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Mammographic density does not differ between unaffected BRCA1/2 mutation carriers and women at low-to-average risk of breast cancer

  • Epidemiology
  • Published:
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Abstract

Elevated mammographic density (MD) is one of the strongest risk factors for sporadic breast cancer. Epidemiologic evidence suggests that MD is, in part, genetically determined; however, the relationship between MD and BRCA1/2 mutation status is equivocal. We compared MD in unaffected BRCA1/2 mutation carriers enrolled in the U.S. National Cancer Institute’s Clinical Genetics Branch’s Breast Imaging Study (n = 143) with women at low-to-average breast cancer risk enrolled in the same study (n = 29) or the NCI/National Naval Medical Center’s Susceptibility to Breast Cancer Study (n = 90). The latter were BRCA mutation-negative members of mutation-positive families or women with no prior breast cancer, a Pedigree Assessment Tool score <8 (i.e., low risk of a hereditary breast cancer syndrome) and a Gail score <1.67. A single experienced mammographer measured MD using a computer-assisted thresholding method. We collected standard breast cancer risk factor information in both studies. Unadjusted mean percent MD was higher in women with BRCA1/2 mutations compared with women at low-to-average breast cancer risk (37.3% vs. 33.4%; P = 0.04), but these differences disappeared after adjusting for age and body mass index (34.9% vs. 36.3%; P = 0.43). We explored age at menarche, nulliparity, age at first birth, menopausal status, number of breast biopsies, and exposure to exogenous hormonal agents as potential confounders of the MD and BRCA1/2 association. Taking these factors into account did not significantly alter the results of the age/body mass index-adjusted analysis. Our results do not provide support for an independent effect of BRCA1/2 mutation status on mammographic density.

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Abbreviations

ANOVA:

Analysis of variance

BI-RADS:

Breast Imaging Reporting and Data System

BMI:

Body mass index

ICC:

Intra-class correlation coefficient

IRB:

Institutional review board

MD:

Mammographic density

NCI:

National Cancer Institute

NIH:

National Institutes of Health

NNMC:

National Naval Medical Center

PAT:

Pedigree Assessment Tool

References

  1. Boyd NF, Lockwood GA, Byng JW, Tritchler DL, Yaffe MJ (1998) Mammographic densities and breast cancer risk. Cancer Epidemiol Biomarkers Prev 7(12):1133–1144

    CAS  PubMed  Google Scholar 

  2. Boyd NF, Guo H, Martin LJ, Sun L, Stone J, Fishell E, Jong RA, Hislop G, Chiarelli A, Minkin S, Yaffe MJ (2007) Mammographic density and the risk and detection of breast cancer. N Engl J Med 356(3):227–236

    Article  CAS  PubMed  Google Scholar 

  3. 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):1622–1629

    Article  CAS  PubMed  Google Scholar 

  4. Boyd NF, Lockwood GA, Martin LJ, Byng JW, Yaffe MJ, Tritchler DL (2001) Mammographic density as a marker of susceptibility to breast cancer: a hypothesis. IARC Sci Publ 154:163–169

    Google Scholar 

  5. Martin LJ, Boyd NF (2008) Mammographic density—potential mechanisms of breast cancer risk associated with mammographic density: hypotheses based on epidemiological evidence. Breast Cancer Res 10(1):201

    Article  PubMed  CAS  Google Scholar 

  6. Kelemen LE, Sellers TA, Vachon CM (2008) Can genes for mammographic density inform cancer aetiology? Nat Rev Cancer 8(10):812–823

    Article  CAS  PubMed  Google Scholar 

  7. Wilkinson E, Clopton C, Gordonson J, Green R, Hill A, Pike MC (1977) Mammographic parenchymal pattern and the risk of breast cancer. J Natl Cancer Inst 59(5):1397–1400

    CAS  PubMed  Google Scholar 

  8. Krook PM, Carlile T, Bush W, Hall MH (1978) Mammographic parenchymal patterns as a risk indicator for prevalent and incident cancer. Cancer 41(3):1093–1097

    Article  CAS  PubMed  Google Scholar 

  9. Ernster VL, Sacks ST, Peterson CA, Schweitzer RJ (1980) Mammographic parenchymal patterns and risk factors for breast cancer. Radiology 134(3):617–620

    CAS  PubMed  Google Scholar 

  10. Buchanan JB, Weisberg BF, Sandoz JP, Gray LA Sr, Bland KI (1981) Selected prognostic variables for mammographic parenchymal patterns. Cancer 47(9):2135–2137

    Article  CAS  PubMed  Google Scholar 

  11. de Waard F, Rombach JJ, Collette HJ, Slotboom B (1984) Breast cancer risk associated with reproductive factors and breast parenchymal patterns. J Natl Cancer Inst 72(6):1277–1282

