Original Investigation| Volume 29, SUPPLEMENT 1, S180-S191, January 2022

True and Missed Interval Cancer in Organized Mammographic Screening: A Retrospective Review Study of Diagnostic and Prior Screening Mammograms

Published:April 26, 2021DOI:

      Rationale and Objectives

      To explore radiological aspects of interval breast cancer in a population-based screening program.

      Materials and Methods

      We performed a consensus-based informed review of mammograms from diagnosis and prior screening from women diagnosed with interval cancer 2004-2016 in BreastScreen Norway. Cases were classified as true (no findings on prior screening mammograms), occult (no findings at screening or diagnosis), minimal signs (minor/non-specific findings) and missed (obvious findings). We analyzed mammographic findings, density, time since prior screening, and histopathological characteristics between the classification groups.


      The study included 1010 interval cancer cases. Mean age at diagnosis was 61 years (SD = 6), mean time between screening and diagnosis 14 months (SD = 7). A total of 48% (479/1010) were classified as true or occult, 28% (285/1010) as minimal signs and 24% (246/1010) as missed. We observed no differences in mammographic density between the groups, except from a higher percentage of dense breasts in women with occult cancer. Among cancers classified as missed, about 1/3 were masses and 1/3 asymmetries at prior screening. True interval cancers were diagnosed later in the screening interval than the other classification categories. No differences in histopathological characteristics were observed between true, minimal signs and missed cases.


      In an informed review, 24% of the interval cancers were classified as missed based on visibility and mammographic findings on prior screening mammograms. Three out of four true interval cancers were diagnosed in the second year of the screening interval. We observed no statistical differences in histopathological characteristics between true and missed interval cancers.

      Key Words


      BI-RADS (Breast Imaging Reporting and Data System), CI (Confidence interval), DBT (Digital breast tomosynthesis), DM (Standard Digital mammography), IQR (Interquartile range), NST (Invasive carcinoma no special type), PACS (Picture archiving and communication system), SD (Standard deviation)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Academic Radiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Perry N
        • Broeders M
        • de Wolf C
        • et al.
        European guidelines for quality assurance in breast cancer screening and diagnosis.
        European Communities, Brussels, Belgium2006
        • Houssami N
        • Hunter K.
        The epidemiology, radiology and biological characteristics of interval breast cancers in population mammography screening.
        NPJ Breast Cancer. 2017; 3: 12
        • Messinger J
        • Crawford S
        • Roland L
        • et al.
        Review of subtypes of interval breast cancers with discussion of radiographic findings.
        Curr Probl Diagn Radiol. 2019; 48: 592-598
        • Houssami N
        • Irwig L
        • Ciatto S.
        Radiological surveillance of interval breast cancers in screening programmes.
        Lancet Oncol. 2006; 7: 259-265
        • Bellio G
        • Marion R
        • Giudici F
        • et al.
        Interval breast cancer versus screen-detected cancer—comparison of clinicopathologic characteristics in a single-center analysis.
        Clin Breast Cancer. 2017; 17: 564-571
        • Cheasley D
        • Li N
        • Rowley SM
        • et al.
        Molecular comparison of interval and screen-detected breast cancers.
        J Pathol. 2019; 248: 243-252
        • Gilliland FD
        • Joste N
        • Stauber PM
        • et al.
        Biologic characteristics of interval and screen-detected breast cancers.
        J Natl Cancer Inst. 2000; 92: 743-749
        • Wishart GC
        • Greenberg DC
        • Britton PD
        • et al.
        Screen-detected vs symptomatic breast cancer—is improved survival due to stage migration alone?.
        Br J Cancer. 2008; 98: 1741-1744
        • Carbonaro LA
        • Azzarone A
        • Paskeh BB
        • et al.
        Interval breast cancers—absolute and proportional incidence and blinded review in a community mammographic screening program.
        Eur J Radiol. 2014; 83: e84-e91
        • Tornberg S
        • Kemetli L
        • Ascunce N
        • et al.
        A pooled analysis of interval cancer rates in six European countries.
        Eur J Cancer Prev. 2010; 19: 87-93
        • Andersen SB
        • Tornberg S
        • Lynge E
        • et al.
        A simple way to measure the burden of interval cancers in breast cancer screening.
        BMC Cancer. 2014; 14: 782
        • Bulliard JL
        • Sasieni P
        • Klabunde C
        • et al.
        Methodological issues in international comparison of interval breast cancers.
        Int J Cancer. 2006; 119: 1158-1163
      1. Hofvind S, Tsuruda K, Mangerud G, Ertzaas A, Holen A, Pedersen K, et al. The Norwegian Breast Cancer Screening Program, 1996-2016: Celebrating 20 years of organised mammographic screening. Cancer in Norway 2016 - Cancer incidence, mortality, survival and prevalence in Norway: Cancer Registry of Norway; 2017

