Cancer Causes & Control

, Volume 26, Issue 4, pp 621–626 | Cite as

Mammographic density and breast cancer risk by family history in women of white and Asian ancestry

  • Gertraud MaskarinecEmail author
  • Kaylae L. Nakamura
  • Christy G. Woolcott
  • Shannon M. Conroy
  • Celia Byrne
  • Chisato Nagata
  • Giske Ursin
  • Celine M. Vachon
Original paper



Mammographic density, i.e., the radiographic appearance of the breast, is a strong predictor of breast cancer risk. To determine whether the association of breast density with breast cancer is modified by a first-degree family history of breast cancer (FHBC) in women of white and Asian ancestry, we analyzed data from four case–control studies conducted in the USA and Japan.


The study population included 1,699 breast cancer cases and 2,422 controls, of whom 45 % reported white (N = 1,849) and 40 % Asian (N = 1,633) ancestry. To standardize mammographic density assessment, a single observer re-read all mammograms using one type of interactive thresholding software. Logistic regression was applied to estimate odds ratios (OR) while adjusting for confounders.


Overall, 496 (12 %) of participants reported a FHBC, which was significantly associated with breast cancer risk in the adjusted model (OR 1.51; 95 % CI 1.23–1.84). There was a statistically significant interaction on a multiplicative scale between FHBC and continuous percent density (per 10 % density: p = 0.03). The OR per 10 % increase in percent density was higher among women with a FHBC (OR 1.30; 95 % CI 1.13–1.49) than among those without a FHBC (OR 1.14; 1.09–1.20). This pattern was apparent in whites and Asians. The respective ORs were 1.45 (95 % CI 1.17–1.80) versus 1.22 (95 % CI 1.14–1.32) in whites, whereas the values in Asians were only 1.24 (95 % CI 0.97–1.58) versus 1.09 (95 % CI 1.00–1.19).


These findings support the hypothesis that women with a FHBC appear to have a higher risk of breast cancer associated with percent mammographic density than women without a FHBC.


Breast neoplasms Mammographic density Family history Epidemiology Risk factor Effect modification 



Body mass index


Confidence interval


Family history of breast cancer


Hormone therapy


Odds ratio



This research was supported by the National Cancer Institute, US Department of Health and Human Services, Grant no. R03 CA 135699. CGW and SMC were supported during the work on this Project by postdoctoral fellowships on grant R25 CA 90956.

Conflict of interest

The authors declare no conflict of interest.


