Breast Cancer Research and Treatment

, Volume 100, Issue 1, pp 109–119 | Cite as

Factors Affecting Sensitivity and Specificity of Screening Mammography and MRI in Women with an Inherited Risk for Breast Cancer

  • Mieke Kriege
  • Cecile T. M. Brekelmans
  • Inge Marie Obdeijn
  • Carla Boetes
  • Harmine M. Zonderland
  • Sara H. Muller
  • Theo Kok
  • Radu A. Manoliu
  • A. Peter E. Besnard
  • Madeleine M. A. Tilanus-Linthorst
  • Caroline Seynaeve
  • Carina C. M. Bartels
  • Reini Kaas
  • Siebren Meijer
  • Jan C. Oosterwijk
  • Nicoline Hoogerbrugge
  • Rob A. E. M. Tollenaar
  • Emiel J. T. Rutgers
  • Harry J. de Koning
  • Jan G. M. Klijn
Epidemiology

Abstract

Background

The MRISC study is a screening study, in which women with an increased risk of hereditary breast cancer are screened by a yearly mammography and MRI, and half-yearly clinical breast examination. The sensitivity found in this study was 40% for mammography and 71% for MRI and the specificity was 95 and 90%, respectively. In the current subsequent study we investigated whether these results are influenced by age, a BRCA1/2 mutation, menopausal status and breast density.

Patients and methods

From November 1999 to October 2003, 1909 eligible women were screened and 50 breast cancers were detected. For the current analysis, data of 4134 screening rounds and 45 detected breast cancers were used. For both imaging modalities, screening parameters, receiver operating characteristic (ROC) curves and uni- and multivariate odds ratios (ORs) were calculated. All analyses were separately performed for age at entry (< 40, 40–49, ≥50), mutation status, menopausal status and breast density.

Results

Sensitivity of MRI was decreased in women with high breast density (adjusted OR 0.08). False-positive rates of both mammography (ORadj 1.67) and MRI (ORadj 1.21) were increased by high breast density, that of MRI by pre-menopausal status (ORadj 1.70), young age (ORadj 1.58 for women 40–49 years versus women ≥50 years) and decreased in BRCA1/2 mutation carriers (ORadj 0.74).

In all investigated subgroups the discriminating capacity (measured by the area under the ROC-curve) was higher for MRI than for mammography, with the largest differences for BRCA1/2 mutation carriers (0.237), for women between 40 and 49 years (0.227) and for women with a low breast density (0.237).

Conclusions

This report supports the earlier recommendation that MRI should be a standard screening method for breast cancer in BRCA1/2 mutation carriers.

Key words

Age BRCA1 BRCA2 Breast cancer screening Breast density Mammography Menopausal status MRI Sensitivity Specificity 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Notes

Acknowledgement

Supported by a grant (OG 98-03) from the Dutch Health Insurance Council.