        • Boyd NF
        • Huszti E
        • Melnichouk O
        • et al.
        Mammographic features associated with interval breast cancers in screening programs.
        Breast Cancer Res. 2014; 16: 417
        • Domingo L
        • Salas D
        • Zubizarreta R
        • et al.
        Tumor phenotype and breast density in distinct categories of interval cancer: results of population-based mammography screening in Spain.
        Breast Cancer Res. 2014; 16: R3
        • MacInnes EG
        • Duffy SW
        • Simpson JA
        • et al.
        Radiological audit of interval breast cancers: Estimation of tumor growth rates.
        Breast. 2020; 51: 114-119
      2. Ministry of Health and Care Services, Forskrift om innsamling og behandling av helseopplysninger i Kreftregisteret (The Cancer Registry Regulation), (2001).

      3. Hoff SR, Myklebust TA, Lee CI, Hofvind S. Influence of Mammography Volume on Radiologists' Performance: Results from BreastScreen Norway. Radiology. 2019;292(2):289-96.

      4. Hovda T, Tsuruda K, Hoff SR, Sahlberg KK, Hofvind S. Radiological review of prior screening mammograms of screen-detected breast cancer. Eur Radiol. 2021;31(4):2568-79

        • Sickles E
        • D'Orsi CJ
        • Bassett LW
        • et al.
        ACR BI-RADS Mammography.
        ACR BI-RADS Atlas, Breast Imaging Reporting and Data System. American College of Radiology, Reston, VA2013
        • Hofvind S
        • Geller B
        • Skaane P.
        Mammographic features and histopathological findings of interval breast cancers.
        Acta radiologica (Stockholm, Sweden: 1987). 2008; 49: 975-981
        • Hoff SR
        • Samset JH
        • Abrahamsen AL
        • et al.
        Missed and true interval and screen-detected breast cancers in a population based screening program.
        Acad Radiol. 2011; 18: 454-460
        • Weber RJ
        • van Bommel RM
        • Louwman MW
        • et al.
        Characteristics and prognosis of interval cancers after biennial screen-film or full-field digital screening mammography.
        Breast Cancer Res Treat. 2016; 158: 471-483
        • Gordon PB
        • Borugian MJ
        • Warren Burhenne LJ
        A true screening environment for review of interval breast cancers—pilot study to reduce bias.
        Radiology. 2007; 245: 411-415
        • Hofvind S
        • Skaane P
        • Vitak B
        • et al.
        Influence of review design on percentages of missed interval breast cancers: retrospective study of interval cancers in a population-based screening program.
        Radiology. 2005; 237: 437-443
        • Ciatto S
        • Catarzi S
        • Lamberini MP
        • et al.
        Interval breast cancers in screening: the effect of mammography review method on classification.
        Breast. 2007; 16: 646-652
        • Moberg K
        • Grundstrom H
        • Tornberg S
        • et al.
        Two models for radiological reviewing of interval cancers.
        J Med Screen. 1999; 6: 35-39
        • Lamb LR
        • Mohallem Fonseca M
        • Verma R
        • et al.
        Missed breast cancer—effects of subconscious bias and lesion characteristics.
        Radiographics. 2020; 40: 941-960
        • Roberts-Klein S
        • Iuanow E
        • Slanetz PJ.
        Avoiding pitfalls in mammographic interpretation.
        Can Assoc Radiol J. 2011; 62: 50-59
        • Boyd NF
        • Guo H
        • Martin LJ
        • et al.
        Mammographic density and the risk and detection of breast cancer.
        N Engl J Med. 2007; 356: 227-236
        • Evans AJ
        • Kutt E
        • Record C
        • et al.
        Radiological and pathological findings of interval cancers in a multi-centre, randomized, controlled trial of mammographic screening in women from age 40-41 years.
        Clin Radiol. 2007; 62: 348-352
        • Moshina N.
        Comparing screening outcomes for digital breast tomosynthesis and digital mammography by automated breast density in a randomized controlled trial: Results from the To-Be trial Radiology.
        • Skaane P
        • Bandos AI
        • Niklason LT
        • et al.
        Digital mammography versus digital mammography plus tomosynthesis in breast cancer screening—the oslo tomosynthesis screening trial.
        Radiology. 2019; 291: 23-30
        • Hofvind S
        • Hovda T
        • Holen AS
        • et al.
        Digital breast tomosynthesis and synthetic 2d mammography versus digital mammography—evaluation in a population-based screening program.
        Radiology. 2018; 287: 787-794
        • Zackrisson S
        • Lang K
        • Rosso A
        • et al.
        One-view breast tomosynthesis versus two-view mammography in the Malmo Breast Tomosynthesis Screening Trial (MBTST): a prospective, population-based, diagnostic accuracy study.
        Lancet Oncol. 2018; 19: 1493-1503
        • Bernardi D
        • Macaskill P
        • Pellegrini M
        • et al.
        Breast cancer screening with tomosynthesis (3D mammography) with acquired or synthetic 2D mammography compared with 2D mammography alone (STORM-2) —a population-based prospective study.
        Lancet Oncol. 2016; 17: 1105-1113
        • Marinovich ML
        • Hunter KE
        • Macaskill P
        • et al.
        Breast cancer screening using tomosynthesis or mammography: a meta-analysis of cancer detection and recall.
        J Natl Cancer Inst. 2018; 110: 942-949
        • Comstock CE
        • Gatsonis C
        • Newstead GM
        • et al.
        Comparison of abbreviated breast MRI vs digital breast tomosynthesis for breast cancer detection among women with dense breasts undergoing screening.
        JAMA. 2020; 323: 746-756
        • Rella R
        • Belli P
        • Giuliani M
        • et al.
        Automated breast ultrasonography (abus) in the screening and diagnostic setting—indications and practical use.
        Acad Radiol. 2018; 25: 1457-1470
        • Bakker MF
        • de Lange SV
        • Pijnappel RM
        • et al.
        Supplemental MRI screening for women with extremely dense breast tissue.
        N Engl J Med. 2019; 381: 2091-2102
        • National Health Service Breast Screening Programme
        National collation of breast interval cancer data. NHSBSP Occational Report 12/03.
      5. Hofvind S, Vacek PM, Skelly J, Weaver DL, Geller BM. Comparing screening mammography for early breast cancer detection in Vermont and Norway. J Natl Cancer Inst. 2008;100(15):1082-91.

