Mammographic Density as a Potential Surrogate Marker for Breast Cancer



Despite extensive research, the causes of most cases of breast cancer remain unknown, although there is strong evidence that risk of the disease is influenced by both genetic and environmental factors (Veronesi et al. 2005). We consider here the potential role of mammographic density as a surrogate marker in research on the etiology and prevention of breast cancer.


Breast Cancer Breast Cancer Risk Mammographic Density Breast Cancer Risk Factor Percent Density 
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  1. Aiello EJ, Tworoger SS, Yasui Y et al (2005) Associations among circulating sex hormones, insulin-like growth factor, lipids, and mammographic density in postmenopausal women. Cancer Epidemiol Biomarkers Prev 14(6):1411–1417CrossRefPubMedGoogle Scholar
  2. American College of Radiology (ACR) (1998) Breast imaging reporting and data system (BI-RADS). American College of Radiology [Third]. American College of Radiology, RestonGoogle Scholar
  3. Bartow SA, Mettler FA Jr, Black WC III (1997) Correlations between radiographic patterns and morphology of the female breast. Rad Patterns Morph 13:263–275Google Scholar
  4. Beral V, Bull D, Doll R, Peto R, Reeves G (2001) 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 358(9291):1389–1399CrossRefGoogle Scholar
  5. Bérubé S, Diorio C, Verhoek-Oftedahl W, Brisson J, Vitamin D (2004) calcium, and mammographic breast densities. Cancer Epidemiol Biomarkers Prev 13(9):1466–1472PubMedGoogle Scholar
  6. Boyd N, Martin L, Stone J, Little L, Minkin S, Yaffe M (2002) A longitudinal study of the effects of menopause on mammographic features. Cancer Epidemiol Biomarkers Prev 11(10 Pt 1):1048–1053PubMedGoogle Scholar
  7. Boyd NF, Dite GS, Stone J et al (2002) Heritability of mammographic density, a risk factor for breast cancer. N Engl J Med 347(12):886–894CrossRefPubMedGoogle Scholar
  8. Boyd NF, Greenberg C, Lockwood G et al (1997) Effects at two years of a low-fat, high-carbohydrate diet on radiologic features of the breast: results from a randomized trial. Canadian Diet and Breast Cancer Prevention Study Group. J Natl Cancer Inst 89(7):488–496CrossRefPubMedGoogle Scholar
  9. Boyd NF, Guo H, Martin LJ et al (2007) Mammographic density and the risk and detection of breast cancer. N Engl J Med 356(3):227–236CrossRefPubMedGoogle Scholar
  10. Boyd NF, Lockwood GA, Byng J, Tritchler DL, Yaffe M (1998) Mammographic densities and breast cancer risk. Cancer Epidemiol Biomarkers Prev 7(12):1133–1144PubMedGoogle Scholar
  11. Boyd NF, Lockwood GA, Byng JW, Yaffe MJ, Tritchler DL (1998) The relationship of anthropometric measures to radiological features of the breast in premenopausal women. Br J Cancer 78(9):1233–1238PubMedGoogle Scholar
  12. Boyd NF, Martin LJ, Li Q et al (2006) Mammographic density as a surrogate marker for the effects of hormone therapy on risk of breast cancer. Cancer Epidemiol Biomarkers Prev 15(5):961–966CrossRefPubMedGoogle Scholar
  13. Boyd NF, Martin LJ, Sun L et al (2006) Body size, mammographic density and breast cancer risk. Cancer Epidemiol Biomarkers Prev 15(11):2086–2092CrossRefPubMedGoogle Scholar
  14. Boyd NF, Rommens JM, Vogt K et al (2005) Mammographic breast density as an intermediate phenotype for breast cancer. Lancet 6(10):798–808CrossRefGoogle Scholar
  15. Boyd NF, Stone J, Martin LJ et al (2002) The association of breast mitogens with mammographic densities. Br J Cancer 87(8):876–882CrossRefPubMedGoogle Scholar
