Article | Published:


Long-term risk of screen-detected and interval breast cancer after false-positive results at mammography screening: joint analysis of three national cohorts

British Journal of Cancervolume 120pages269275 (2019) | Download Citation



We assessed the long-term risk of screen-detected and interval breast cancer in women with a first or second false-positive screening result.


Joint analysis had been performed using individual-level data from three population-based screening programs in Europe (Copenhagen in Denmark, Norway, and Spain). Overall, 75,513 screened women aged 50–69 years from Denmark (1991–2010), 556,640 from Norway (1996–2008), and 517,314 from Spain (1994–2010) were included. We used partly conditional Cox hazards models to assess the association between false-positive results and the risk of subsequent screen-detected and interval cancer.


During follow-up, 1,149,467 women underwent 3,510,450 screening exams, and 10,623 screen-detected and 5700 interval cancers were diagnosed. Compared to women with negative tests, those with false-positive results had a two-fold risk of screen-detected (HR = 2.04, 95% CI: 1.93–2.16) and interval cancer (HR = 2.18, 95% CI: 2.02–2.34). Women with a second false-positive result had over a four-fold risk of screen-detected and interval cancer (HR = 4.71, 95% CI: 3.81–5.83 and HR = 4.22, 95% CI: 3.27–5.46, respectively). Women remained at an elevated risk for 12 years after the false-positive result.


Women with prior false-positive results had an increased risk of screen-detected and interval cancer for over a decade. This information should be considered to design personalised screening strategies based on individual risk.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.


  1. 1.

    Brett, J., Bankhead, C., Henderson, B., Watson, E. & Austoker, J. The psychological impact of mammographic screening. A systematic review. Psychooncology 14, 917–938 (2005).

  2. 2.

    Bond, M. et al. Systematic review of the psychological consequences of false-positive screening mammograms. Health Technol. Assess. 17, 1–170 (2013). v–vi.

  3. 3.

    Salz, T., Defrank, J. T. & Brewer, N. T. False positive mammograms in Europe: do they affect reattendance? Breast Cancer Res. Treat. 127, 229–231 (2011).

  4. 4.

    Roman, M. et al. The cumulative risk of false-positive results in the Norwegian Breast Cancer Screening Program: updated results. Cancer 119, 3952–3958 (2013).

  5. 5.

    Hofvind, S. et al. False-positive results in mammographic screening for breast cancer in Europe: a literature review and survey of service screening programmes. J. Med. Screen. 19(Suppl. 1), 57–66 (2012).

  6. 6.

    Henderson, L. M., Hubbard, R. A., Sprague, B. L., Zhu, W. & Kerlikowske, K. Increased risk of developing breast cancer after a false-positive screening mammogram. Cancer Epidemiol. Biomark. Prev. 24, 1882–1889 (2015).

  7. 7.

    Barlow, W. E. et al. Prospective breast cancer risk prediction model for women undergoing screening mammography. J. Natl Cancer Inst. 98, 1204–1214 (2006).

  8. 8.

    Castells, X. et al. Breast cancer detection risk in screening mammography after a false-positive result. Cancer Epidemiol. 37, 85–90 (2013).

  9. 9.

    von Euler-Chelpin, M., Risor, L. M., Thorsted, B. L. & Vejborg, I. Risk of breast cancer after false-positive test results in screening mammography. J. Natl Cancer Inst. 104, 682–689 (2012).

  10. 10.

    McCann, J., Stockton, D. & Godward, S. Impact of false-positive mammography on subsequent screening attendance and risk of cancer. Breast Cancer Res. 4, R11 (2002).

  11. 11.

    Roman, M., Castells, X., Hofvind, S. & von Euler-Chelpin, M. Risk of breast cancer after false-positive results in mammographic screening. Cancer Med. 5, 1298–1306 (2016).

  12. 12.

    Peeters, P. H. et al. Breast cancer risk for women with a false positive screening test. Br. J. Cancer 58, 211–212 (1988).

  13. 13.

    von Euler-Chelpin, M., Kuchiki, M. & Vejborg, I. Increased risk of breast cancer in women with false-positive test: the role of misclassification. Cancer Epidemiol. 38, 619–622 (2014).

  14. 14.

    Perry, N. et al. European guidelines for quality assurance in breast cancer screening and diagnosis. (2006).

  15. 15.

    Ascunce, N. et al. Cancer screening in Spain. Annonc Suppl. 21(Suppl. 3), iii43–iii51 (2010).

  16. 16.

    Castells, X. et al. Descripción del cribado del cáncer en España. Proyecto DESCRIC [Internet]. Madrid: Plan de Calidad para el Sistema Nacional de Salud. Ministerio de Sanidad y Consumo. Agència d’Avaluació de Tecnologia i Recerca Mèiques de Cataluña; (2007; 2006).

  17. 17.

    Hofvind, S., Geller, B., Vacek, P. M., Thoresen, S. & Skaane, P. Using the European guidelines to evaluate the Norwegian Breast Cancer Screening Program. Eur. J. Epidemiol. 22, 447–455 (2007).

  18. 18.

    Jacobsen, K. K. & von Euler-Chelpin, M. Performance indicators for participation in organized mammography screening. J. Public Health Oxf. 34, 272–278 (2012).

  19. 19.

    Utzon-Frank, N., Vejborg, I., von Euler-Chelpin, M. & Lynge, E. Balancing sensitivity and specificity: sixteen year’s of experience from the mammography screening programme in Copenhagen, Denmark. Cancer Epidemiol. 35, 393–398 (2011).

  20. 20.

    Zheng, Y. & Heagerty, P. J. Partly conditional survival models for longitudinal data. Biometrics 61, 379–391 (2005).

  21. 21.