  1. 1.
    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 23:785–790CrossRefPubMedGoogle Scholar
  2. 2.
    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 15:1159–1169CrossRefGoogle Scholar
  3. 3.
    Martin LJ, Melnichouk O, Guo H et al (2010) Family history, mammographic density and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 19:456–463CrossRefPubMedGoogle Scholar
  4. 4.
    Colditz GA, Baer HJ, Tamimi RM (2006) Breast cancer. In: Schottenfeld D, Fraumeni JF (eds) Cancer epidemiology and prevention. Oxford University Press, New York, pp 189–201Google Scholar
  5. 5.
    Tice JA, Cummings SR, Ziv E, Kerlikowske K (2005) Mammographic breast density and the gail model for breast cancer risk prediction in a screening population. Breast Cancer Res Treat 94:115–122CrossRefPubMedGoogle Scholar
  6. 6.
    Vachon CM, van Gils CH, Sellers TA et al (2007) Mammographic density, breast cancer risk and risk prediction. Breast Cancer Res 9:217CrossRefPubMedCentralPubMedGoogle Scholar
  7. 7.
    Sestak I, Cuzick J (2015) Update on breast cancer risk prediction and prevention. Curr Opin Obstet Gynecol 27:92–97CrossRefPubMedGoogle Scholar
  8. 8.
    Vachon CM, Scott CG, Fasching PA et al (2012) Common breast cancer susceptibility variants in LSP1 and RAD51L1 are associated with mammographic density measures that predict breast cancer risk. Cancer Epidemiol Biomarkers Prev 21:1156–1166CrossRefPubMedCentralPubMedGoogle Scholar
  9. 9.
    Ziv E, Shepherd J, Smith-Bindman R, Kerlikowske K (2003) Mammographic breast density and family history of breast cancer. J Natl Cancer Inst 95:556–558CrossRefPubMedGoogle Scholar
  10. 10.
    Saftlas AF, Wolfe JN, Hoover RN et al (1989) Mammographic parenchymal patterns as indicators of breast cancer risk. Am J Epidemiol 129:518–526PubMedGoogle Scholar
  11. 11.
    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 87:1622–1629CrossRefPubMedGoogle Scholar
  12. 12.
    Brisson J (1991) Family history of breast cancer, mammographic features of breast tissue, and breast cancer risk. Epidemiology 2:440–444CrossRefPubMedGoogle Scholar
  13. 13.
    Mitchell G, Antoniou AC, Warren R et al (2006) Mammographic density and breast cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer Res 66:1866–1872CrossRefPubMedGoogle Scholar
  14. 14.
    Conroy SM, Woolcott CG, Koga KR et al (2012) Mammographic density and risk of breast cancer by adiposity: An analysis of four case–control studies. Int J Cancer 130:1915–1924CrossRefPubMedCentralPubMedGoogle Scholar
  15. 15.
    Ursin G, Ma H, Wu AH et al (2003) Mammographic density and breast cancer in three ethnic groups. Cancer Epidemiol Biomarkers Prev 12:332–338PubMedGoogle Scholar
  16. 16.
    Maskarinec G, Pagano I, Lurie G, Wilkens LR, Kolonel LN (2005) Mammographic density and breast cancer risk: the multiethnic cohort study. Am J Epidemiol 162:743–752CrossRefPubMedGoogle Scholar
  17. 17.
    Nagata C, Matsubara T, Fujita H et al (2005) Mammographic density and the risk of breast cancer in Japanese women. Br J Cancer 92:2102–2106CrossRefPubMedCentralPubMedGoogle Scholar
  18. 18.
    Vachon CM, Brandt KR, Ghosh K et al (2007) Mammographic breast density as a general marker of breast cancer risk. Cancer Epidemiol Biomarkers Prev 16:43–49CrossRefPubMedGoogle Scholar
  19. 19.
    Pollan M, Lope V, Miranda-Garcia J et al (2012) Adult weight gain, fat distribution and mammographic density in Spanish pre- and post-menopausal women (DDM-Spain). Breast Cancer Res Treat 134:823–838CrossRefPubMedCentralPubMedGoogle Scholar
  20. 20.
    Crest AB, Aiello EJ, Anderson ML, Buist DS (2006) Varying levels of family history of breast cancer in relation to mammographic breast density (United States). Cancer Causes Control 17:843–850CrossRefPubMedGoogle Scholar
  21. 21.
    Helvie MA, Roubidoux MA, Weber BL, Merajver SD (1997) Mammography of breast carcinoma in women who have mutations of the breast cancer gene BRCA1: initial experience. AJR Am J Roentgenol 168:1599–1602CrossRefPubMedGoogle Scholar
  22. 22.
    Gierach GL, Loud JT, Chow CK et al (2010) Mammographic density does not differ between unaffected BRCA1/2 mutation carriers and women at low-to-average risk of breast cancer. Breast Cancer Res Treat 123:245–255CrossRefPubMedCentralPubMedGoogle Scholar
  23. 23.
    Boyd NF, Dite GS, Stone J et al (2002) Heritability of mammographic density, a risk factor for breast cancer. N Engl J Med 347:886–894CrossRefPubMedGoogle Scholar
  24. 24.
    Kataoka M, Antoniou A, Warren R et al (2009) Genetic models for the familial aggregation of mammographic breast density. Cancer Epidemiol Biomarkers Prev 18:1277–1284CrossRefPubMedGoogle Scholar
  25. 25.
    Nguyen TL, Schmidt DF, Makalic E et al (2013) Explaining variance in the cumulus mammographic measures that predict breast cancer risk: a twins and sisters study. Cancer Epidemiol Biomarkers Prev 22:2395–2403CrossRefPubMedGoogle Scholar
  26. 26.
    Ursin G, Lillie EO, Lee E et al (2009) The relative importance of genetics and environment on mammographic density. Cancer Epidemiol Biomarkers Prev 18:102–112CrossRefPubMedGoogle Scholar
  27. 27.
    Ellingjord-Dale M, Grotmol T, Lee E et al (2014) Breast Cancer Susceptibility Variants and Mammographic Density Phenotypes in Norwegian Postmenopausal Women. Cancer Epidemiol Biomarkers Prev 23:1752–1763CrossRefPubMedGoogle Scholar
  28. 28.
    Lindstrom S, Vachon CM, Li J et al (2011) Common variants in ZNF365 are associated with both mammographic density and breast cancer risk. Nat Genet 43:185–187CrossRefPubMedCentralPubMedGoogle Scholar
  29. 29.
    Varghese JS, Thompson DJ, Michailidou K et al (2012) Mammographic breast density and breast cancer: evidence of a shared genetic basis. Cancer Res 72:1478–1484CrossRefPubMedCentralPubMedGoogle Scholar
  30. 30.
    Ziogas A, Anton-Culver H (2003) Validation of family history data in cancer family registries. Am J Prev Med 24:190–198CrossRefPubMedGoogle Scholar
  31. 31.
    Ozanne EM, O’Connell A, Bouzan C et al (2012) Bias in the reporting of family history: implications for clinical care. J Genet Couns 21:547–556CrossRefPubMedGoogle Scholar
  32. 32.
    Kerber RA, Slattery ML (1997) Comparison of self-reported and database-linked family history of cancer data in a case–control study. Am J Epidemiol 146:244–248CrossRefPubMedGoogle Scholar
  33. 33.
    Woolcott CG, Conroy SM, Nagata C et al (2014) Methods for assessing and representing mammographic density: an analysis of 4 case–control studies. Am J Epidemiol 179:236–244CrossRefPubMedCentralPubMedGoogle Scholar
  34. 34.
    Lindstrom S, Thompson DJ, Paterson AD et al (2014) Genome-wide association study identifies multiple loci associated with both mammographic density and breast cancer risk. Nat Commun 5:5303CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Gertraud Maskarinec
    • 1
    Email author
  • Kaylae L. Nakamura
    • 1
  • Christy G. Woolcott
    • 2
  • Shannon M. Conroy
    • 3
  • Celia Byrne
    • 4
  • Chisato Nagata
    • 5
  • Giske Ursin
    • 6
  • Celine M. Vachon
    • 7
  1. 1.University of Hawaii Cancer CenterHonoluluUSA
  2. 2.Departments of Obstetrics and Gynaecology and PediatricsDalhousie UniversityHalifaxCanada
  3. 3.Department of Public Health SciencesUniversity of California Davis School of MedicineDavisUSA
  4. 4.Uniformed Services University of the Health SciencesBethesdaUSA
  5. 5.Gifu University Graduate School of MedicineGifu-shiJapan
  6. 6.Cancer Registry of NorwayOsloNorway
  7. 7.Mayo ClinicRochesterUSA

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