  16. Bremnes Y, Ursin G, Bjurstam N, Rinaldi S, Kaaks R, Gram IT (2007) Endogenous sex hormones, prolactin and mammographic density in postmenopausal Norwegian women. Int J Cancer 121(11):2506–2511CrossRefPubMedGoogle Scholar
  17. Brisson J, Brisson B, Coté G, Maunsell E, Bérubé S, Robert J (2000) Tamoxifen and mammographic breast densities. Cancer Epidemiol Biomarkers Prev 9(9):911–915PubMedGoogle Scholar
  18. Byrne C, Schairer C, Wolfe J et al (1995) Mammographic features and breast cancer risk: effects with time, age, and menopause status. J Natl Cancer Inst 87(21):1622–1629CrossRefPubMedGoogle Scholar
  19. Carlson CS, Eberle MA, Kruglyak L, Nickerson DA (2004) Mapping complex disease loci in whole-genome association studies. Nature 429(6990):446–452CrossRefPubMedGoogle Scholar
  20. Chlebowski RT, Hendrix SL, Langer R et al (2003) Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women. The Women’s Health Initiative Randomized Trial. JAMA 289(24):3243–3253CrossRefPubMedGoogle Scholar
  21. Cuzick J, Warwick J, Pinney E, Warren RML, Duffy SW (2004) Tamoxifen and breast density in women at increased risk of breast cancer. J Natl Cancer Inst 96(8):621–628CrossRefPubMedGoogle Scholar
  22. Eilertsen AL, Karssemeijer N, Skaane P, Qvigstad E, Sandset PM (2008) Differential impact of conventional and low-dose oral hormone therapy, tibolone and raloxifene on mammographic breast density, assessed by an automated quantitative method. BJOG May;115(6):773–779CrossRefPubMedGoogle Scholar
  23. Fisher B, Costantino JP, Wickerham DL et al (1998) Tamoxifen for prevention of breast cancer: report of the national surgical adjuvant breast and bowel project P-1 study. J Natl Cancer Inst 90(18):1371–1388Google Scholar
  24. Freedman LS, Graubard BI (1992) Statistical validation of intermediate endpoints for chronic diseases. Stat Med 11(2):167–178CrossRefPubMedGoogle Scholar
  25. Freedman M, San Martin J, O’Gorman J et al (2001) Digitized mammography: a clinical trial of postmenopausal women randomly assigned to receive raloxifene, estrogen, or placebo. J Natl Cancer Inst 93(1):51–56CrossRefPubMedGoogle Scholar
  26. Gertig DM, Stillman IE, Byrne C et al (1999) Association of age and reproductive factors with benign breast tissue composition. Cancer Epidemiol Biomarkers Prev 8(10):873–879PubMedGoogle Scholar
  27. Gram IT, Funkhouser E, Tabar L (1997) The Tabar classification of mammographic parenchymal patterns. Eur J Radiol 24(2):131–136CrossRefPubMedGoogle Scholar
  28. Greendale GA, Palla SL, Ursin G et al (2005) The association of endogenous sex steroids and sex steroid binding proteins with mammographic density: results from the Postmenopausal Estrogen/Progestin Interventions Mammographic Density Study. Am J Epidemiol 162(9):826–834CrossRefPubMedGoogle Scholar
  29. Greendale GA, Reboussin BA, Slone S, Wasilauskas C, Pike MC, Ursin G (2003) Postmenopausal hormone therapy and change in mammographic density. J Natl Cancer Inst 95(1):30–37CrossRefPubMedGoogle Scholar
  30. Hankinson SE, Willett WC, Michaud DS et al (1999) Plasma prolactin levels and subsequent risk of breast cancer in postmenopausal women. J Natl Cancer Inst 91(7):629–634CrossRefPubMedGoogle Scholar
  31. Hofling M, Lundstrom E, Azavedo E, Svane G, Hirschberg AL, von Schoultz B (2007) Testosterone addition during menopausal hormone therapy: effects on mammographic breast density. Climacteric 10(2):155–163CrossRefPubMedGoogle Scholar