      6. Hofvind S, Yankaskas BC, Bulliard JL, Klabunde CN, Fracheboud J. Comparing interval breast cancer rates in Norway and North Carolina: results and challenges. J Med Screen. 2009;16(3):131-9.

      7. ECIBC. Recommendations from the European Breast Cancer Guidelines [updated 28/05/2020. Available from: Accessed June 2020.

        • Arleo EK
        • Hendrick RE
        • Helvie MA
        • et al.
        Comparison of recommendations for screening mammography using CISNET models.
        Cancer. 2017; 123: 3673-3680
        • Porter GJ
        • Evans AJ
        • Burrell HC
        • et al.
        Interval breast cancers: prognostic features and survival by subtype and time since screening.
        J Med Screen. 2006; 13: 115-122
        • Meshkat B
        • Prichard RS
        • Al-Hilli Z
        • et al.
        A comparison of clinical-pathological characteristics between symptomatic and interval breast cancer.
        Breast. 2015; 24: 278-282
        • Bare M
        • Tora N
        • Salas D
        • et al.
        Mammographic and clinical characteristics of different phenotypes of screen-detected and interval breast cancers in a nationwide screening program.
        Breast Cancer Res Treat. 2015; 154: 403-415
        • Brennan PC
        • Ganesan A
        • Eckstein MP
        • et al.
        Benefits of independent double reading in digital mammography—a theoretical evaluation of all possible pairing methodologies.
        Acad Radiol. 2019; 26: 717-723
        • Hofvind S
        • Geller BM
        • Rosenberg RD
        • et al.
        Screening-detected breast cancers: discordant independent double reading in a population-based screening program.
        Radiology. 2009; 253: 652-660
        • Rodriguez-Ruiz A
        • Krupinski E
        • Mordang JJ
        • et al.
        Detection of breast cancer with mammography—effect of an artificial intelligence support system.
        Radiology. 2019; 290: 305-314
        • Lång K
        • Hofvind S
        • Rodriguez Ruiz A
        • et al.
        Can artificial intelligence reduce the interval cancer rate in mammography screening?.
        Eur Radiol. 2020; (Online ahead of print)
        • Sechopoulos I
        • Teuwen J
        • Mann R.
        Artificial intelligence for breast cancer detection in mammography and digital breast tomosynthesis—state of the art.
        Semin Cancer Biol. 2020; (Online ahead of print)