Accuracy of screening women at familial risk of breast cancer without a known gene mutation: Individual patient data meta-analysis

Published:September 05, 2017DOI:


      • In women at familial risk and no known mutations, we estimate a breast cancer (BC) rate of 12 per 1000 woman-years.
      • BC rate increased from 5.1 per 1000 in women <40 years to 21 per 1000 in women >50 years.
      • Mammography sensitivity ranged from 51% in women <40 to 67% in women ≥50 years.
      • Adjunct magnetic resonance imaging increased sensitivity by 43% but decreased specificity by 15%.



      Women with a strong family history of breast cancer (BC) and without a known gene mutation have an increased risk of developing BC. We aimed to investigate the accuracy of screening using annual mammography with or without magnetic resonance imaging (MRI) for these women outside the general population screening program.


      An individual patient data (IPD) meta-analysis was conducted using IPD from six prospective screening trials that had included women at increased risk for BC: only women with a strong familial risk for BC and without a known gene mutation were included in this analysis. A generalised linear mixed model was applied to estimate and compare screening accuracy (sensitivity, specificity and predictive values) for annual mammography with or without MRI.


      There were 2226 women (median age: 41 years, interquartile range 35–47) with 7478 woman-years of follow-up, with a BC rate of 12 (95% confidence interval 9.3–14) in 1000 woman-years. Mammography screening had a sensitivity of 55% (standard error of mean [SE] 7.0) and a specificity of 94% (SE 1.3). Screening with MRI alone had a sensitivity of 89% (SE 4.6) and a specificity of 83% (SE 2.8). Adding MRI to mammography increased sensitivity to 98% (SE 1.8, P < 0.01 compared to mammography alone) but lowered specificity to 79% (SE 2.7, P < 0.01 compared with mammography alone).


      In this population of women with strong familial BC risk but without a known gene mutation, in whom BC incidence was high both before and after age 50, adding MRI to mammography substantially increased screening sensitivity but also decreased its specificity.


