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Breast Cancer Research and Treatment

, Volume 150, Issue 1, pp 181–189 | Cite as

Mammographic breast density and breast cancer risk: interactions of percent density, absolute dense, and non-dense areas with breast cancer risk factors

  • Lusine Yaghjyan
  • Graham A. Colditz
  • Bernard Rosner
  • Rulla M. TamimiEmail author
Epidemiology

Abstract

We investigated if associations of breast density and breast cancer differ according to the level of other known breast cancer risk factors, including body mass index (BMI), age at menarche, parity, age at first child’s birth, age at menopause, alcohol consumption, a family history of breast cancer, a history of benign breast disease, and physical activity. This study included 1,044 postmenopausal incident breast cancer cases diagnosed within the Nurses’ Health Study cohort and 1,794 matched controls. Percent breast density, absolute dense, and non-dense areas were measured from digitized film images with computerized techniques. Information on breast cancer risk factors was obtained prospectively from biennial questionnaires. Percent breast density was more strongly associated with breast cancer risk in current postmenopausal hormone users (≥50 vs. 10 %: OR 5.34, 95 % CI 3.36–8.49) as compared to women with past (OR 2.69, 95 % CI 1.32–5.49) or no hormone history (OR 2.57, 95 % CI 1.18–5.60, p-interaction = 0.03). Non-dense area was inversely associated with breast cancer risk in parous women, but not in women without children (p-interaction = 0.03). Associations of density with breast cancer risk did not differ by the levels of BMI, age at menarche, parity, age at first child’s birth, age at menopause, alcohol consumption, a family history of breast cancer, a history of benign breast disease, and physical activity. Women with dense breasts, who currently use menopausal hormone therapy are at a particularly high risk of breast cancer. Most breast cancer risk factors do not modify the association between mammographic breast density and breast cancer risk.

Keywords

Breast density Breast cancer risk Risk factors Parity Menopausal hormone use Interactions 

Notes

Acknowledgments

We would like to thank the participants and staff of the Nurses’ Health Study for their valuable contributions as well as the following state cancer registries for their help: AL, AZ, AR, CA, CO, CT, DE, FL, GA, ID, IL, IN, IA, KY, LA, ME, MD, MA, MI, NE, NH, NJ, NY, NC, ND, OH, OK, OR, PA, RI, SC, TN, TX, VA, WA, WY. The authors assume full responsibility for analyses and interpretation of these data. Financial support was received from Public Health Service Grants CA131332, CA186107, CA087969, CA186107, UM1 from the National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Avon Foundation for Women, Susan G. Komen for the Cure®, and Breast Cancer Research Foundation. Dr. Colditz is supported in part by an American Cancer Society Cissy Hornung Clinical Research Professorship.

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Supplementary material 1 (DOCX 18 kb)
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Supplementary material 2 (DOCX 24 kb)
10549_2015_3286_MOESM3_ESM.docx (22 kb)
Supplementary material 3 (DOCX 23 kb)

