Assessment of false-negative cases of breast MR imaging in women with a familial or genetic predisposition

  • Inge-Marie A. Obdeijn
  • Claudette E. Loo
  • Adriana J. Rijnsburger
  • Martin N. J. M. Wasser
  • Elisabeth Bergers
  • Theo Kok
  • Jan G. M. Klijn
  • Carla Boetes
Clinical trial


In order to assess the characteristics of malignant breast lesions those were not detected during screening by MR imaging. In the Dutch MRI screening study (MRISC), a non-randomized prospective multicenter study, women with high familial risk or a genetic predisposition for breast cancer were screened once a year by mammography and MRI and every 6 months with a clinical breast examination (CBE). The false-negative MR examinations were subject of this study and were retrospectively reviewed by two experienced radiologists. From November 1999 until March 2006, 2,157 women were eligible for study analyses. Ninety-seven malignant breast tumors were detected, including 19 DCIS (20%). In 22 patients with a malignant lesion, the MRI was assessed as BI-RADS 1 or 2. One patient was excluded because the examinations were not available for review. Forty-three percent (9/21) of the false-negative MR cases concerned pure ductal carcinoma in situ (DCIS) or DCIS with invasive foci, in eight of them no enhancement was seen at the review. In six patients the features of malignancy were missed or misinterpreted. Small lesion size (n = 3), extensive diffuse contrast enhancement of the breast parenchyma (n = 2), and a technically inadequate examination (n = 1) were other causes of the missed diagnosis. A major part of the false-negative MR diagnoses concerned non-enhancing DCIS, underlining the necessity of screening not only with MRI but also with mammography. Improvement of MRI scanning protocols may increase the detection rate of DCIS. The missed and misinterpreted cases are reflecting the learning curve of a multicenter study.


