Skip to main content

Advertisement

SpringerLink
Log in

The Impact of Breast Density on Breast Cancer Risk and Breast Screening

  • Local-Regional Evaluation and Therapy (KK Hunt, Section Editor)
  • Published:
Current Breast Cancer Reports Aims and scope Submit manuscript

Abstract

Whether measured by qualitative assessment of the parenchyma pattern or quantitatively by percent mammographic density, breast density is consistently a strong and independent risk factor for breast cancer (BC). Density is also a relatively common risk factor, and therefore an important contributor to BC risk at a population level. Including density (with other risk factors) in risk prediction models improves predictive accuracy; however, better standardization and/or automation of density measures will make the integration of breast density into risk assessment, and its application in tailored screening and primary prevention, more feasible. High breast density reduces screening sensitivity and is associated with risk of interval BC in screening; it is also associated with cancers that have poorer prognostic features. Non-randomized studies of adjunct ultrasound screening in women with mammography-negative dense breasts have provided evidence on incremental detection of BC with adjunct ultrasound and high false-positives but have not examined impact on clinical end-points, mortality, or balance of potential benefits versus harms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

Papers of particular interest published recently, have been highlighted as: • Of importance

  1. Byrne C, Schairer C, Wolfe J, et al. Mammographic features and breast cancer risk: effects with time, age, and menopause status. J Natl Cancer Inst. 1995;87:1622–9.

    Article  PubMed  CAS  Google Scholar 

  2. McCormack V, Dos Santos S. Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomark Prev. 2006;15(6):1159–69.

    Article  Google Scholar 

  3. Vacek PM, Geller BM. Prospective study of breast cancer risk using routine mammographic breast density measurements. Cancer Epidemiol Biomark Prev. 2004;13(5):715–22.

    Google Scholar 

  4. Barlow WE, White E, Ballard-Barbash R, et al. Prospective breast cancer risk prediction model for women undergoing screening mammography. J Natl Cancer Inst. 2006;98:1204–14.

    Article  PubMed  Google Scholar 

  5. Ziv E, Shepherd J, Smith-Bindman R, Kerlikowske K. Mammographic breast density and family history of breast cancer. J Natl Cancer Inst. 2003;95:556–8.

    Article  PubMed  Google Scholar 

  6. Vachon C, Kuni C, Anderson K, Anderson V, Sellers T. Association of mammographically defined percent breast density with epidemiologic risk factors for breast cancer. Cancer Causes Control. 2000;11:653–62.

    Article  PubMed  CAS  Google Scholar 

  7. Carney P, Miglioretti D, Yankaskas B, et al. Individual and combined effects of age, breast density and hormone replacement therapy use on the accuracy of screening mammography. Ann Intern Med. 2003;138:168–75.

    PubMed  Google Scholar 

  8. Cummings SR, Tice JA, Bauer S, et al. Prevention of breast cancer in postmenopausal women: approaches to estimating and reducing risk. J Natl Cancer Inst. 2009;101:384–98.

    Article  PubMed  Google Scholar 

  9. Boyd NF, Lockwood GA, Byng JW, Tritchler DL, Yaffe MJ. Mammographic densities and breast cancer risk. Cancer Epidemiol Biomark Prev. 1998;7:1133–44.

    CAS  Google Scholar 

  10. Warner E, Lockwood GA, Tritchler DL, Boyd NF. The risk of breast cancer associated with mammographic parenchymal patterns: a meta-analysis of the published literature to examine the effect of method of classification. Cancer Detect Prev. 1992;16:67–72.

    PubMed  CAS  Google Scholar 

  11. Kerlikowske K. The mammogram that cried Wolfe. N Engl J Med. 2007;356:297–300.

    Article  PubMed  CAS  Google Scholar 

  12. Kerlikowske K, Grady D, Barclay J, Sickles EA, Ernster V. Effect of age, breast density, and family history on the sensitivity of first screening mammography. JAMA. 1996;276:33–8.

    Article  PubMed  CAS  Google Scholar 

  13. Greendale GA, Reboussin BA, Sie A, et al. Effects of estrogen and estrogen-progestin on mammographic parenchymal density. Ann Intern Med. 1999;130:262–9.

    PubMed  CAS  Google Scholar 

  14. Boyd N, Martin L, Stone J, Little L, Minkin S, Yaffe M. A longitudinal study of the effects of menopause on mammographic features. Cancer Epidemiol Biomark Prev. 2002;11:1048–53.