References

  1. 1.
    Boyd NF, Rommens JM, Vogt K, Lee V, Hopper JL, Yaffe MJ, Paterson AD (2005) Mammographic breast density as an intermediate phenotype for breast cancer. Lancet Oncol 6(10):798–808CrossRefPubMedGoogle Scholar
  2. 2.
    Ginsburg OM, Martin LJ, Boyd NF (2008) Mammographic density, lobular involution, and risk of breast cancer. Br J Cancer 99(9):1369–1374CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    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
  4. 4.
    Harvey JA, Bovbjerg VE (2004) Quantitative assessment of mammographic breast density: relationship with breast cancer risk. Radiology 230(1):29–41CrossRefPubMedGoogle Scholar
  5. 5.
    Boyd NF, Byng JW, Jong RA, Fishell EK, Little LE, Miller AB, Lockwood GA, Tritchler DL, Yaffe MJ (1995) Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian National Breast screening Study. J Natl Cancer Inst 87(9):670–675CrossRefPubMedGoogle Scholar
  6. 6.
    Byrne C, Schairer C, Wolfe J, Parekh N, Salane M, Brinton LA, Hoover R, Haile R (1995) Mammographic features and breast cancer risk: effects with time, age, and menopause status. J Natl Cancer Inst 87(21):1622–1629CrossRefPubMedGoogle Scholar
  7. 7.
    Pettersson A, Hankinson S, Willett W, Lagiou P, Trichopoulos D, Tamimi R (2011) Nondense mammographic area and risk of breast cancer. Breast Cancer Res 13(5):R100CrossRefPubMedCentralPubMedGoogle Scholar
  8. 8.
    Aitken Z, McCormack VA, Highnam RP, Martin L, Gunasekara A, Melnichouk O, Mawdsley G, Peressotti C, Yaffe M, Boyd NF, dos Santos Silva I (2010) Screen-film mammographic density and breast cancer risk: a comparison of the volumetric standard mammogram form and the interactive threshold measurement methods. Cancer Epidemiol Biomark Prev 19(2):418–428CrossRefGoogle Scholar
  9. 9.
    Stone J, Ding J, Warren RM, Duffy SW, Hopper JL (2010) Using mammographic density to predict breast cancer risk: dense area or percentage dense area. Breast Cancer Res 12(6):R97CrossRefPubMedCentralPubMedGoogle Scholar
  10. 10.
    Ursin G, Ma H, Wu AH, Bernstein L, Salane M, Parisky YR, Astrahan M, Siozon CC, Pike MC (2003) Mammographic density and breast cancer in three ethnic groups. Cancer Epidemiol Biomark Prev 12(4):332–338Google Scholar
  11. 11.
    Maskarinec G, Pagano I, Lurie G, Wilkens LR, Kolonel LN (2005) Mammographic density and breast cancer risk. Am J Epidemiol 162(8):743–752CrossRefPubMedGoogle Scholar
  12. 12.
    Boyd N, Martin L, Gunasekara A, Melnichouk O, Maudsley G, Peressotti C, Yaffe M, Minkin S (2009) Mammographic density and breast cancer risk: evaluation of a novel method of measuring breast tissue volumes. Cancer Epidemiol Biomark Prev 18(6):1754–1762CrossRefGoogle Scholar
  13. 13.
    Vachon CM, Brandt KR, Ghosh K, Scott CG, Maloney SD, Carston MJ, Pankratz VS, Sellers TA (2007) Mammographic breast density as a general marker of breast cancer risk. Cancer Epidemiol Biomark Prev 16(1):43–49CrossRefGoogle Scholar
  14. 14.
    Lokate M, Peeters PH, Peelen LM, Haars G, Veldhuis WB, van Gils CH (2011) Mammographic density and breast cancer risk: the role of the fat surrounding the fibroglandular tissue. Breast Cancer Res 13(5):R103CrossRefPubMedCentralPubMedGoogle Scholar
  15. 15.
    Pettersson A, Graff RE, Ursin G, Santos Silva ID, McCormack V, Baglietto L, Vachon C, Bakker MF, Giles GG, Chia KS, Czene K, Eriksson L, Hall P, Hartman M, Warren RM, Hislop G, Chiarelli AM, Hopper JL, Krishnan K, Li J, Li Q, Pagano I, Rosner BA, Wong CS, Scott C, Stone J, Maskarinec G, Boyd NF, van Gils CH, Tamimi RM (2014) Mammographic density phenotypes and risk of breast cancer: a meta-analysis. J Natl Cancer InstGoogle Scholar