Breast cancer MRI Screening Hereditary 


  1. 1.
    Kiemeney LA, Lemmers FA, Verhoeven RH, Aben KK, Honing C, de Nooijer J, Peeters PH, Visser O, Vlems FA (2008) The risk of cancer in the Netherlands. Ned Tijdschr Geneeskd 152(41):2233–2436PubMedGoogle Scholar
  2. 2.
    Antoniou A, Pharoah PDP, Narod S, Risch HA, Eyfjord JE, Hopper JL (2003) Average risk of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am J Hum Genet 72:1117–1130PubMedCrossRefGoogle Scholar
  3. 3.
    Kolb TM, Lichy J, Newhouse JH (2002) Comparison of the performance of screening mammography, physical examination, and breast US and evaluation of factors that influence them: an analysis of 27,825 patient evaluation. Radiology 225(1):165–175PubMedCrossRefGoogle Scholar
  4. 4.
    Brekelmans CT, Seynave C, Bartels CC, Tilanus-Linthorst MM, Meijers-Heijboer EJ, Crepin CM, van Geel AA, Menke M, Verhoog LC, van den Ouweland A, Obdeijn IM, Klijn JG, Rotterdam committee for medical, genetic counselling (2001) Effectiveness of breast cancer surveillance in BRCA1/2 gene mutation carriers and women with high familial risk. J Clin Oncol 19(4):924–930PubMedGoogle Scholar
  5. 5.
    Tilanus-Linthorst M, Verhoog L, Obdeijn IM, Bartels K, Menke-Pluymers M, Eggermont A, Klijn J, Meijers-Heijboer H, van der Kwast T, Brekelmans C (2002) A BRCA1/2 mutation, high breast density and prominent pushing margins of a tumor independently contribute to a frequent false-negative mammography. Int J Cancer 102:91–95PubMedCrossRefGoogle Scholar
  6. 6.
    Lakhani SR, Jacquemier J, Sloane JP, Guterson BA, Anderson TJ, van de Vijver MJ, Farid LM, Venter D, Antoniou A, Storfer A, Smyth E, Steel M, Haites N, Scott RJ, Goldgar D, Neuhausen S, Daly PA et al (1998) Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations. J Natl Cancer Inst 90:1138–1145PubMedCrossRefGoogle Scholar
  7. 7.
    Komenaka IK, Ditkoff B-A, Joseph K-A, Russo D, Choroochurn P, Ward M, Horowitz E, El-Tamer MB, Schnabel FR (2004) The development of interval breast malignancies in patients with BRCA mutations. Cancer 100:2079–2083PubMedCrossRefGoogle Scholar
  8. 8.
    Harms SE, Flamig DP, Hesley KL, Meiches MD, Jensen RA, Evans WP, Savino DA, Wells RV (1993) MR imaging if the breast with rotating delivery of excitation off resonance: clinical experience with pathologic correlation. Radiology 187(2):493–501PubMedGoogle Scholar
  9. 9.
    Heywang-Kobrunner SH (1994) Contrast-enhanced magnetic resonance imaging of the breast. Invest Radiol 29:94–104PubMedCrossRefGoogle Scholar
  10. 10.
    Orel SG, Schnall MD (2001) MR Imaging of the breast for the detection, diagnosis, and staging of breast cancer. Radiology 220:13–30PubMedGoogle Scholar
  11. 11.
    Tilanus-Linthorst MMA, Obdeijn AIM, Bartels CCM, de Koning HJ, Oudkerk M (2000) First experiences in screening women at high risk for breast cancer with MR imaging. Breast Cancer Res Treat 63:53–60PubMedCrossRefGoogle Scholar
  12. 12.
    Kuhl CK, Schmutzler RK, Leutner CC, Kempe A, Wardelmann E, Hocke A, Maringa M, Pfeifer U, Krebs D, Schild HH (2000) Breast imaging screening in 192 women proved or suspected to be carriers of a breast cancer susceptibility gene: preliminary results. Radiology 215:267–279PubMedGoogle Scholar
  13. 13.
    Warner E, Plewes DB, Shumak RS, Catzavelos GC, Prospero Di LS, Yaffe MJ, Goel V, Ramsey E, Chart PL, Cole DCE, Taylor GA, Cutrara M, Samuels TH, Murphy JP, Narod SA (2001) Comparison of breast magnetic resonance imaging, mammography, and ultrasound for surveillance of women at high risk for hereditary breast cancer. J Clin Oncol 19:3524–3531PubMedGoogle Scholar
  14. 14.
    Podo E, Sardanelli F, Canese R, D’Agnolo, Natali PG, Crecco M, Grandinetti ML, Musumeci R, Trecate G, Bergonzi S, De Simone T, Pasisni B, Manuokian S, Spatti GB, Vergnaghi D, Morassut S, Panizza P, Del Maschio A (2002) The Italian multi-center project on evaluation of MRI and other imaging modalities in early detection of breast cancer in subjects at high genetic risk. J Exp Clin Cancer Res 21(Suppl 3):115–124PubMedGoogle Scholar
  15. 15.
    Kriege M, Brekelmans CTM, Boetes C, Besnard PE, Zonderland HM, Obdeijn IM, Manoliu RA, Kok T, Peterse H, Tilanus-linthorst MMA, Muller SA, Meijer S, Oosterwijk JC, Beex LVAM, Tollenaar RAEM, de Koning HJ, Rutgers EJT, Klijn JGM (2004) Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med 351(5):427–437PubMedCrossRefGoogle Scholar
  16. 16.
    Warner E, Plewes DB, Hill KA, Causer PA, Zubovits JT, Jong RA, Cutrara MR, DeBoer G, Yaffe MJ, Messner SJ, Meschino WS, Piron CA, Narod SA (2004) Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA 292:1317–1325PubMedCrossRefGoogle Scholar
  17. 17.
    MARIBS study group (2005) Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer; a prospective multicenter cohort study (MARIBS). Lancet 365:1769–1778CrossRefGoogle Scholar
  18. 18.
    Kuhl CK, Schrading S, Leutner CC, Morakkabati-Spitz N, Wardelmann E, Fimmers R, Kuhn, Schild HH (2005) Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk of breast cancer. J Clin Oncol 23:8469–8476PubMedCrossRefGoogle Scholar
  19. 19.
