Original Investigation|Articles in Press

Interval Breast Cancers Versus Screen Detected Breast Cancers: A Retrospective Cohort Study

Published:February 03, 2023DOI:

      Rationale and Objective

      Mammographic screening detects most breast cancers but there are still women diagnosed with breast cancer between annual mammograms. We aim to identify features that differentiate screen detected breast cancers from interval breast cancer.

      Materials and Methods

      All screening mammograms (n = 211,517) performed 7/1/2013-6/30/2020 at our institution were reviewed. Patients with breast cancer diagnosed within one year of screening were included and divided into two distinct groups: screen detected cancer group and interval cancer group. Characteristics in these groups were compared using the chi square test, fisher test, and student's T test.


      A total of 1,232 patients were included (mean age 64 +/- 11). Sensitivity of screening mammography was 92% (1,136 screen detected cancers, 96 interval cancers).
      Patient age, race, and personal history of breast cancer were similar between the groups (p > 0.05). Patients with interval cancers more often had dense breast tissue (75/96 = 78% versus 694/1136 = 61%, p < 0.001).
      Compared to screen detected cancers, interval cancers were more often primary tumor stage two or higher (41/96 = 43% versus 139/1136 = 12%, p < 0.001) and regional lymph node stage one or higher (21/96 = 22% versus 132/1136 = 12%, p = 0.003). Interval cancers were more often triple negative (16/77 = 21% versus [48/813 = 6%], p < 0.001) with high Ki67 proliferation indices (28/45 = 62% versus 188/492 = 38%, p = 0.002).


      Mammographic screening had high sensitivity for breast cancer detection (92%). Interval cancers were associated with dense breast tissue and had higher stage with less favorable molecular features compared to screen detected cancers.

      Key Words


      DBT (Digital breast tomosynthesis), FFDM (Full field digital mammography), BI-RADS (Breast Imaging Reporting and Data Systems), ER (Estrogen receptor), PR (Progesterone receptor), HER-2 (Human epidermal growth factor receptor)
      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


        • Henderson LM
        • O'Meara ES
        • Braithwaite D
        • et al.
        Performance of digital screening mammography among older women in the United States.
        Cancer. 2015; 121: 1379-1386
        • Carney PA
        • Miglioretti DL
        • Yankaskas BC
        • et al.
        Individual and combined effects of age, breast density, and hormone replacement therapy use on the accuracy of screening mammography background: the relationships among breast density.
        Ann Intern Med. 2003; 138 (Available at) (Accessed December 22, 2020): 168-175
        • Bird RE
        • Wallace TW
        • Yankaskas BC.
        Analysis of cancers missed at screening mammography.
        Radiology. 1992; 184: 613-617
        • Nelson HD
        • O'Meara ES
        • Kerlikowske K
        • et al.
        Factors associated with rates of false-positive and false-negative results from digital mammography screening: an analysis of registry data.
        Ann Intern Med. 2016; 164: 226-235
      1. Durand MA, Friedewald SM, Plecha DM, et al. False-negative rates of breast cancer screening with and without digital breast tomosynthesis. Radiology. 292, 2. doi:10.1148/radiol.2020202858.

