health & Science University for providing medical expertise. They also thank Jennifer Croswell, MD, MPH, at the Agency for Healthcare Research and Quality, and U.S. Preventive Services Task Force members Linda Baumann, PhD, RN; Kirsten Bibbins-Domingo, PhD, MD, MAS; Mark Ebell, MD, MS; Jessica Herzstein, MD, MPH; Michael LeFevre, MD, MSPH; and Douglas Owens, MD, MS.
Grant Support: By the AHRQ (contract 290-2012-00015-I, Task Order 2), Rockville, Maryland.
Disclosures: Drs. Nelson, Fu, Cantor, and Humphrey; Ms. Pappas; and Ms. Daeges report grants from AHRQ during the conduct of the study. Authors not named here have disclosed no conflicts of interest. Disclosures can also be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?ms Num=M15-0969.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.
Requests for Single Reprints: Heidi D. Nelson, MD, MPH, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code BICC, Portland, OR 97239; e-mail, firstname.lastname@example.org.
Current Author Addresses: Drs. Nelson, Fu, Cantor, and Humphrey; Ms. Pappas; and Ms. Daeges: Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Mail Code BICC, Portland, OR 97239.
Author Contributions: Conception and design: H.D. Nelson, A. Cantor, L. Humphrey.
Analysis and interpretation of the data: H.D. Nelson, R. Fu, A. Cantor, M. Pappas, M. Daeges, L. Humphrey.
Drafting of the article: H.D. Nelson, R. Fu, A. Cantor, M. Pappas, L. Humphrey.
Critical revision of the article for important intellectual content: H.D. Nelson, R. Fu, A. Cantor, L. Humphrey.
Final approval of the article: H.D. Nelson, R. Fu, A. Cantor, M. Pappas.
Provision of study materials or patients: H.D. Nelson, M. Daeges.
Statistical expertise: H.D. Nelson, R. Fu, A. Cantor.
Obtaining of funding: H.D. Nelson.
Administrative, technical, or logistic support: H.D. Nelson, M. Pappas, M. Daeges.
Collection and assembly of data: H.D. Nelson, R. Fu, A. Cantor, M. Pappas, M. Daeges, L. Humphrey.
In 2009, the U.S. Preventive Services Task Force recommended biennial mammography screening for women aged 50 to 74 years and selective screening for those aged 40 to 49 years.
To review studies of the effectiveness of breast cancer screening in average-risk women.
MEDLINE and Cochrane databases to 4 June 2015.
English-language randomized, controlled trials and observational studies of screening with mammography, magnetic resonance imaging, and ultrasonography that reported breast cancer mortality, all-cause mortality, or advanced breast cancer outcomes.
Investigators extracted and confirmed data and dual rated study quality; discrepancies were resolved through consensus.
Fair-quality evidence from a meta-analysis of mammography trials indicated relative risks (RRs) for breast cancer mortality of 0.92 for women aged 39 to 49 years (95% CI, 0.75 to 1.02) (9 trials; 3 deaths prevented per 10 000 women over 10 years); 0.86 for those aged 50 to 59 years (CI, 0.68 to 0.97) (7 trials; 8 deaths prevented per 10 000 women over 10 years); 0.67 for those aged 60 to 69 years (CI, 0.54 to 0.83) (5 trials; 21 deaths prevented per 10 000 women over 10 years); and 0.80 for those aged 70 to 74 years (CI, 0.51 to 1.28) (3 trials; 13 deaths prevented per 10 000 women over 10 years). Risk reduction was 25% to 31% for women aged 50 to 69 years in observational studies of mammography screening. All-cause mortality was not reduced with screening. Advanced breast cancer was reduced for women aged 50 years or older (RR, 0.62 [CI, 0.46 to 0.83]) (3 trials) but not those aged 39 to 49 years (RR, 0.98 [CI, 0.74 to 1.37]) (4 trials); less evidence supported this outcome.
Most trials used imaging technologies and treatments that are now outdated, and definitions of advanced breast cancer were heterogeneous. Studies of effectiveness based on risk factors, intervals, or other modalities were unavailable or methodologically limited.
Breast cancer mortality is generally reduced with mammography screening, although estimates are not statistically significant at all ages and the magnitudes of effect are small. Advanced cancer is reduced with screening for women aged 50 years or older.
Agency for Healthcare Research and Quality.
Analytic framework and key questions.
KQ = key question.
* Excludes women with preexisting breast cancer; clinically significant BRCA1 or BRCA2 mutations, Li–Fraumeni syndrome, Cowden syndrome, hereditary diffuse gastric cancer, or other familial breast cancer syndromes; high-risk lesions (ductal carcinoma in situ, lobular carcinoma in situ, atypical ductal hyperplasia, atypical lobular hyperplasia); or previous large doses of chest radiation (≥20 Gy) before age 30 y.
† Risk factors include family history; breast density; race/ethnicity; menopausal status; current use of menopausal hormone therapy or oral contraceptives; prior benign breast biopsy; and, for women aged >50 y, body mass index.
‡ Morbidity includes physical adverse effects of treatment, quality-of-life measures, and other measures of impairment.
§ Screening modalities include mammography (film, digital, tomosynthesis), magnetic resonance imaging, ultrasonography, and clinical breast examination (alone or in combination).
Summary of evidence search and selection.
RCT = randomized, controlled trial.
* Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews.
† Publications may have been used for multiple key questions.
Appendix Table 1. Mammography Screening Trials
Effects of screening on breast cancer mortality.
Meta-analysis of trials using the longest follow-up times available. CNBSS = Canadian National Breast Screening Study; HIP = Health Insurance Plan of New York; MMST = Malmö Mammographic Screening Trial.
* Used short case accrual.
Table 1. Age-Specific Rates of Breast Cancer Mortality Reduction With Screening
Appendix Table 2. Observational Studies of Screening and Mortality Not Included in Systematic Reviews
Appendix Table 3. Advanced Breast Cancer Outcomes Reported in Screening Trials
Effects of screening on advanced cancer outcomes.
Meta-analysis of trials reporting the most severe disease categories available. CNBSS = Canadian National Breast Screening Study; HIP = Health Insurance Plan of New York.
Appendix Table 4. Studies of Advanced Cancer Outcomes With Mammography Screening
Appendix Table 5. Observational Studies of Breast Cancer Treatment for Screened and Nonscreened Women
Appendix Table 6. Observational Studies of Advanced Cancer Outcomes With Mammography Plus Tomosynthesis
Table 2. Summary of Evidence: Effectiveness of Breast Cancer Screening
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Nelson HD, Fu R, Cantor A, Pappas M, Daeges M, Humphrey L. Effectiveness of Breast Cancer Screening: Systematic Review and Meta-analysis to Update the 2009 U.S. Preventive Services Task Force Recommendation. Ann Intern Med. ;164:244–255. doi: 10.7326/M15-0969
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Published: Ann Intern Med. 2016;164(4):244-255.
Published at www.annals.org on 12 January 2016
Breast Cancer, Hematology/Oncology.
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