Heidi D. Nelson, MD, MPH; Miranda Pappas, MA; Amy Cantor, MD, MPH; Jessica Griffin, MS; 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 the AHRQ. No statement in this report should be construed as an official position of the 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; 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; Jennifer Croswell, MD, MPH, at the AHRQ; and USPSTF 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.
Financial Support: By the AHRQ (contract 290-2012-00015-I, Task Order 2), Rockville, Maryland.
Disclosures: Drs. Nelson, Cantor, and Humphrey; Ms. Pappas; Ms. Griffin; and Ms. Daeges report grants from AHRQ during the conduct of this study. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-0970.
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, email@example.com.
Current Author Addresses: Drs. Nelson, Cantor, and Humphrey; Ms. Pappas; Ms. Griffin; 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, M. Pappas, A. Cantor, L. Humphrey.
Analysis and interpretation of the data: H.D. Nelson, M. Pappas, A. Cantor, J. Griffin, M. Daeges, L. Humphrey.
Drafting of the article: H.D. Nelson, M. Pappas, A. Cantor, L. Humphrey.
Critical revision of the article for important intellectual content: H.D. Nelson, A. Cantor, L. Humphrey.
Final approval of the article: H.D. Nelson, M. Pappas, A. Cantor, J. Griffin, M. Daeges, L. Humphrey.
Provision of study materials or patients: H.D. Nelson, M. Daeges.
Obtaining of funding: H.D. Nelson.
Administrative, technical, or logistic support: H.D. Nelson, M. Pappas, A. Cantor, M. Daeges.
Collection and assembly of data: H.D. Nelson, M. Pappas, A. Cantor, J. Griffin, M. Daeges, L. Humphrey.
This article has been corrected. The original version (PDF) is appended to this article as a Supplement.
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 screening in average-risk women with mammography, magnetic resonance imaging, or ultrasonography that reported on false-positive results, overdiagnosis, anxiety, pain, and radiation exposure.
MEDLINE and Cochrane databases through December 2014.
English-language systematic reviews, randomized trials, and observational studies of screening.
Investigators extracted and confirmed data from studies and dual-rated study quality. Discrepancies were resolved through consensus.
Based on 2 studies of U.S. data, 10-year cumulative rates of false-positive mammography results and biopsies were higher with annual than biennial screening (61% vs. 42% and 7% vs. 5%, respectively) and for women aged 40 to 49 years, those with dense breasts, and those using combination hormone therapy. Twenty-nine studies using different methods reported overdiagnosis rates of 0% to 54%; rates from randomized trials were 11% to 22%. Women with false-positive results reported more anxiety, distress, and breast cancer–specific worry, although results varied across 80 observational studies. Thirty-nine observational studies indicated that some women reported pain during mammography (1% to 77%); of these, 11% to 46% declined future screening. Models estimated 2 to 11 screening-related deaths from radiation-induced cancer per 100 000 women using digital mammography, depending on age and screening interval. Five observational studies of tomosynthesis and mammography indicated increased biopsies but reduced recalls compared with mammography alone.
Studies of overdiagnosis were highly heterogeneous, and estimates varied depending on the analytic approach. Studies of anxiety and pain used different outcome measures. Radiation exposure was based on models.
False-positive results are common and are higher for annual screening, younger women, and women with dense breasts. Although overdiagnosis, anxiety, pain, and radiation exposure may cause harm, their effects on individual women are difficult to estimate and vary widely.
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 syndrome; high-risk lesions (ductal carcinoma in situ, lobular carcinoma in situ, atypical ductal hyperplasia, or atypical lobular hyperplasia); or previous large doses of chest radiation (≥20 Gy) before age 30 y.
† False-positive and false-negative mammography results, biopsy recommendations due to false-positive mammography results, overdiagnosis and resulting overtreatment, anxiety, pain, and radiation exposure.
‡ 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.
§ Mammography (film, digital, or 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.