  32. Hunter DJ, Willett WC (1993) Diet, body size, and breast cancer. Epidemiol Rev 15(1):110–132PubMedGoogle Scholar
  33. Johansson H, Gandini S, Bonanni B, Marieet F, Guerrieri-Gonzaga A, Serrano D et al (2008) Relationships between circulating hormone levels, mammographic percent density and breast cancer risk factors in postmenopausal women. Breast Cancer Res Treat 108:57–67CrossRefPubMedGoogle Scholar
  34. Kelsey JL, Gammon MD, John ES (1993) Reproductive factors and breast cancer. Epidemiol Rev 15(1):36–47PubMedGoogle Scholar
  35. Kerlikowske K, Ichikawa L, Miglioretti DL et al (2007) Longitudinal measurement of clinical mammographic breast density to improve estimation of breast cancer risk. J Natl Cancer Inst 99(5):386–395CrossRefPubMedGoogle Scholar
  36. Key TJ, Appleby PN, Reeves GK et al (2003) Body mass index, serum sex hormones, and breast cancer risk in postmenopausal women. J Natl Cancer Inst 95(16):1218–1226CrossRefPubMedGoogle Scholar
  37. Li T, Sun L, Miller N et al (2005) The association of measured breast tissue characteristics with mammographic density and other risk factors for breast cancer. Cancer Epidemiol Biomarkers Prev 14(2):343–349CrossRefPubMedGoogle Scholar
  38. Martin LJ, Boyd N (2008) Potential mechanisms of breast cancer risk associated with mammographic density: hypotheses based on epidemiological evidence. Breast Cancer Res 10(1):1–14CrossRefGoogle Scholar
  39. Maskarinec G, Meng L, Ursin G (2001) Ethnic differences in mammographic densities. Int J Epidemiol 30(5):959–965CrossRefPubMedGoogle Scholar
  40. Maskarinec G, Pagano I, Lurie G, Kolonel LN (2006) A longitudinal investigation of mammographic density: the multiethnic cohort. Cancer Epidemiol Biomarkers Prev 15(4):732–739CrossRefPubMedGoogle Scholar
  41. McCormack VA, dos Santos Silva I (2006) Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev 15(6):1159–1169CrossRefPubMedGoogle Scholar
  42. McTiernan A, Martin DF, Peck JD et al (2005) Estrogen-plus-progestin use and mammographic density in postmenopausal women: women’s health initiative randomized trial. J Natl Cancer Inst 97(18):1366–1376CrossRefPubMedGoogle Scholar
  43. Muir C, Waterhouse T, Mack J, Powell S, Whelan S (1992) Cancer incidence in five continents. Volume V1 ed. IARC Scientific Publication, LyonGoogle Scholar
  44. Noh JJ, Maskarinec G, Pagano I, Cheung LW, Stanczyk FZ (2006) Mammographic densities and circulating hormones: a cross-sectional study in premenopausal women. Breast 15(1):20–28CrossRefPubMedGoogle Scholar
  45. Pike MC, Krailo MD, Henderson BE, Casagrande JT, Hoel DG (1983) “Hormonal” risk factors, “breast tissue age” and the age-incidence of breast cancer. Nature 303(5920):767–770CrossRefPubMedGoogle Scholar
  46. Pisano ED, Gatsonis C, Hendrick E et al (2005) Diagnostic performance of digital versus film mammography for breast-cancer screening. N Engl J Med 353(17):1773–1783CrossRefPubMedGoogle Scholar
  47. Prentice RL (1988) Surrogate endpoints in clinical trials: definition and operational criteria. Stat Med 8(4):431–440CrossRefGoogle Scholar
  48. Renehan AG, Harvie M, Howell A (2006) Insulin-like growth factor (IGF)-I, IGF binding protein-3, and breast cancer risk: eight years on. Endocr Relat Cancer 13(2):273–278CrossRefPubMedGoogle Scholar
  49. Rosner B, Colditz G (1996) Nurses’ health study: log-incidence mathematical model of breast cancer incidence. J Natl Cancer Inst 88(6):359–364CrossRefPubMedGoogle Scholar