    PubMed  Google Scholar 

  12. Brisson J, Sadowsky NL, Twaddle JA, Morrison AS, Cole P, Merletti F (1982) The relation of mammographic features of the breast to breast cancer risk factors. Am J Epidemiol 115(3):438–443

    CAS  PubMed  Google Scholar 

  13. Saftlas AF, Wolfe JN, Hoover RN, Brinton LA, Schairer C, Salane M, Szklo M (1989) Mammographic parenchymal patterns as indicators of breast cancer risk. Am J Epidemiol 129(3):518–526

    CAS  PubMed  Google Scholar 

  14. Boyd NF, Lockwood GA, Martin LJ, Knight JA, Jong RA, Fishell E, Byng JW, Yaffe MJ, Tritchler DL (1999) Mammographic densities and risk of breast cancer among subjects with a family history of this disease. J Natl Cancer Inst 91(16):1404–1408

    Article  CAS  PubMed  Google Scholar 

  15. Ziv E, Shepherd J, Smith-Bindman R, Kerlikowske K (2003) Mammographic breast density and family history of breast cancer. J Natl Cancer Inst 95(7):556–558

    Article  PubMed  Google Scholar 

  16. 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(6):843–850

    Article  PubMed  Google Scholar 

  17. Gravelle IH, Bulstrode JC, Wang DY, Bulbrook RD, Hayward JL (1980) The relation between radiographic features and determinants of risk of breast cancer. Br J Radiol 53(626):107–113

    Article  CAS  PubMed  Google Scholar 

  18. Brisson J (1991) Family history of breast cancer, mammographic features of breast tissue, and breast cancer risk. Epidemiology 2(6):440–444

    Article  CAS  PubMed  Google Scholar 

  19. Kaufman Z, Garstin WI, Hayes R, Michell MJ, Baum M (1991) The mammographic parenchymal patterns of nulliparous women and women with a family history of breast cancer. Clin Radiol 43(6):385–388

    Article  CAS  PubMed  Google Scholar 

  20. Saftlas AF, Hoover RN, Brinton LA, Szklo M, Olson DR, Salane M, Wolfe JN (1991) Mammographic densities and risk of breast cancer. Cancer 67(11):2833–2838

    Article  CAS  PubMed  Google Scholar 

  21. Breuer B, Miller DG, Salane M, Wolfe JN (1992) Mammographic parenchymal patterns and family history of breast cancer. Cancer 69(2):602–603

    Article  CAS  PubMed  Google Scholar 

  22. Vachon CM, Sellers TA, Carlson EE, Cunningham JM, Hilker CA, Smalley RL, Schaid DJ, Kelemen LE, Couch FJ, Pankratz VS (2007) Strong evidence of a genetic determinant for mammographic density, a major risk factor for breast cancer. Cancer Res 67(17):8412–8418

    Article  CAS  PubMed  Google Scholar 

  23. Kataoka M, Antoniou A, Warren R, Leyland J, Brown J, Audley T, Easton D (2009) Genetic models for the familial aggregation of mammographic breast density. Cancer Epidemiol Biomarkers Prev 18(4):1277–1284

    Article  CAS  PubMed  Google Scholar 

  24. Wolfe JN, Albert S, Belle S, Salane M (1980) Familial influences on breast parenchymal patterns. Cancer 46(11):2433–2437

    Article  CAS  PubMed  Google Scholar 

  25. Pankow JS, Vachon CM, Kuni CC, King RA, Arnett DK, Grabrick DM, Rich SS, Anderson VE, Sellers TA (1997) Genetic analysis of mammographic breast density in adult women: evidence of a gene effect. J Natl Cancer Inst 89(8):549–556

    Article  CAS  PubMed  Google Scholar 

  26. Vachon CM, King RA, Atwood LD, Kuni CC, Sellers TA (1999) Preliminary sibpair linkage analysis of percent mammographic density. J Natl Cancer Inst 91(20):1778–1779

    Article  CAS  PubMed  Google Scholar 

  27. Haars G, van Noord PA, van Gils CH, Peeters PH, Grobbee DE (2004) Heritable aspects of dysplastic breast glandular tissue (DY). Breast Cancer Res Treat 87(2):149–156

    Article  CAS  PubMed  Google Scholar 

  28. Kaprio J, Alanko A, Kivisaari L, Standertskjold-Nordenstam CG (1987) Mammographic patterns in twin pairs discordant for breast cancer. Br J Radiol 60(713):459–462

    Article  CAS  PubMed  Google Scholar 

  29. Boyd NF, Dite GS, Stone J, Gunasekara A, English DR, McCredie MR, Giles GG, Tritchler D, Chiarelli A, Yaffe MJ, Hopper JL (2002) Heritability of mammographic density, a risk factor for breast cancer. N Engl J Med 347(12):886–894