    Google Scholar 

  15. White E, Velentgas P, Mandelson MT, et al. Variation in mammographic breast density by timein menstrual cycle among women aged 40 to 49 years. J Natl Cancer Inst. 1998;90:906–10.

    Article  PubMed  CAS  Google Scholar 

  16. Warwick J, Pinney E, Warren R, et al. Breast density and breast cancer risk factors in a high-risk population. Breast. 2003;12:10–6.

    Article  PubMed  CAS  Google Scholar 

  17. El-Bastawissi AY, White E, Mandelson MT, Taplin SH. Reproductive and hormonal factors associated with mamographic breast density by age. Cancer Causes Control. 2000;11:955–63.

    Article  PubMed  CAS  Google Scholar 

  18. Rutter CM, Mandelson MT, Laya MB, Seger DJ, Taplin S. Changes in breast density associated with initiation, discontinuation, and continuing use of hormone replacement therapy. JAMA. 2001;285:171–6.

    Article  PubMed  CAS  Google Scholar 

  19. Greendale G, Reboussin B, Slone S, et al. Postmenopausal hormone therapy and change in mammographic density. J Natl Cancer Inst. 2003;95:30–7.

    Article  PubMed  CAS  Google Scholar 

  20. Reinier K, Vacek P, Geller B. Risk factors for breast carcinoma in situ versus invasive breast cancer in a prospective study of pre- and post-menopausal women. Breast Cancer Res Treat. 2006;103:343–8.

    Article  PubMed  Google Scholar 

  21. MacKenzie T, Titus-Ernstoff L, Vacek P, et al. Breast density in relation to risk of ductal carcinoma in situ of the breast in women undergoing screening mammography. Cancer Causes Control. 2007;18:939–45.

    Article  PubMed  Google Scholar 

  22. Gill J, Maskarinec G, Pagano I, Kolonel L. The association of mammographic density with ductal carcinoma in situ of the breast: the Multiethnic Cohort. Breast Cancer Res. 2006;8:R30.

    Article  PubMed  Google Scholar 

  23. Ziv E, Tice J, Smith-Bindman R, Shepherd J, Cummings S, Kerlikowske K. Mammographic density and estrogen receptor status of breast cancer. Cancer Epidemiol Biomark Prev. 2004;13(12):2090–5.

    CAS  Google Scholar 

  24. Ma H, Luo J, Press M, Wang Y, Bernstein L, Ursin G. Is there a difference in the association between percent mammographic density and subtypes of breast cancer? Luminal A and triple-negative breast cancer. Cancer Epidemiol Biomark Prev. 2009;18(2):479–85.

    Article  CAS  Google Scholar 

  25. Aiello E, Buist D, White E, Porter P. Association between mammographic breast density and breast cancer tumor characteristics. Cancer Epidemiol Biomark Prev. 2005;14:662–8.

    Article  Google Scholar 

  26. Fasching PA, Heusinger K, Loehberg CR. Influence of mammographic breast density on the diagnotic accuracy of tumor size asessment and association iwth breast cancer tumor characteristics. Eur J Radiol. 2006;60:398–404.

    Article  PubMed  Google Scholar 

  27. Yang WT, Dryden M, Broglio K. Mammographic features of triple receptor-negative primary breast cancers in young premenopausal women. Breast Cancer Res Treat. 2008;111:405–10.

    Article  PubMed  Google Scholar 

  28. Chen JH, Hsu F, Shih H. Does breast density show difference in patients with estrogen receptor-positive and estrogen receptor-negative breast cancer measured on MRI? Ann Oncol. 2009;20:1447–9.

    Article  PubMed  Google Scholar 

  29. Conroy S, Pagano I, Kolonel L, Maskarinec G. Mammographic density and hormone receptor expression in breast cancer: The Multiethnic Cohort Study. Cancer Epidemiol. 2011;Jan 17. [Epub ahead of print].

  30. Ding J, Warren R, Girling A, Thompson D, Easton D. Mammographic density, estrogen receptor status and other breast cancer tumor characteristics. Breast J. 2010;16:279–89.

    Article  PubMed  Google Scholar 

  31. • Yaghjyan L, Colditz GA, Collins L, et al. Mammographic breast density and subsequent risk of breast cancer in postmenopausal women according to tumor characteristics. J Natl Cancer Inst. 2011;103(15):1179–89. This study highlights that breast density is associated with all subtypes of breast cancer.