References

  1. 1.
    Vasen HFA, Haites NE, Evans DGR et al (1998) Current policies for surveillance and management in women at risk of breast and ovarian cancer: a survey among 16 european family cancer clinics. Eur J Cancer 34:1922–1926PubMedCrossRefGoogle Scholar
  2. 2.
    Brekelmans CT, Seynaeve C, Bartels CC et al (2001) Effectiveness of breast cancer surveillance in BRCA1/2 gene mutation carriers and women with high familial risk. J Clin Oncol 19:924–930PubMedGoogle Scholar
  3. 3.
    Scheuer L, Kauff N, Robson M et al (2002) Outcome of preventive surgery and screening for breast and ovarian cancer in BRCA mutation carriers. J Clin Oncol 20:1260–1268PubMedCrossRefGoogle Scholar
  4. 4.
    Komenaka IK, Ditkoff BA, Joseph KA et al (2004) The development of interval breast malignancies in patients with BRCA mutations. Cancer 100:2079–2083PubMedCrossRefGoogle Scholar
  5. 5.
    Kriege M, Brekelmans CT, Boetes C et al (2001) MRI screening for breast cancer in women with familial or genetic predisposition: design of the Dutch national study (MRISC). Fam Cancer 1:163–168PubMedCrossRefGoogle Scholar
  6. 6.
    Kriege M, Brekelmans CT, Boetes C et al (2004) Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition. N Engl J Med 351:427–437PubMedCrossRefGoogle Scholar
  7. 7.
    Warner E, Plewes DB, Hill KA et al (2004) Surveillance of BRCA1 and BRCA2 mutation carriers with magnetic resonance imaging, ultrasound, mammography, and clinical breast examination. JAMA 292:1317–1325PubMedCrossRefGoogle Scholar
  8. 8.
    Leach MO, Boggis CR, Dixon AK et al (2005) 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 365:1769–1778PubMedCrossRefGoogle Scholar
  9. 9.
    Kuhl CK, Schrading S, Leutner CC et al (2005) Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer. J Clin Oncol 23:8469–8476PubMedCrossRefGoogle Scholar
  10. 10.
    Litherland JC, Stallard S, Hole D et al (1999) The effect of hormone replacement therapy on the sensitivity of screening mammograms. Clin Radiol 54:285–288PubMedCrossRefGoogle Scholar
  11. 11.
    Kerlikowske K, Grady D, Barclay J et al (1996) Effect of age, breast density, and family history on the sensitivity of first screening mammography. JAMA 276:33–38PubMedCrossRefGoogle Scholar
  12. 12.
    Rosenberg RD, Hunt WC, Williamson MR et al (1998) 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 209:511–518PubMedGoogle Scholar
  13. 13.
    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 evaluations. Radiology 225:165–175PubMedGoogle Scholar
  14. 14.
    Tabar L, Fagerberg G, Chen HH et al (1995) Efficacy of breast cancer screening by age. New results from the Swedish two-county trial. Cancer 75:2507–2517PubMedCrossRefGoogle Scholar
  15. 15.
    Fletcher SW, Black W, Harris R et al (1993) Report of the international workshop on screening for breast cancer. J Natl Cancer Inst 85:1644–1656PubMedGoogle Scholar
  16. 16.
    Carney PA, Miglioretti DL, Yankaskas BC et al (2003) Individual and combined effects of age, breast density, and hormone replacement therapy use on the accuracy of screening mammography. Ann Intern Med 138:168–175PubMedGoogle Scholar
  17. 17.
    Ciatto S, Visioli C, Paci E et al (2004) Breast density as a determinant of interval cancer at mammographic screening. Br J Cancer 90:393–396PubMedCrossRefGoogle Scholar
  18. 18.
    Saarenmaa I, Salminen T, Geiger U et al (2001) The effect of age and density of the breast on the sensitivity of breast cancer diagnostic by mammography and ultasonography. Breast Cancer Res Treat 67:117–123PubMedCrossRefGoogle Scholar
  19. 19.
    Banks E, Reeves G, Beral V et al (2004) Influence of personal characteristics of individual women on sensitivity and specificity of mammography in the Million Women Study: cohort study. Br Med J 329:477Google Scholar
  20. 20.
    Tilanus-Linthorst M, Verhoog L, Obdeijn IM et al (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
  21. 21.
    Halapy E, Chiarelli AM, Klar N et al (2005) Accuracy of breast screening among women with and without a family history of breast and/or ovarian cancer. Breast Cancer Res Treat 90:299–305PubMedCrossRefGoogle Scholar
  22. 22.
    van Gils CH, Otten JD, Verbeek AL et al (1998) Effect of mammographic breast density on breast cancer screening performance: a study in Nijmegen, the Netherlands. J Epidemiol Commun Health 52:267–271CrossRefGoogle Scholar
  23. 23.
    Mandelson MT, Oestreicher N, Porter PL et al (2000) Breast density as a predictor of mammographic detection: comparison of interval- and screen-detected cancers. J Natl Cancer Inst 92:1081–1087PubMedCrossRefGoogle Scholar
  24. 24.
    Kavanagh AM, Mitchell H, Giles GG (2000) Hormone replacement therapy and accuracy of mammographic screening. Lancet 355:270–274PubMedCrossRefGoogle Scholar