        • Rosenberg RD
        • Hunt WC
        • Williamson MR
        • et al.
        Effects of age, breast density, ethnicity, and estrogen replacement therapy on screening mammographic sensitivity and cancer stage at diagnosis: review of 183,134 screening mammograms in Albuquerque, New Mexico.
        Radiology. 1998; 209: 511-518
        • Porter PL
        • El-Bastawissi AY
        • Mandelson MT
        • et al.
        Breast tumor characteristics as predictors of mammographic detection: comparison of interval- and screen-detected cancers.
        J Natl Cancer Inst. 1999; 91: 2020-2028
        • 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
        • Domingo L
        • Sala M
        • Servitja S
        • et al.
        Phenotypic characterization and risk factors for interval breast cancers in a population-based breast cancer screening program in Barcelona, Spain.
        Cancer Causes Control. 2010; 21: 1155-1164
        • Ciatto S
        • Visioli C
        • Paci E
        • et al.
        Breast density as a determinant of interval cancer at mammographic screening.
        Br J Cancer. 2004; 90: 393-396
        • Nguyen TL
        • Li S
        • Dite GS
        • et al.
        Interval breast cancer risk associations with breast density, family history and breast tissue aging.
        Int J Cancer. 2020; 147: 375
        • Wanders JOP
        • Holland K
        • Karssemeijer N
        • et al.
        The effect of volumetric breast density on the risk of screen-detected and interval breast cancers: a cohort study.
        Breast Cancer Res. 2017; 19: 95-103
        • Boyd NF
        • Lockwood GA
        • Martin LJ
        • et al.
        Mammographic densities and breast cancer risk.
        Breast Dis. 1998; 10: 113-126
        • McCormack VA
        • Dos Santos Silva I.
        Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis.
        Cancer Epidemiol Biomarkers Prev. 2006; 15: 1159-1169
        • Boyd NF
        • Martin LJ
        • Yaffe MJ
        • et al.
        Mammographic density and breast cancer risk: current understanding and future prospects.
        Breast Cancer Res. 2011; 13: 479-502
        • Freer PE.
        Mammographic breast density: impact on breast cancer risk and implications for screening.
        Radiographics. 2015; 35: 302-315
        • Hunter A.
        Mammographic density: the risk and detection of breast caner.
        J BioLaw Bus. 2007; 10: 60-61
        • McCormack V
        • I dos SS-CEB
        Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis.
        AACR. 2006; 15: 1159-1169
        • Sprague BL
        • Gangnon RE
        • Burt V
        • et al.
        Prevalence of mammographically dense breasts in the United States.
        JNCI J Natl Cancer Inst. 2014; 106
        • Beral V
        • Bull D
        • Doll R
        • et al.
        Familial breast cancer: collaborative reanalysis of individual data from 52 epidemiological studies including 58,209 women with breast cancer and 101,986 women without the disease.
        Lancet (London, England. 2001; 358: 1389-1399
        • Hofvind S
        • Moshina N
        • Holen ÅS
        • et al.
        Interval and subsequent round breast cancer in a randomized controlled trial comparing digital breast tomosynthesis and digital mammography screening.
        Radiology. 2021; 300: 66-76
        • Johnson K
        • Lång K
        • Ikeda DM
        • et al.
        Interval breast cancer rates and tumor characteristics in the prospective population-based malmö breast tomosynthesis screening trial.
        Radiology. 2021; 299: 559-567
        • McCarthy AM
        • Barlow WE
        • Conant EF
        • et al.
        Breast cancer with a poor prognosis diagnosed after screening mammography with negative results.
        JAMA Oncol. 2018; 4: 998-1001
        • Kirsh VA
        • Chiarelli AM
        • Edwards SA
        • et al.
        Tumor characteristics associated with mammographic detection of breast cancer in the ontario breast screening program.
        J Natl Cancer Inst. 2011; 103: 942-950
        • Niraula S
        • Biswanger N
        • Hu PZ
        • et al.
        Incidence, characteristics, and outcomes of interval breast cancers compared with screening-detected breast cancers.
        JAMA Netw Open. 2020; 3
      2. SEER*Explorer Application. Available at: Accessed December 30, 2020.

        • Mainiero MB
        • Lourenco A
        • Mahoney MC
        • et al.
        ACR appropriateness criteria breast cancer screening.
        J Am Coll Radiol. 2016; 13: R45-R49
      3. Miles R, Wan F, Onega TL, et al. Underutilization of supplemental magnetic resonance imaging screening among patients at high breast cancer risk. Available at: 2018;27(6):748-754. doi:10.1089/JWH.2017.6623

        • Kuhl CK
        • Schrading S
        • Strobel K
        • et al.
        Abbreviated breast magnetic resonance imaging (MRI): first postcontrast subtracted images and maximum-intensity projection - a novel approach to breast cancer screening with MRI.
        J Clin Oncol. 2014; 32: 2304-2310
        • 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 - J Am Med Assoc. 2020; 323: 746-756
        • Choi BH
        • Choi N
        • Kim MY
        • et al.
        Usefulness of abbreviated breast MRI screening for women with a history of breast cancer surgery.
        Breast Cancer Res Treat. 2018; 167: 495-502
        • Wang J
        • Greuter MJW
        • Vermeulen KM
        • et al.
        Cost-effectiveness of abbreviated-protocol MRI screening for women with mammographically dense breasts in a national breast cancer screening program.
        The Breast. 2022; 61: 58-65
        • Geuzinge HA
        • Obdeijn IM
        • Rutgers EJT
        • et al.
        Cost-effectiveness of breast cancer screening with magnetic resonance imaging for women at familial risk.
        JAMA Oncol. 2020; 6: 1381-1389
        • Mann RM
        • Hooley R
        • Barr RG
        • et al.
        Novel approaches to screening for breast cancer.
        Radiology. 2020; 297: 266-285
        • Phallen J
        • Sausen M
        • Adleff V
        • et al.
        Direct detection of early-stage cancers using circulating tumor DNA.
        Sci Transl Med. 2017; 9
        • Cohen JD
        • Li L
        • Wang Y
        • et al.
        Detection and localization of surgically resectable cancers with a multi-analyte blood test.
        Science. 2018; 359: 926-930