    Article  PubMed  Google Scholar 

  30. 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. Am J Roentgenol 168(6):1599–1602

    CAS  Google Scholar 

  31. Chang J, Yang WT, Choo HF (1999) Mammography in Asian patients with BRCA1 mutations. Lancet 353(9169):2070–2071

    Article  CAS  PubMed  Google Scholar 

  32. Tilanus-Linthorst M, Verhoog L, Obdeijn IM, Bartels K, Menke-Pluymers M, Eggermont A, Klijn J, Meijers-Heijboer H, van der Kwast T, Brekelmans C (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(1):91–95

    Article  CAS  PubMed  Google Scholar 

  33. Hamilton LJ, Evans AJ, Wilson AR, Scott N, Cornford EJ, Pinder SE, Khan HN, Macmillan RD (2004) Breast imaging findings in women with BRCA1- and BRCA2-associated breast carcinoma. Clin Radiol 59(10):895–902

    Article  CAS  PubMed  Google Scholar 

  34. Kaas R, Kroger R, Peterse JL, Hart AA, Muller SH (2006) The correlation of mammographic-and histologic patterns of breast cancers in BRCA1 gene mutation carriers, compared to age-matched sporadic controls. Eur Radiol 16(12):2842–2848

    Article  CAS  PubMed  Google Scholar 

  35. Huo Z, Giger ML, Olopade OI, Wolverton DE, Weber BL, Metz CE, Zhong W, Cummings SA (2002) Computerized analysis of digitized mammograms of BRCA1 and BRCA2 gene mutation carriers. Radiology 225(2):519–526

    Article  PubMed  Google Scholar 

  36. Li H, Giger ML, Huo Z, Olopade OI, Lan L, Weber BL, Bonta I (2004) Computerized analysis of mammographic parenchymal patterns for assessing breast cancer risk: effect of ROI size and location. Med Phys 31(3):549–555

    Article  PubMed  Google Scholar 

  37. Mitchell G, Antoniou AC, Warren R, Peock S, Brown J, Davies R, Mattison J, Cook M, Warsi I, Evans DG, Eccles D, Douglas F, Paterson J, Hodgson S, Izatt L, Cole T, Burgess L (2006) EMBRACE collaborators, Eeles R, and Easton DF, Mammographic density and breast cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer Res 66(3):1866–1872

    Article  CAS  PubMed  Google Scholar 

  38. Loud JT, Beckjord EB, Nichols K, Peters J, Giusti R, Greene MH (2009) Tolerability of breast ductal lavage in women from families at high genetic risk of breast cancer. BMC Women’s Health 9(1):20

    Article  PubMed  Google Scholar 

  39. Loud JT, Thiebaut AC, Abati AD, Filie AC, Nichols K, Danforth D, Giusti R, Prindiville SA, Greene MH (2009) Ductal lavage in women from BRCA1/2 families: is there a future for ductal lavage in women at increased genetic risk of breast cancer? Cancer Epidemiol Biomarkers Prev 18(4):1243–1251

    Article  CAS  PubMed  Google Scholar 

  40. D’Orsi CJ, Bassett LW, Berg WA et al (2003) Breast Imaging Reporting and Data System: ACR BI-RADS-mammography, 4th edn. American College of Radiology, Reston, VA

    Google Scholar 

  41. Lam PB, Vacek PM, Geller BM, Muss HB (2000) The association of increased weight, body mass index, and tissue density with the risk of breast carcinoma in Vermont. Cancer 89(2):369–375

    Article  CAS  PubMed  Google Scholar 

  42. Vacek PM, Geller BM (2004) A prospective study of breast cancer risk using routine mammographic breast density measurements. Cancer Epidemiol Biomarkers Prev 13(5):715–722

    PubMed  Google Scholar 

  43. Ziv E, Tice J, Smith-Bindman R, Shepherd J, Cummings S, Kerlikowske K (2004) Mammographic density and estrogen receptor status of breast cancer. Cancer Epidemiol Biomarkers Prev 13(12):2090–2095

    CAS  PubMed  Google Scholar 

  44. Byng JW, Boyd NF, Fishell E, Jong RA, Yaffe MJ (1994) The quantitative analysis of mammographic densities. Phys Med Biol 39(10):1629–1638

    Article  CAS  PubMed  Google Scholar 

  45. 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 Biomarkers Prev 16(1):43–49

    Article  PubMed  Google Scholar 

  46. 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):670–675

    Article  CAS  PubMed  Google Scholar 

  47. Gail MH, Brinton LA, Byar DP, Corle DK, Green SB, Schairer C, Mulvihill JJ (1989) Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst 81(24):1879–1886

    Article  CAS  PubMed  Google Scholar 

  48. Hoskins KF, Zwaagstra A, Ranz M (2006) Validation of a tool for identifying women at high risk for hereditary breast cancer in population-based screening. Cancer 107(8):1769–1776