    Sardanelli F, Podo F, D’Agnolo G, Verdecchia A, Santaquilana M, Musumeci R, Trecate G, Manoukian S, Morassut S, de Giacomi C, Federico M, Cortesi L, Corcione S, Cirillo S, Marra V (2007) Multicenter comparative multimodality surveillance of women at genetic-familial high risk for breast cancer (HIBCRIT Study): interim results. Radiology 242:698–715PubMedCrossRefGoogle Scholar
  20. 20.
    Sardanelli F, Podo F (2007) Breast imaging in women at high risk of breast cancer. Is something changing in early breast cancer detection? Eur Radiol 17:873–887PubMedCrossRefGoogle Scholar
  21. 21.
    Warner E, Messersmith H, Causer P, Eisen A, Shumal R, Plewes D (2008) Systematic review: using magnetic resonance imaging to screen women at high risk for breast cancer. Ann Intern Med 148:671–679PubMedGoogle Scholar
  22. 22.
    Breast Imaging Reporting and Data System (BI-RADS) (2003) Ultrasound, mammography and magnetic resonance atlas. American College of Radiology, Reston, VAGoogle Scholar
  23. 23.
    Kuhl CK, Schrading S, Bieling HB, Wardelmann E, Leutner CC, Koenig R, Kuhn W, Schild HH (2007) MRI for diagnosis of pure ductal carcinoma in situ: a prospective observational study. Lancet 370:485–492PubMedCrossRefGoogle Scholar
  24. 24.
    Schouten van der Velden AP, Schlooz-Vries MS, Boetes C, Wobbes T (2009) Magnetic resonance imaging of ductal carcinoma in situ: what is its clinical application? A review. Am J Surg 198(2):262–269PubMedCrossRefGoogle Scholar
  25. 25.
    Berg WA, Guttierrez L, NessAiver MS, Carter WB, Bhargavan M, Lewis RS, Ioffe OB (2004) Diagnostic accuracy of mammography, clinical examination, US, and MR Imaging in preoperative assessment of breast cancer. Radiology 233:830–849PubMedCrossRefGoogle Scholar
  26. 26.
    Menell JH, Morris EA, Dershaw DD, Abramson AF, Brogi E, Liberman L (2005) Determination of the presence and extent of pure ductal carcinoma in situ by mammography and magnetic resonance imaging. Breast J 6:382–390CrossRefGoogle Scholar
  27. 27.
    Facius M, Renz DM, Neubauer H, Böttcher J, Gajda M, Camara O, Kaiser WA (2007) Characteristics of ductal carcinoma in situ in magnetic resonance imaging. Clin Imaging 3:394–400CrossRefGoogle Scholar
  28. 28.
    Rosen EL, Smith-Foley SA, DeMartini WB, Eby PR, Peacock S, Lehman CD (2008) BI-RADS MRI enhancement characteristics of ductal carcinoma in situ. Breast J 13(6):545–550CrossRefGoogle Scholar
  29. 29.
    Vogl G, Dietze O, Hauser-Kronberger C (2005) Angiogenic potential of ductal carcinoma in situ (DCIS) of human breast. Histopathology 47:617–624PubMedCrossRefGoogle Scholar
  30. 30.
    Guidi AJ, Schnitt SJ, Fischer L, Tognazzi K, Harris JR, Dvorak HF, Brown LF (1997) Vascular permeability factor (Vascular endothelial growth factor) expression and angiogenesis in patients with ductal carcinoma in situ of the breast. Cancer 80(10):1945–1953PubMedCrossRefGoogle Scholar
  31. 31.
    Santamaria G, Velasco M, Farrus B, Zanon G, Fernandez PL (2008) Pre-operative MRI of pure intraductal breast carcinoma: a valuable adjunct to mammography in assessing cancer extent. Breast 17:186–194PubMedCrossRefGoogle Scholar
  32. 32.
    Rausch DR, Hendrick RE (2006) How to optimize clinical breast MR Imaging practices and techniques on your 1.5-Tesla system. RadioGraphics 26:1469–1484PubMedCrossRefGoogle Scholar
  33. 33.
    Kuhl C (2007) The current status of breast MR Imaging. Radiology 244(2):356–378PubMedCrossRefGoogle Scholar
  34. 34.
    Tilanus-Linthorst MM, Obdeijn IM, Hop WC, Causer PA, Leach MO, Warner E, Pointon L, Hill K, Klijn JG, Warren RM, Gilbert FJ (2007) BRCA1 mutation and young age predict fast breast cancer growth in the Dutch, United Kingdom, and Canadian magnetic resonance imaging screening trials. Clin Cancer Res 13(24):7357–7362PubMedCrossRefGoogle Scholar
  35. 35.
    Warren RM, Pointon L, Thompson D, Hoff R, Gilbert FJ, Padhani A, Easton D, Lakhani SR, Leach MO, UK Magnetic Resonance Imaging in breast screening (MARIBS) Group (2005) Reading protocol for dynamic contrast-enhanced MR images of the breast: sensitivity and specificity analysis. Radiology 236(3):779–788PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Inge-Marie A. Obdeijn
    • 1
  • Claudette E. Loo
    • 2
  • Adriana J. Rijnsburger
    • 3
  • Martin N. J. M. Wasser
    • 4
  • Elisabeth Bergers
    • 5
  • Theo Kok
    • 6
  • Jan G. M. Klijn
    • 3
  • Carla Boetes
    • 7
    • 8
  1. 1.Department of RadiologyErasmus MC-Daniel den Hoed Cancer CenterRotterdamThe Netherlands
  2. 2.Department of Radiology, Netherlands Cancer InstituteAntoni van Leeuwenhoek HospitalAmsterdamThe Netherlands
  3. 3.Department of Medical Oncology, Family Cancer ClinicErasmus MC-Daniel den Hoed Cancer CenterRotterdamThe Netherlands
  4. 4.Department of RadiologyLeiden University Medical CenterLeidenThe Netherlands
  5. 5.Department of RadiologyVU University Medical CenterAmsterdamThe Netherlands
  6. 6.Department of RadiologyGroningen University Medical CenterGroningenThe Netherlands
  7. 7.Department of RadiologyRadboud University Medical CenterNijmegenThe Netherlands
  8. 8.Department of RadiologyMaastricht University Medical CenterMaastrichtThe Netherlands

Personalised recommendations