  50. Schatzkin A, Gail M (2002) The promise and peril of surrogate end points in cancer research. Nat Rev 2(1):19–27Google Scholar
  51. Spicer DV, Ursin G, Parisky YR et al (1994) Changes in mammographic densities induced by a hormonal contraceptive designed to reduce breast cancer risk. J Natl Cancer Inst 86(6):431–436CrossRefPubMedGoogle Scholar
  52. Tamimi RM, Byrne C, Colditz GA, Hankinson SE (2007) Endogenous hormone levels, mammographic density, and subsequent risk of breast cancer in postmenopausal women. J Natl Cancer Inst 99(15):1178–1187CrossRefPubMedGoogle Scholar
  53. Tamimi RM, Hankinson SE, Colditz GA, Byrne C (2005) Endogenous sex hormone levels and mammographic density among postmenopausal women. Cancer Epidemiol Biomarkers Prev 14(11 Pt 1):2641–2647CrossRefPubMedGoogle Scholar
  54. Tworoger SS, Eliassen AH, Sluss P, Hankinson SE (2007) A prospective study of plasma prolactin concentrations and risk of premenopausal and postmenopausal breast cancer. J Clin Oncol 25(12):1482–1488CrossRefPubMedGoogle Scholar
  55. Ursin G, Wu AH, Bernstein L et al (2003) Mammographic density and breast cancer in three ethnic groups. Cancer Epidemiol Biomarkers Prev 12(4):332–338PubMedGoogle Scholar
  56. Vachon CM, Kuni CC, Anderson K (2000) Association of mammographically defined percent breast density with epidemiologic risk factors for breast cancer (United States). Cancer Causes Control 11(7):653–662CrossRefPubMedGoogle Scholar
  57. Vachon CM, Ingle JN, Suman VJ, Scott CG, Gottardt H, Olson JE, Goss PE (2007) Pilot study of the impact of letrozole vs. placebo on breast density in women completing 5 years of tamoxifen. Breast Apr;16(2):204–210CrossRefPubMedGoogle Scholar
  58. Vachon CM, Pankratz VS, Scott CG et al (2007) Longitudinal trends in mammographic percent density and breast cancer risk. Cancer Epidemiol Biomarkers Prev 16(5):921–928CrossRefPubMedGoogle Scholar
  59. Verheus M, Peeters PHM, van Noord PAH, van der Schouw YT, Grobbee DE, van Gils CH (2007) No relationship between circulating levels of sex steroids and mammographic breast density: the Prospect-EPIC cohort. Breast Cancer Res 9(4):R53CrossRefPubMedGoogle Scholar
  60. Veronesi U, Boyle P, Goldhirsch A, Orecchia R, Viale G (2005) Breast cancer. Lancet 365(9472):1727–1741CrossRefPubMedGoogle Scholar
  61. Vogel VG, Costantino JP, Wickerham DL et al (2006) Effects of tamoxifen vs raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P-2 trial. JAMA 295(23):2727–2741CrossRefPubMedGoogle Scholar
  62. Warren R, Skinner J, Sala E et al (2006) Associations among mammographic density, circulating sex hormones, and polymorphisms in sex hormone metabolism genes in postmenopausal women. Cancer Epidemiol Biomarkers Prev 15(8):1502–1508CrossRefPubMedGoogle Scholar
  63. Wolfe JN (1976) Breast patterns as an index of risk for developing breast cancer. AJR Am J Roentgenol 126(6):1130–1137PubMedGoogle Scholar
  64. Wolfe JN (1976) Risk for breast cancer development determined by mammographic parenchymal pattern. Cancer 37(5):2486–2492CrossRefPubMedGoogle Scholar
  65. Ziv E, Shepherd J, Smith-Bindman R, Kerlikowske K (2005) Mammographic breast density and family history of breast cancer. J Natl Cancer Inst 95(7):556–558Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Norman F Boyd
    • 1
  • Lisa J Martin
    • 1
  • Salomon Minkin
    • 1
  1. 1.Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Princess Margaret HospitalTorontoCanada

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