    Article  PubMed  Google Scholar 

  32. Ma H, Wang Y, Sullivan-Halley J, et al. Breast cancer receptor status: do results from a centralized pathology laboratory agree with SEER registry reports? Cancer Epidemiol Biomark Prev. 2009;18:2214–20.

    Article  CAS  Google Scholar 

  33. Ghosh K, Brandt K, Sellers T, et al. Association of mammographic density with the pathology of subsequent breast cancer among postmenopausal women. Cancer Epidemiol Biomark Prev. 2008;17:872–9.

    Article  Google Scholar 

  34. Porter G, Evans A, Cornford E, et al. Influence of mammographic parenchymal pattern in screening-detected and interval invasive breast cancers on pathologic features, mammographic features, and patient survival. AJR Am J Roentgenol. 2007;188:676–83.

    Article  PubMed  Google Scholar 

  35. Sala E, Solomon L, Warren R, et al. Size, node status and grade of breast tumours: association with mammographic parenchymal patterns. Eur Radiol. 2000;10:157–61.

    Article  PubMed  CAS  Google Scholar 

  36. Roubidoux M, Bailey J, Wray L, Helvie M. Invasive cancers detected after breast cancer screening yielded a negative result: relationship of mammographic density to tumor prognostic factors. Radiology. 2004;230:42–8.

    Article  PubMed  Google Scholar 

  37. • Kerlikowske K, Cook A, Buist DSM, et al. Breast cancer risk by breast density, age, menopause, and postmenopausal hormone therapy use. J Clin Oncol. 2010;28(24):3830–7. This work highlights the interaction between breast density, postmenopausal hormone therapy use, and the risk of breast cancer. It indicates that tumors in dense breasts may progress more rapidly than those in fatty breast.

    Article  PubMed  Google Scholar 

  38. Cil T, Fishell E, Hanna W, et al. Mammographic density and the risk of breast cancer recurrence after breast-conserving surgery. Cancer. 2009;115(24):5780–7.

    Article  PubMed  Google Scholar 

  39. Habel L, Capra A, Achacoso N, et al. Mammographic density and risk of second breast cancer after ductal carcinoma in situ. Cancer Epidemiol Biomark Prev. 2010;19:2488–95.

    Article  Google Scholar 

  40. Habel LA, Dignam J, Land S, Salane M, Capra AM, Julian T. Mammographic density and breast cancer after ductal carcinoma in situ. J Natl Cancer Inst. 2004;96:1467–72.

    Article  PubMed  Google Scholar 

  41. Hwang ES, Miglioretti DL, Ballard-Barbash R, Weaver DL, Kerlikowske K. Association between breast density and subsequent breast cancer following treatment for ductal carcinoma in situ. Cancer Epidemiol Biomark Prev. 2007;16(12):2587–93.

    Article  Google Scholar 

  42. Park C, Rembert J, Moore D, Kerlikowske K. High mammographic breast density and obesity are associated with increased local recurrence following lumpectomy and radiation therapy for invasive breast cancer. Int J Radiat Oncol Biol Phys. 2009;73(1):75–9.

    Article  PubMed  Google Scholar 

  43. • Tice JA, Cummings SR, Smith-Bindman R, Ichikawa L, Barlow WE, Kerlikowske K. Using clinical factors and mammographic breast density to estimate breast cancer risk: development and validation of a new predictive model. Ann Intern Med. 2008;148(5):337–47. A risk prediction model (BCSC Breast Density 5-year risk model) that incorporates BI-RADS density with conventional risk factors (age, race, family history of breast cancer, history of breast biopsy) shows improved predictive accuracy with integration of density.

    PubMed  Google Scholar 

  44. Chen J, Pee D, Ayyagari R, et al. Projecting absolute invasive breast cancer risk in white women with a model that includes mammographic density. J Natl Cancer Inst. 2006;98(17):1215–26.

    Article  PubMed  Google Scholar 

  45. Ciatto S, Houssami N, Apruzzese A, et al. Categorizing breast mammographic density: intra- and interobserver reproducibility of BI-RADS density categories. Breast. 2005;14:269–75.

    Article  PubMed  CAS  Google Scholar 

  46. Kerlikowske K, Grady D, Barclay J, et al. Variability and accuracy in mammographic interpretation using the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS). J Natl Cancer Inst. 1998;90:1801–9.