      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 European Journal of Cancer
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Lynch H.T.
        • Silva E.
        • Snyder C.
        • Lynch J.F.
        Hereditary breast cancer: part I. Diagnosing hereditary breast cancer syndromes.
        Breast J. 2008; 14: 3-13
        • Claus E.B.
        • Risch N.
        • Thompson W.D.
        Autosomal dominant inheritance of early-onset breast cancer. Implications for risk prediction.
        Cancer. 1994; 73: 643-651
        • van Asperen C.J.
        • Jonker M.A.
        • Jacobi C.E.
        • van Diemen-Homan J.E.
        • Bakker E.
        • Breuning M.H.
        • et al.
        Risk estimation for healthy women from breast cancer families: new insights and new strategies.
        Cancer Epidemiol Biomarkers Prev. 2004; 13: 87-93
        • National Institute for Health and Care Excellence
        Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer.
        Date accessed: May 19, 2017
        • Integraal Kankercentrum Nederland
        Richtlijn mammacarcinoom (Breast Cancer National Guideline).
        Date accessed: May 19, 2017
        • Kuhl C.
        • Weigel S.
        • Schrading S.
        • Arand B.
        • Bieling H.
        • König R.
        • et al.
        Prospective multicenter cohort study to refine management recommendations for women at elevated familial risk of breast cancer: the EVA trial.
        J Clin Oncol. 2010; 28: 1450-1457
        • Kuhl C.K.
        • Schrading S.
        • Leutner C.C.
        • Morakkabati-Spitz N.
        • Wardelmann E.
        • Fimmers R.
        • et al.
        Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer.
        J Clin Oncol. 2005; 23: 8469-8476
        • Leach M.O.
        • Boggis C.R.
        • Dixon A.K.
        • Easton D.F.
        • Eeles R.A.
        • Evans D.G.
        • et al.
        Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS).
        Lancet. 2005; 365: 1769-1778
        • Lehman C.D.
        • Blume J.D.
        • Weatherall P.
        • Thickman D.
        • Hylton N.
        • Warner E.
        • et al.
        Screening women at high risk for breast cancer with mammography and magnetic resonance imaging.
        Cancer. 2005; 103: 1898-1905
        • Lehman C.D.
        • Isaacs C.
        • Schnall M.D.
        • Pisano E.D.
        • Ascher S.M.
        • Weatherall P.T.
        • et al.
        Cancer yield of mammography, MR, and US in high-risk women: prospective multi-institution breast cancer screening study.
        Radiology. 2007; 244: 381-388
        • Riedl C.C.
        • Luft N.
        • Bernhart C.
        • Weber M.
        • Bernathova M.
        • Tea M.K.
        • et al.
        Triple-modality screening trial for familial breast cancer underlines the importance of magnetic resonance imaging and questions the role of mammography and ultrasound regardless of patient mutation status, age, and breast density.
        J Clin Oncol. 2015; 33: 1128-1135
        • Rijnsburger A.J.
        • Obdeijn I.M.
        • Kaas R.
        • Tilanus-Linthorst M.M.
        • Boetes C.
        • Loo C.E.
        • et al.
        BRCA1-associated breast cancers present differently from BRCA2-associated and familial cases: long-term follow-up of the Dutch MRISC screening study.
        J Clin Oncol. 2010; 28: 5265-5273
        • Sardanelli F.
        • Podo F.
        • Santoro F.
        • Manoukian S.
        • Bergonzi S.
        • Trecate G.
        • et al.
        Multicenter surveillance of women at high genetic breast cancer risk using mammography, ultrasonography, and contrast-enhanced magnetic resonance imaging (the high breast cancer risk Italian 1 study): final results.
        Investig Radiol. 2011; 46: 94-105
        • Warner E.
        • Plewes D.B.
        • Shumak R.S.
        • Catzavelos G.C.
        • Di Prospero L.S.
        • Yaffe M.J.
        • et al.
        Comparison of breast magnetic resonance imaging, mammography, and ultrasound for surveillance of women at high risk for hereditary breast cancer.
        J Clin Oncol. 2001; 19: 3524-3531
        • Trop I.
        • Lalonde L.
        • Mayrand M.H.
        • David J.
        • Larouche N.
        • Provencher D.
        Multimodality breast cancer screening in women with a familial or genetic predisposition.
        Curr Oncol. 2010; 17: 28-36
        • Phi X.A.
        • Saadatmand S.
        • De Bock G.H.
        • Warner E.
        • Sardanelli F.
        • Leach M.O.
        • et al.
        Contribution of mammography to MRI screening in BRCA mutation carriers by BRCA status and age: individual patient data meta-analysis.
        Br J Cancer. 2016; 114: 631-637
        • Phi X.A.
        • Houssami N.
        • Obdeijn I.
        • Warner E.
        • Sardanelli F.
        • Leach M.O.
        • et al.
        Magnetic resonance imaging improves breast screening sensitivity in BRCA mutation carriers age >/= 50 Years: evidence from an individual patient data meta-analysis.
        J Clin Oncol. 2014; 33: 349-356
        • Weinstein S.P.
        • Localio A.R.
        • Conant E.F.
        • Rosen M.
        • Thomas K.M.
        • Schnall M.D.
        Multimodality screening of high-risk women: a prospective cohort study.
        J Clin Oncol. 2009; 27: 6124-6128
        • Berg W.A.
        • Blume J.D.
        • Cormack J.B.
        • Mendelson E.B.
        • Lehrer D.
        • Böhm-Vélez M.
        • et al.
        Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer.
        JAMA. 2008; 299: 2151-2163
        • Narayan A.K.
        • Visvanathan K.
        • Harvey S.C.
        Comparative effectiveness of breast MRI and mammography in screening young women with elevated risk of developing breast cancer: a retrospective cohort study.
        Breast Cancer Res Treat. 2016; 158: 583-589
        • Pinker K.
        • Helbich T.H.
        • Morris E.A.
        The potential of multiparametric MRI of the breast.
        Br J Radiol. 2017; 90: 20160715
        • Bickelhaupt S.
        • Laun F.B.
        • Tesdorff J.
        • Lederer W.
        • Daniel H.
        • Stieber A.
        • et al.
        Fast and noninvasive characterization of suspicious lesions detected at breast cancer X-ray screening: capability of diffusion-weighted MR imaging with MIPs.
        Radiology. 2016; 278: 689-697
        • American College of Radiology
        ACR BI-RADS® Atlas, breast imaging reporting and data system.
        (Reston, VA)2013
        • Ciatto S.
        • Houssami N.
        • Bernardi D.
        • Caumo F.
        • Pellegrini M.
        • Brunelli S.
        • et al.
        Integration of 3D digital mammography with tomosynthesis for population breast-cancer screening (STORM): a prospective comparison study.
        Lancet Oncol. 2013; 14: 583-589
        • Bernardi D.
        • Macaskill P.
        • Pellegrini M.
        • Valentini M.
        • Fantò C.
        • Ostillio L.
        • 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
        • Arnold M.
        • Karim-Kos H.E.
        • Coebergh J.W.
        • Byrnes G.
        • Antilla A.
        • Ferlay J.
        • et al.
        Recent trends in incidence of five common cancers in 26 European countries since 1988: analysis of the European Cancer Observatory.
        Eur J Cancer. 2015; 51: 1164-1187
        • Canadian Breast Cancer Foundation
        Breast cancer in Canadian, 2016.