Appendix Table 1. U.S. Studies of Cumulative False-Positive Mammography and Biopsy Results
Appendix Table 2. Studies of Overdiagnosis With Breast Cancer Screening
Appendix Table 2–Continued
Table 1. Systematic Reviews of Psychological Harms of Breast Cancer Screening
Table 2. Results of New Studies of Psychological Harms of Breast Cancer Screening
Appendix Table 3. Systematic Reviews of Pain With Mammography
Appendix Table 4. Models of Radiation Exposure With Screening, Breast Cancer Incidence, and Death
Appendix Table 5. Studies of Harms of Breast Cancer Screening With Different Modalities
Table 3. Summary of Evidence
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September 7, 2018
Letter to the Editor
The 2016 systematic review to update the 2009 US Preventive Services Taskforce (USPSTF) recommendation on breast cancer screening is available in full through the USPSTF’s website (https://www.uspreventiveservicestaskforce.org/Home/GetFile/1/16475/breastcanscr-final-evidrev/pdf) and the National Library of Medicine (1), but the authors also published three articles in this journal detailing their findings and resulting recommendations, separating the articles by effectiveness (2), harms (3), and recommendations (4). In the article on harms, the USPSTF authors consider – among other estimates of overdiagnosis – the estimate offered by the Malmö trial for the 55-to-69-year-old age group and the Canada I and Canada II trials (the younger age group from the Malmö trial was excluded due to this group being offered screening at the end of the study period (5)). Considering the meta-analytic estimates of overdiagnosis from these trials, the USPSTF authors report (3): “Overdiagnosis was estimated at 10.7% (CI, 9.3% to 12.2%) (13, 14) when only cases identified during the screening period were included and 19.0% (CI, 15.2% to 22.7%) when cases identified throughout screening and follow-up were included.”These rates are flipped. That is, this section should instead read: “Overdiagnosis was estimated at 19.0% (CI, 15.2% to 22.7%) when only cases identified during the screening period were included and 10.7% (CI, 9.3% to 12.2%) when cases identified throughout screening and follow-up were included (13, 14).”References 13 and 14 are for reviews published in the Lancet (6) and the British Journal of Cancer (5), both of which report rates of overdiagnosis matching the corrected phrasing. The USPSTF authors also report the rates correctly in the aforementioned full version of their review (1). Both estimates of overdiagnosis are noteworthy, each method can potentially provide insight into somewhat different questions (5,6), and the estimates decreasing with the long-case accrual method (i.e., including cases identified throughout screening and follow-up) versus the short-case accrual method (i.e., including only cases identified during the screening period) makes sense due to the potential for catch-up cancers to impact the estimates (5–7). Of note, however, the Malmö trial’s denominator (all breast cancer cases, not just those identified with screening) is problematic (1,7,8). When adjusting for this, the Malmö trial data show a higher rate of overdiagnosis (1,7,8) than what appears in the data used for the meta-analytic estimates (5,6). Additionally, recently-published 25-year follow-up data from the Canada trials also report a combined rate of overdiagnosis of approximately 22% (1,9). Acknowledgements: NoneConflicts of interest: None References1. Nelson HD, Cantor A, Humphrey L, Fu R, Pappas M, Daeges M, et al. Screening for Breast Cancer: A Systematic Review to Update the 2009 U.S. Preventive Services Task Force Recommendation [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2016 [cited 2018 Sep 5]. (U.S. Preventive Services Task Force Evidence Syntheses, formerly Systematic Evidence Reviews). Available from: http://www.ncbi.nlm.nih.gov/books/NBK343819/2. 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. 2016 Feb 16;164(4):244. 3. Nelson HD, Pappas M, Cantor A, Griffin J, Daeges M, Humphrey L. Harms of Breast Cancer Screening: Systematic Review to Update the 2009 U.S. Preventive Services Task Force Recommendation. Ann Intern Med. 2016 Feb 16;164(4):256. 4. Siu AL, on behalf of the U.S. Preventive Services Task Force. Screening for Breast Cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med. 2016 Feb 16;164(4):279. 5. Marmot MG, Altman DG, Cameron DA, Dewar JA, Thompson SG, Wilcox M. The benefits and harms of breast cancer screening: an independent review. Br J Cancer. 2013 Jun 11;108(11):2205–40. 6. Independent UK Panel on Breast Cancer Screening. The benefits and harms of breast cancer screening: an independent review. The Lancet. 2012 Nov;380(9855):1778–86. 7. Welch HG, Black WC. Overdiagnosis in Cancer. J Natl Cancer Inst. 2010 May 5;102(9):605–13. 8. Welch HG, Schwartz LM, Woloshin S. Ramifications of screening for breast cancer: 1 in 4 cancers detected by mammography are pseudocancers. BMJ. 2006 Mar 23;332(7543):727. 9. Miller AB, Wall C, Baines CJ, Sun P, To T, Narod SA. Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial. BMJ. 2014 Feb 11;348:g366.
Nelson HD, Pappas M, Cantor A, Griffin J, Daeges M, Humphrey L. Harms of Breast Cancer Screening: Systematic Review to Update the 2009 U.S. Preventive Services Task Force Recommendation. Ann Intern Med. ;164:256–267. doi: 10.7326/M15-0970
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Published: Ann Intern Med. 2016;164(4):256-267.
Published at www.annals.org on 12 January 2016
Breast Cancer, Cancer Screening/Prevention, Hematology/Oncology, Prevention/Screening.
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