    Groenendijk, R. P. et al. Detection of breast cancer after biopsy for false-positive screening mammography. An increased risk? Eur. J. Surg. Oncol. 27, 17–20 (2001).

  22. 22.

    Njor, S. H., Olsen, A. H., Schwartz, W., Vejborg, I. & Lynge, E. Predicting the risk of a false-positive test for women following a mammography screening programme. J. Med. Screen. 14, 94–97 (2007).

  23. 23.

    Hubbard, R. A., Miglioretti, D. L. & Smith, R. A. Modelling the cumulative risk of a false-positive screening test. Stat. Methods Med. Res. 19, 429–449 (2010).

  24. 24.

    Domingo, L. et al. Cross-national comparison of screening mammography accuracy measures in U.S., Norway, and Spain. Eur. Radiol. 26, 2520–2528 (2016).

  25. 25.

    Hofvind, S. et al. Interval breast cancer rates and histopathologic tumor characteristics after false-positive findings at mammography in a population-based screening program. Radiology 287, 58–67 (2018).

  26. 26.

    Castells, X. et al. Breast cancer risk after diagnosis by screening mammography of nonproliferative or proliferative benign breast disease: a study from a population-based screening program. Breast Cancer Res. Treat. 149, 237–244 (2015).

  27. 27.

    Hartmann, L. C. et al. Benign breast disease and the risk of breast cancer. N. Engl. J. Med. 353, 229–237 (2005).

  28. 28.

    Tice, J. A. et al. Benign breast disease, mammographic breast density, and the risk of breast cancer. J. Natl Cancer Inst. 105, 1043–1049 (2013).

  29. 29.

    Elmore, J. G. et al. International variation in screening mammography interpretations in community-based programs. J. Natl Cancer Inst. 95, 1384–1393 (2003).

  30. 30.

    Hofvind, S., Geller, B. M., Skelly, J. & Vacek, P. M. Sensitivity and specificity of mammographic screening as practised in Vermont and Norway. Br. J. Radiol. 85, e1226–e1232 (2012).

  31. 31.

    Smith-Bindman, R., Ballard-Barbash, R., Miglioretti, D. L., Patnick, J. & Kerlikowske, K. Comparing the performance of mammography screening in the USA and the UK. J. Med. Screen. 12, 50–54 (2005).

  32. 32.

    Boyd, N. F., Lockwood, G. A., Byng, J. W., Tritchler, D. L. & Yaffe, M. J. Mammographic densities and breast cancer risk. Cancer Epidemiol. Biomark. Prev. 7, 1133–1144 (1998).

  33. 33.

    Wolfe, J. N., Saftlas, A. F. & Salane, M. Mammographic parenchymal patterns and quantitative evaluation of mammographic densities: a case-control study. Am. J. Roentgenol. 148, 1087–1092 (1987).

  34. 34.

    McCormack, V. A. & dos Santos Silva, I. Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol. Biomark. Prev. 15, 1159–1169 (2006).

  35. 35.

    Nelson, H. D., O’Meara, E. S., Kerlikowske, K., Balch, S. & Miglioretti, D. Factors associated with rates of false-positive and false-negative results from digital mammography screening: an analysis of registry data. Ann. Intern. Med. 164, 226–235 (2016).

Download references


The authors would like to thank the Benign Lesion (BELE) Study Group (Spain); Walter Schwartz, Mammography Screening Clinic, University Hospital Odense, Denmark; Ilse Vejborg, Diagnostic Imaging Centre, Copenhagen University Hospital, Copenhagen, Denmark; the staff at the breast centres at BreastScreen Norway. This work had no specific funding source.

Author contributions

M.R., S.H., M.vE., and X.C. conceived the study and participated in its design. M.R., S.H., and M.vE. collected and checked the information recorded by the screening centres, and performed the extraction and validation of their data. M.R. merged and structured the analysis database, and performed the statistical analysis. The results were circulated and commented on by all the authors. M.R. drafted the first version, and it was critically reviewed by M.vE., S.H., and X.C. All authors read and approved the final manuscript.

Author information


  1. Department of Epidemiology and Evaluation, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain

    • Marta Román
    •  & Xavier Castells
  2. Network on Health Services in Chronic Diseases (REDISSEC), Barcelona, Spain

    • Marta Román
    •  & Xavier Castells
  3. Department of Screening, Cancer Registry of Norway, Oslo, Norway

    • Solveig Hofvind
  4. Oslo and Akershus University College of Applied Sciences, Faculty of Health Science, Oslo, Norway

    • Solveig Hofvind
  5. Department of Public Health, University of Copenhagen, Copenhagen, Denmark

    • My von Euler-Chelpin


  1. Search for Marta Román in:

  2. Search for Solveig Hofvind in:

  3. Search for My von Euler-Chelpin in:

  4. Search for Xavier Castells in:

Ethics approval and consent to participate

Data on screening results in Copenhagen were retrieved from the Copenhagen Mammography Register. Cancer Data on breast cancers were supplied by the Danish Cancer Registry and the Danish Breast Cancer Cooperative Group. Approval for data analysis was granted by the Danish Data Inspection Agency. Data from Norway was provided by the Cancer Registry of Norway. Collection of screening data follows the regulations of the institution and no ethical committee approval was necessary since all data used were anonymised. Screening data from Spain were obtained from the databases of the screening centres. The Review Boards of the institutions that provided data gave approval for data analyses.

Competing interests

The authors declare no competing interests.


This work is published under the standard license to publish agreement. After 12 months the work will become freely available and the license terms will switch to a Creative Commons Attribution 4.0 International (CC BY 4.0).

Corresponding author

Correspondence to Marta Román.

Supplementary information

About this article

Publication history





Issue Date


Further reading