    Article  PubMed  CAS  Google Scholar 

  47. • Shepherd J, Kerlikowske K, Ma L, et al. Volume of dense breast tissue and risk of breast cancer. Cancer Epidemiol Biomark Prev. 2011;20:1473–82 This study demonstrates the association between volumetric breast density and risk of breast cancer.

    Article  Google Scholar 

  48. Marias K, Behrenbruch C, Highnam R, Parbhoo S, Seifalian A, Brady M. A mammographic image analysis method to detect and measure changes in breast density. Eur J Radiol. 2004;52:276–82.

    Article  PubMed  Google Scholar 

  49. Kaufhold J, Thomas J, Eberhard J, Galbo C, Trotter D. A calibration approach to glandular tissue composition estimation in digital mammography. Med Phys. 2002;29:1867–80.

    Article  PubMed  CAS  Google Scholar 

  50. Heine J, Fowler E, Flowers C. Full field digital mammography and breast density: comparison of calibrated and noncalibrated measurements. Acad Radiol. 2011;18:1430–6.

    Article  PubMed  Google Scholar 

  51. Houssami N, Irwig L, Ciatto S. Radiological surveillance of interval breast cancers in screening programmes. Lancet Oncol. 2006;7(3):259–65.

    Article  PubMed  Google Scholar 

  52. Mandelson MT, Oestreicher N, Porter PL, et al. Breast density as a predictor of mammographic detection: comparison of interval- and screen-detected cancers. J Natl Cancer Inst. 2000;92(13):1081–7.

    Article  PubMed  CAS  Google Scholar 

  53. Chiarelli AM, Kirsh VA, Klar NS, et al. Influence of patterns of hormone replacement therapy use and mammographic density on breast cancer detection. Cancer Epidemiol Biomark Prev. 2006;15(10):1856–62.

    Article  CAS  Google Scholar 

  54. Boyd NF, Guo H, Martin LJ, et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med. 2007;356(3):227–36.

    Article  PubMed  CAS  Google Scholar 

  55. Ciatto S, Visioli C, Paci E, Zappa M. Breast density as a determinant of interval cancer at mammographic screening. Br J Cancer. 2004;90(2):393–6.

    Article  PubMed  CAS  Google Scholar 

  56. • Houssami N, Abraham LA, Miglioretti DL, et al. Accuracy and outcomes of screening mammography in women with a personal history of early-stage breast cancer. JAMA. 2011;305(8):790–9. This study shows a signifcant association between density and breast screening outcomes in a very large cohort of women with a previous breast cancer.

    Article  PubMed  CAS  Google Scholar 

  57. Olsen AH, Bihrmann K, Jensen MB, Vejborg I, Lynge E. Breast density and outcome of mammography screening: a cohort study. Br J Cancer. 2009;100(7):1205–8.

    Article  PubMed  CAS  Google Scholar 

  58. • Kavanagh AM, Byrnes GB, Nickson C, et al. Using mammographic density to improve breast cancer screening outcomes. Cancer Epidemiol Biomark Prev. 2008;17(10):2818–24. This study demonstrates the association of breast density with risk of interval breast cancers in screening, and the association of increasing breast density with risk of cancers that have poorer prognosis.

    Article  Google Scholar 

  59. Chiu SYH, Duffy S, Yen AMF, Tabar L, Smith RA, Chen HH. Effect of baseline breast density on breast cancer incidence, stage, mortality, and screening parameters: 25-year follow-up of a Swedish mammographic screening. Cancer Epidemiol Biomark Prev. 2010;19(5):1219–28.

    Article  Google Scholar 

  60. • Schousboe J, Kerlikowske K, Loh A, Cummings S. Personalizing mammography by breast density and other risk factors for breast cancer: analysis of health benefits and cost-effectiveness. Ann Intern Med. 2011;155:10–20. This article presents a decision-analytic evaluation of the benefits and harms of risk-based (defining risk with age, breast density, and family history) screening for breast cancer.

    PubMed  Google Scholar 

  61. Cuzick J, Warwick J, Pinney E, Warren R, Duffy S. Tamoxifen and breast density in women at increased risk of breast cancer. J Natl Cancer Inst. 2004;96(8):621–8.

