Original Research
1 March 2022

Estimation of Breast Cancer Overdiagnosis in a U.S. Breast Screening Cohort

Publication: Annals of Internal Medicine
Volume 175, Number 4
Visual Abstract. Estimation of Breast Cancer Overdiagnosis in a U.S. Breast Screening Cohort.
Overdiagnosis from screening can result from the detection of indolent preclinical cancer or progressive preclinical cancer where the person would have died of an unrelated cause before clinical diagnosis. This article uses statistical modeling to account for both types of overdiagnosis in estimating the rate of screen-detected breast cancer that is overdiagnosed.



Mammography screening can lead to overdiagnosis—that is, screen-detected breast cancer that would not have caused symptoms or signs in the remaining lifetime. There is no consensus about the frequency of breast cancer overdiagnosis.


To estimate the rate of breast cancer overdiagnosis in contemporary mammography practice accounting for the detection of nonprogressive cancer.


Bayesian inference of the natural history of breast cancer using individual screening and diagnosis records, allowing for nonprogressive preclinical cancer. Combination of fitted natural history model with life-table data to predict the rate of overdiagnosis among screen-detected cancer under biennial screening.


Breast Cancer Surveillance Consortium (BCSC) facilities.


Women aged 50 to 74 years at first mammography screen between 2000 and 2018.


Screening mammograms and screen-detected or interval breast cancer.


The cohort included 35 986 women, 82 677 mammograms, and 718 breast cancer diagnoses. Among all preclinical cancer cases, 4.5% (95% uncertainty interval [UI], 0.1% to 14.8%) were estimated to be nonprogressive. In a program of biennial screening from age 50 to 74 years, 15.4% (UI, 9.4% to 26.5%) of screen-detected cancer cases were estimated to be overdiagnosed, with 6.1% (UI, 0.2% to 20.1%) due to detecting indolent preclinical cancer and 9.3% (UI, 5.5% to 13.5%) due to detecting progressive preclinical cancer in women who would have died of an unrelated cause before clinical diagnosis.


Exclusion of women with first mammography screen outside BCSC.


On the basis of an authoritative U.S. population data set, the analysis projected that among biennially screened women aged 50 to 74 years, about 1 in 7 cases of screen-detected cancer is overdiagnosed. This information clarifies the risk for breast cancer overdiagnosis in contemporary screening practice and should facilitate shared and informed decision making about mammography screening.

Primary Funding Source:

National Cancer Institute.

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Supplemental Material

Supplement 1. Technical Appendix

Supplement 2. Supplementary Material


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Information & Authors


Published In

cover image Annals of Internal Medicine
Annals of Internal Medicine
Volume 175Number 4April 2022
Pages: 471 - 478


Published online: 1 March 2022
Published in issue: April 2022




Department of Population Health Sciences, Duke University Medical Center, and Department of Mathematics, Duke University, Durham, North Carolina (M.D.R.)
Jane Lange, PhD
Center for Early Detection Advanced Research, Knight Cancer Institute, Oregon Health Sciences University, Portland, Oregon (J.L.)
Lurdes Y.T. Inoue, PhD
Department of Biostatistics, University of Washington, Seattle, Washington (L.Y.I.)
Ellen S. O’Meara, PhD
Kaiser Permanente Washington Health Research Institute, Seattle, Washington (E.S.O.)
Department of Economics, Applied Statistics, and International Business, New Mexico State University, Las Cruces, New Mexico (C.G.)
Diana L. Miglioretti, PhD https://orcid.org/0000-0002-5547-1833
Division of Biostatistics, Department of Public Health Sciences, University of California, Davis, Davis, California, and Kaiser Permanente Washington Health Research Institute, Seattle, Washington (D.L.M.)
Centre for Primary Care and Public Health (Unisanté), University of Lausanne, Lausanne, Switzerland (J.B.)
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan (A.F.B.)
E. Shelley Hwang, MD, MPH https://orcid.org/0000-0002-8571-1148
Department of Surgery, Duke University Medical Center, Durham, North Carolina (E.S.H.)
Program in Biostatistics, Fred Hutchinson Cancer Research Center, Seattle, Washington (R.B.E.).
Disclaimer: The statements in this report are solely those of the authors and do not necessarily represent the views of the Patient-Centered Outcomes Research Institute and its Board of Governors or Methodology Committee, National Cancer Institute, or National Institutes of Health.
Acknowledgment: The authors thank the participating women, mammography facilities, and radiologists for the data they have provided.
Financial Support: By grants R00CA207872, R01CA242735, and R01CA192492 from the National Institutes of Health. Data collection was additionally supported by the BCSC (www.bcsc-research.org/) with funding from the National Cancer Institute (grants P01CA154292 and U54CA163303) and the Patient-Centered Outcomes Research Institute (grant PCS-1504-30370). Cancer and vital status data collection were supported in part by several U.S. state public health departments and cancer registries (www.bcsc-research.org/about/work-acknowledgement).
Reproducible Research Statement: Study protocol and data set: Not available. Statistical code: Available on GitHub.com/mdryser/BCSC_Overdiagnosis.
Corresponding Author: Marc D. Ryser, PhD, Duke University, 215 Morris Street, Durham, NC 27701; e-mail, [email protected].
Author Contributions: Conception and design: R.B. Etzioni, J. Lange, M.D. Ryser.
Analysis and interpretation of the data: J. Bulliard, R.B. Etzioni, J. Lange, D.L. Miglioretti, M.D. Ryser.
Drafting of the article: R.B. Etzioni, E.S. Hwang, M.D. Ryser.
Critical revision of the article for important intellectual content: A.F. Brouwer, J. Bulliard, R.B. Etzioni, E.S. Hwang, J. Lange, D.L. Miglioretti, M.D. Ryser.
Final approval of the article: A.F. Brouwer, J. Bulliard, R.B. Etzioni, C. Gard, E.S. Hwang, L. Inoue, J. Lange, D.L. Miglioretti, E.S. O’Meara, M.D. Ryser.
Statistical expertise: R.B. Etzioni, L. Inoue, J. Lange, D.L. Miglioretti, M.D. Ryser.
Obtaining of funding: R.B. Etzioni, D.L. Miglioretti, M.D. Ryser.
Administrative, technical, or logistic support: E.S. Hwang.
Collection and assembly of data: R.B. Etzioni, C. Gard, J. Lange, D.L. Miglioretti, E.S. O’Meara, M.D. Ryser.
This article was published at Annals.org on 1 March 2022.

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Marc D. Ryser, Jane Lange, Lurdes Y.T. Inoue, et al. Estimation of Breast Cancer Overdiagnosis in a U.S. Breast Screening Cohort. Ann Intern Med.2022;175:471-478. [Epub 1 March 2022]. doi:10.7326/M21-3577

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