  16. 16.
    Wong CS, Lim GH, Gao F, Jakes RW, Offman J, Chia KS, Duffy SW (2011) Mammographic density and its interaction with other breast cancer risk factors in an Asian population. Br J Cancer 104(5):871–874CrossRefPubMedCentralPubMedGoogle Scholar
  17. 17.
    Duffy SW, Jakes RW, Ng FC, Gao F (2004) Interaction of dense breast patterns with other breast cancer risk factors in a case–control study. Br J Cancer 91(2):233–236PubMedCentralPubMedGoogle Scholar
  18. 18.
    Woolcott CG, Koga K, Conroy SM, Byrne C, Nagata C, Ursin G, Vachon CM, Yaffe MJ, Pagano I, Maskarinec G (2012) Mammographic density, parity and age at first birth, and risk of breast cancer: an analysis of four case–control studies. Breast Cancer Res Treat 132(3):1163–1171CrossRefPubMedCentralPubMedGoogle Scholar
  19. 19.
    van Gils CH, Hendriks JH, Otten JD, Holland R, Verbeek AL (2000) Parity and mammographic breast density in relation to breast cancer risk: indication of interaction. Eur J Cancer Prev 9(2):105–111CrossRefPubMedGoogle Scholar
  20. 20.
    Martin LJ, Melnichouk O, Guo H, Chiarelli AM, Hislop TG, Yaffe MJ, Minkin S, Hopper JL, Boyd NF (2010) Family history, mammographic density, and risk of breast cancer. Cancer Epidemiol Biomark Prev 19(2):456–463CrossRefGoogle Scholar
  21. 21.
    Yaghjyan L, Colditz GA, Rosner B, Tamimi RM (2012) Mammographic breast density and breast cancer risk by menopausal status, postmenopausal hormone use and a family history of breast cancer. Cancer Causes Control 23(5):785–790CrossRefPubMedGoogle Scholar
  22. 22.
    Colditz GA, Hankinson SE (2005) The Nurses’ Health Study: lifestyle and health among women. Nat Rev Cancer 5(5):388–396CrossRefPubMedGoogle Scholar
  23. 23.
    McCormack VA, dos Santos Silva I (2006) Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomark Prev 15(6):1159–1169CrossRefGoogle Scholar
  24. 24.
    Kerlikowske K, Cook AJ, Buist DS, Cummings SR, Vachon C, Vacek P, Miglioretti DL (2010) Breast cancer risk by breast density, menopause, and postmenopausal hormone therapy use. J Clin Oncol 28(24):3830–3837CrossRefPubMedCentralPubMedGoogle Scholar
  25. 25.
    Ghosh K, Hartmann LC, Reynolds C, Visscher DW, Brandt KR, Vierkant RA, Scott CG, Radisky DC, Sellers TA, Pankratz VS, Vachon CM (2010) Association between mammographic density and age-related lobular involution of the breast. J Clin Oncol 28(13):2207–2212CrossRefPubMedCentralPubMedGoogle Scholar
  26. 26.
    Byng JW, Boyd NF, Little L, Lockwood G, Fishell E, Jong RA, Yaffe MJ (1996) Symmetry of projection in the quantitative analysis of mammographic images. Eur J Cancer Prev 5(5):319–327CrossRefPubMedGoogle Scholar
  27. 27.
    Yaghjyan L, Colditz GA, Collins LC, Schnitt SJ, Rosner B, Vachon C, Tamimi RM (2011) Mammographic breast density and subsequent risk of breast cancer in postmenopausal women according to tumor characteristics. J Natl Cancer Inst 103(15):1179–1189CrossRefPubMedCentralPubMedGoogle Scholar
  28. 28.
    Rosner B, Colditz GA (1996) Nurses’ health study: log-incidence mathematical model of breast cancer incidence. J Natl Cancer Inst 88(6):359–364CrossRefPubMedGoogle Scholar
  29. 29.