    Article  PubMed  CAS  Google Scholar 

  62. Cuzick J, Powles T, Veronesi U, et al. Overview of the main outcomes in breast-cancer prevention trials. Lancet. 2003;361(9354):296–300.

    Article  PubMed  CAS  Google Scholar 

  63. • Cuzick J, Warwick J, Pinney E, et al. Tamoxifen-Induced reduction in mammographic density and breast cancer risk reduction: A Nested Case–Control Study. J Natl Cancer Inst. 2011;103:744–52. This study shows that breast density’s response to tamoxifen is associated with cancer outcome.

    Article  PubMed  CAS  Google Scholar 

  64. Kerlikowske K, Ichikawa L, Miglioretti D, et al. Longitudinal measurement of clinical mammographic breast density improves estimation of breast cancer risk. J Natl Cancer Inst. 2007;99:386–95.

    Article  PubMed  Google Scholar 

  65. Glasziou P, Houssami N. The evidence base for breast cancer screening. Prev Med. 2011;53(3).

  66. Pisano ED, Gatsonis C, Hendrick E, et al. Diagnostic performance of digital versus film mammography for breast-cancer screening. N Engl J Med. 2005;353(17):1773–83.

    Article  PubMed  CAS  Google Scholar 

  67. Houssami N, Lord SJ, Ciatto S. Breast cancer screening: emerging role of new imaging techniques as adjuncts to mammography. Med J Aust. 2009;190(9):493–8.

    PubMed  Google Scholar 

  68. Houssami N, Ciatto S. The evolving role of new imaging methods in breast screening. Prev Med. 2011;53(3):123–6.

    Article  PubMed  Google Scholar 

  69. Buchberger W, Niehoff A, Obrist P, DeKoekkoek-Doll P, Dunser M. Clinically and mammographically occult breast lesions: detection and classification with high-resolution sonography. Semin Ultrasound CT MRI. 2000;21(4):325–36.

    Article  CAS  Google Scholar 

  70. Kaplan SS. Clinical utility of bilateral whole-breast US in the evaluation of women with dense breast tissue. Radiology. 2001;221(3):641–9.

    Article  PubMed  CAS  Google Scholar 

  71. Kolb TM, Lichy J, Newhouse JH. 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. 2002;225(1):165–75.

    Article  PubMed  Google Scholar 

  72. Corsetti V, Houssami N, Ferrari A, et al. Breast screening with ultrasound in women with mammography-negative dense breasts: evidence on incremental cancer detection and false positives, and associated cost. Eur J Cancer. 2008;44(4):539–44.

    Article  PubMed  Google Scholar 

  73. Berg WA, Blume JD, Cormack JB, et al. Combined screening with ultrasound and mammography vs mammography alone in women at elevated risk of breast cancer. JAMA. 2008;299(18):2151–63.

    Article  PubMed  CAS  Google Scholar 

  74. • Corsetti V, Houssami N, Ghirardi M, et al. Evidence of the effect of adjunct ultrasound screening in women with mammography-negative dense breasts: Interval breast cancers at one year follow-up. Eur J Cancer. 2011;47:1021–6. This article presents data on interval breast cancers in women with mammography-negative dense breasts who received ultrasound, suggesting a potential benefit.

    Article  PubMed  Google Scholar 

  75. Gram IT, Funkhouser E, Tabar L. The Tabar classification of mammographic parenchymal patterns. Eur J Radiol. 1997;24(2):131–6.

    Article  PubMed  CAS  Google Scholar 

Download references

Disclosure

No conflicts of interest relevant to this article were reported.

Author information

Authors and Affiliations

  1. Screening and Test Evaluation Program, School of Public Health (A27), Sydney Medical School, University of Sydney, Sydney, 2006, Australia

    Nehmat Houssami

  2. Departments of Medicine and Epidemiology and Biostatistics, University of California, San Francisco, CA, USA

    Karla Kerlikowske

Authors
  1. Nehmat Houssami
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karla Kerlikowske
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nehmat Houssami.

Additional information

This work was partly funded by National Health and Medical Research Council (NHMRC) program grant 633003 to the Screening & Test Evaluation Program.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Houssami, N., Kerlikowske, K. The Impact of Breast Density on Breast Cancer Risk and Breast Screening. Curr Breast Cancer Rep 4, 161–168 (2012). https://doi.org/10.1007/s12609-012-0070-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12609-012-0070-z

Keywords

Search

Navigation