  25. 25.
    Blanks RG, Moss SM, McGahan CE et al (2000) Effect of NHS breast screening programme on mortality from breast cancer in England and Wales, 1990–8: comparison of observed with predicted mortality. Br Med J 321:665–669CrossRefGoogle Scholar
  26. 26.
    Kavanagh AM, Cawson J, Byrnes GB et al (2005) Hormone replacement therapy, percent mammographic density, and sensitivity of mammography. Cancer Epidemiol Biomarkers Prev 14:1060–1064PubMedCrossRefGoogle Scholar
  27. 27.
    Thurfjell EL, Holmberg LH, Persson IR (1997) Screening mammography: sensitivity and specificity in relation to hormone replacement therapy. Radiology 203:339–341PubMedGoogle Scholar
  28. 28.
    Sardanelli F, Giuseppetti GM, Panizza P et al (2004) Sensitivity of MRI versus mammography for detecting foci of multifocal, multicentric breast cancer in Fatty and dense breasts using the whole-breast pathologic examination as a gold standard. AJR Am J Roentgenol 183:1149–1157PubMedGoogle Scholar
  29. 29.
    Bluemke DA, Gatsonis CA, Chen MH et al (2004) Magnetic resonance imaging of the breast prior to biopsy. JAMA 292:2735–2742PubMedCrossRefGoogle Scholar
  30. 30.
    Berg WA, Gutierrez L, NessAiver MS et al (2004) Diagnostic accuracy of mammography, clinical examination, US, and MR imaging in preoperative assessment of breast cancer. Radiology 233:830–849PubMedGoogle Scholar
  31. 31.
    Harms SE (1998) Breast magnetic resonance imaging. Semin Ultrasound CT MR 19:104–120PubMedCrossRefGoogle Scholar
  32. 32.
    Heywang-Kobrunner SH, Viehweg P, Heinig A et al (1997) Contrast-enhanced MRI of the breast: accuracy, value, controversies, solutions. Eur J Radiol 24:94–108PubMedCrossRefGoogle Scholar
  33. 33.
    Kinkel K, Hylton NM (2001) Challenges to interpretation of breast MRI. J Magn Reson Imaging 13:821–829PubMedCrossRefGoogle Scholar
  34. 34.
    Kuhl CK, Bieling HB, Gieseke J et al (1997) Healthy premenopausal breast parenchyma in dynamic contrast-enhanced MR imaging of the breast: normal contrast medium enhancement and cyclical-phase dependency. Radiology 203:137–144PubMedGoogle Scholar
  35. 35.
    Muller-Schimpfle M, Ohmenhauser K, Stoll P et al (1997) Menstrual cycle and age: influence on parenchymal contrast medium enhancement in MR imaging of the breast. Radiology 203:145–149PubMedGoogle Scholar
  36. 36.
    Claus EB, Risch NJ, Thompson WD (1994) Autosomal dominant inheritance of early-onset breast cancer. Cancer 73:643–651PubMedCrossRefGoogle Scholar
  37. 37.
    American College of Radiology (1995) Illustrated breast imaging reporting and data system (BI-RADS). 3Google Scholar
  38. 38.
    Berg WA, Campassi C, Langenberg P et al (2000) Breast imaging reporting and data system: inter- and intraobserver variability in feature analysis and final assessment. AJR Am J Roentgenol 174:1769–1777PubMedGoogle Scholar
  39. 39.
    Lee-Han H, Cooke G, Boyd NF (1995) Quantitative evaluation of mammographic densities: a comparison of methods of assessment. Eur J Cancer Prev 4:285–292PubMedGoogle Scholar
  40. 40.
    Sivaramakrishna R, Obuchowski NA, Chilcote WA et al (2001) Automatic segmentation of mammographic density. Acad Radiol 8:250–256PubMedCrossRefGoogle Scholar
  41. 41.
    Ooms EA, Zonderland HM, Eijkemans MJC et al (2006) Mammography: inter-observer variability in breast density assesment (abstract). Fifth international meeting: endocrine treatment prevention of breast ABD gynaecological cancersGoogle Scholar
  42. 42.
    Kaas R, Kroger R, Hendriks JH et al (2004) The significance of circumscribed malignant mammographic masses in the surveillance of BRCA 1/2 gene mutation carriers. Eur Radiol 14: 1647–1653PubMedCrossRefGoogle Scholar
  43. 43.
    Buist DS, Porter PL, Lehman C et al (2004) Factors contributing to mammography failure in women aged 40–49 years. J Natl Cancer Inst 96:1432–1440PubMedCrossRefGoogle Scholar
  44. 44.
    Tilanus-Linthorst MM, Kriege M, Boetes C et al (2005) Hereditary breast cancer growth rates and its impact on screening policy. Eur J Cancer 41:1610–1617PubMedCrossRefGoogle Scholar
  45. 45.
    Day NE, Williams DR, Khaw KT (1989) Breast cancer screening programmes: the development of a monitoring and evaluation system. Br J Cancer 59:954–958PubMedGoogle Scholar
  46. 46.
    Kriege M, Brekelmans CTM, Boetes C et al (2006, in press) Differences between first and subsequent rounds of the MRISC breast cancer screening program for women with a familial or genetic predisposition. CancerGoogle Scholar
  47. 47.
    Adem C, Reynolds C, Soderberg CL et al (2003) Pathologic characteristics of breast parenchyma in patients with hereditary breast carcinoma, including BRCA1 and BRCA2 mutation carriers. Cancer 97:1–11PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B. V. 2006 2006