    Conner P, Svane G, Azavedo E, Soderqvist G, Carlstrom K, Graser T, Walter F, von Schoultz B (2004) Mammographic breast density, hormones, and growth factors during continuous combined hormone therapy. Fertil Steril 81(6):1617–1623CrossRefPubMedGoogle Scholar
  30. 30.
    Greendale GA, Palla SL, Ursin G, Laughlin GA, Crandall C, Pike MC, Reboussin BA (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
  31. 31.
    Pettersen PC, Raundahl J, Loog M, Nielsen M, Tanko LB, Christiansen C (2008) Parallel assessment of the impact of different hormone replacement therapies on breast density by radiologist- and computer-based analyses of mammograms. Climacteric 11(2):135–143CrossRefPubMedGoogle Scholar
  32. 32.
    Vachon CM, Sellers TA, Vierkant RA, Wu FF, Brandt KR (2002) Case-control study of increased mammographic breast density response to hormone replacement therapy. Cancer Epidemiol Biomark Prev 11(11):1382–1388Google Scholar
  33. 33.
    Boyd NF, Martin LJ, Li Q, Sun L, Chiarelli AM, Hislop G, Yaffe MJ, Minkin S (2006) Mammographic density as a surrogate marker for the effects of hormone therapy on risk of breast cancer. Cancer Epidemiol Biomark Prev 15(5):961–966CrossRefGoogle Scholar
  34. 34.
    Li T, Sun L, Miller N, Nicklee T, Woo J, Hulse-Smith L, Tsao MS, Khokha R, Martin L, Boyd N (2005) The association of measured breast tissue characteristics with mammographic density and other risk factors for breast cancer. Cancer Epidemiol Biomark Prev 14(2):343–349CrossRefGoogle Scholar
  35. 35.
    van Kruijsdijk RCM, van der Wall E, Visseren FLJ (2009) Obesity and cancer: the role of dysfunctional adipose tissue. Cancer Epidemiol Biomark Prev 18(10):2569–2578CrossRefGoogle Scholar
  36. 36.
    Ghosh K, Vachon CM, Pankratz VS, Vierkant RA, Anderson SS, Brandt KR, Visscher DW, Frost MH, Hartmann LC (2010) Independent association of lobular involution and mammographic breast density with breast cancer risk. J Natl Cancer Inst 102(22):1716–1723CrossRefPubMedCentralPubMedGoogle Scholar
  37. 37.
    Lambe M, Hsieh CC, Chan HW, Ekbom A, Trichopoulos D, Adami HO (1996) Parity, age at first and last birth, and risk of breast cancer: a population-based study in Sweden. Breast Cancer Res Treat 38(3):305–311CrossRefPubMedGoogle Scholar
  38. 38.
    Ewertz M, Duffy SW, Adami HO, Kvale G, Lund E, Meirik O, Mellemgaard A, Soini I, Tulinius H (1990) Age at first birth, parity and risk of breast cancer: a meta-analysis of 8 studies from the Nordic countries. Int J Cancer 46(4):597–603CrossRefPubMedGoogle Scholar
  39. 39.
    Colditz GA (1993) Epidemiology of breast cancer. Findings from the nurses’ health study. Cancer 71(4 Suppl):1480–1489CrossRefPubMedGoogle Scholar
  40. 40.
    Haars G, van Noord PAH, van Gils CH, Grobbee DE, Peeters PHM (2005) Measurements of breast density: no ratio for a ratio. Cancer Epidemiol Biomark Prev 14(11):2634–2640CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Lusine Yaghjyan
    • 1
  • Graham A. Colditz
    • 2
    • 3
  • Bernard Rosner
    • 4
  • Rulla M. Tamimi
    • 4
    Email author
  1. 1.Department of Epidemiology, College of Public Health and Health Professions and College of MedicineUniversity of FloridaGainesvilleUSA
  2. 2.Department of SurgeryWashington University in St. Louis School of MedicineSt. LouisUSA
  3. 3.Institute for Public HealthWashington University in St. LouisSt. LouisUSA
  4. 4.Channing Division of Network Medicine, Department of MedicineBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA

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