Authors and Affiliations

  • Mieke Kriege
    • 1
  • Cecile T. M. Brekelmans
    • 1
  • Inge Marie Obdeijn
    • 2
  • Carla Boetes
    • 3
  • Harmine M. Zonderland
    • 4
  • Sara H. Muller
    • 5
  • Theo Kok
    • 6
  • Radu A. Manoliu
    • 7
  • A. Peter E. Besnard
    • 5
  • Madeleine M. A. Tilanus-Linthorst
    • 8
  • Caroline Seynaeve
    • 1
  • Carina C. M. Bartels
    • 8
  • Reini Kaas
    • 9
  • Siebren Meijer
    • 10
  • Jan C. Oosterwijk
    • 11
  • Nicoline Hoogerbrugge
    • 12
  • Rob A. E. M. Tollenaar
    • 13
  • Emiel J. T. Rutgers
    • 9
  • Harry J. de Koning
    • 14
  • Jan G. M. Klijn
    • 1
  1. 1.Family Cancer Clinic, Department of Medical OncologyErasmus MC-Daniel den Hoed Cancer CenterRotterdamthe Netherlands
  2. 2.Family Cancer Clinic, Department of RadiologyErasmus MC-Daniel den Hoed Cancer CenterRotterdamthe Netherlands
  3. 3.Department of RadiologyUniversity Medical CenterNijmegenthe Netherlands
  4. 4.Department of RadiologyLeiden University Medical CenterLeidenthe Netherlands
  5. 5.Department of RadiologyNetherlands Cancer InstituteAmsterdamthe Netherlands
  6. 6.Department of RadiologyUniversity Medical Center, University of GroningenGroningenthe Netherlands
  7. 7.Department of RadiologyVU University Medical CenterAmsterdamthe Netherlands
  8. 8.Family Cancer Clinic, Department of SurgeryErasmus MC-Daniel den Hoed Cancer CenterRotterdamthe Netherlands
  9. 9.Department of SurgeryNetherlands Cancer InstituteAmsterdamthe Netherlands
  10. 10.Department of SurgeryVU University Medical CenterAmsterdamthe Netherlands
  11. 11.Department of Clinical GeneticsUniversity Medical Center, University of GroningenGroningenthe Netherlands
  12. 12.Family Cancer ClinicUniversity Medical CenterNijmegenthe Netherlands
  13. 13.Department of SurgeryLeiden University Medical CenterLeidenthe Netherlands
  14. 14.Department of Public HealthErasmus MCRotterdamthe Netherlands

Personalised recommendations