    Article  PubMed  Google Scholar 

  49. Greene MH, Piedmonte M, Alberts D, Gail M, Hensley M, Miner Z, Mai PL, Loud J, Rodriguez G, Basil J, Boggess J, Schwartz PE, Kelley JL, Wakeley KE, Minasian L, Skates S (2008) A prospective study of risk-reducing salpingo-oophorectomy and longitudinal CA-125 screening among women at increased genetic risk of ovarian cancer: design and baseline characteristics: a Gynecologic Oncology Group study. Cancer Epidemiol Biomarkers Prev 17(3):594–604

    Article  PubMed  Google Scholar 

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Acknowledgments

The Breast Imaging Study (NCI Protocol #01-C-009); The Susceptibility to Breast Cancer Study (NCI Protocol #00-C-0079/NNMC Protocol #NNMC.2000.0010). We wish to thank Ruthann Giusti, Christine Mueller, and Paul Han for clinical support; Nicole Dupree, Jason Hu, Beth Mittl, Usha Singh, and Andrea Wilson for their help in data preparation; Pamela Klein for the original design of the NCI/NNMC Susceptibility to Breast Cancer Study; and Fang Fang Wu for the Cumulus density assessments. Special thanks to all our study participants, without whose cooperation this study could not have been done. Financial Support: This project was supported by the Intramural Research Program of the National Cancer Institute, and by contracts NO2-CP-11019-50 and NO2-CP-65504-50 with Westat, Inc. Dr. Gierach was supported by the NCI Cancer Prevention Fellowship Program. The views expressed in this article are those of the author and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, nor the U.S. Government.

Author information

Author notes

  1. Catherine K. Chow

    Present address: Washington Radiology Associates, Fairfax, VA, 22031, USA

  2. Claudia Giambartolomei

    Present address: Cambridge University, Cambridge, CB2 1TN, UK

Authors and Affiliations

  1. Hormonal and Reproductive Epidemiology Branch, Division of Cancer Epidemiology and Genetics and Cancer Prevention Fellowship Program, Office of Preventive Oncology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Gretchen L. Gierach

  2. Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Jennifer T. Loud, Claudia Giambartolomei, Phuong L. Mai & Mark H. Greene

  3. Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Mitchell H. Gail

  4. Diagnostic Radiology Department, National Institutes of Health Clinical Center, Bethesda, MD, USA

    Catherine K. Chow

  5. Coordinating Center for Clinical Trials, Office of the Director, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Sheila A. Prindiville

  6. Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA

    Jennifer Eng-Wong

  7. Uniformed Services University of the Health Sciences, Bethesda, MD, USA

    Peter W. Soballe

  8. Department of Radiological Sciences, Uniformed Services University of the Health Sciences, Bethesda, MD, USA

    Claudia E. Galbo

  9. Westat Corporation, Rockville, MD, USA

    Kathryn Nichols

  10. Genetics Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA

    Kathleen A. Calzone

  11. Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, MN, USA

    Celine Vachon

  12. 6120 Executive Blvd., Suite 550, Room 5016, Rockville, MD, 20892, USA

    Gretchen L. Gierach

  13. 6120 Executive Blvd., Room 7028, Rockville, MD, 20892, USA

    Jennifer T. Loud

  14. 6120 Executive Blvd., Suite 300, Rockville, MD, 20892, USA

    Sheila A. Prindiville

  15. 3800 Reservoir Rd. NW, Washington, DC, 20007, USA

    Jennifer Eng-Wong

  16. 34730 Bob Wilson Dr., Suite 400, San Diego, CA, 92134, USA

    Peter W. Soballe

  17. 6120 Executive Blvd., Room 7022, Rockville, MD, 20892, USA

    Phuong L. Mai

  18. National Naval Medical Center, Bethesda, MD, 20814, USA

    Claudia E. Galbo

  19. 6110 Executive Blvd., Suite 400, Rockville, MD, 20852, USA

    Kathryn Nichols

  20. 8901 Wisconsin Ave., Building 8, Room 5101, Bethesda, MD, 20889, USA

    Kathleen A. Calzone

  21. Charlton 6-239, 200 First Street Southwest, Rochester, MN, 55905, USA

    Celine Vachon

  22. 6120 Executive Blvd., Room 8032, Rockville, MD, 20892, USA

    Mitchell H. Gail

  23. 6120 Executive Blvd., Room 7032, Rockville, MD, 20892, USA

    Mark H. Greene

Authors
  1. Gretchen L. Gierach
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  2. Jennifer T. Loud
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  3. Catherine K. Chow
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  4. Sheila A. Prindiville
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  5. Jennifer Eng-Wong
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  7. Claudia Giambartolomei
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  8. Phuong L. Mai
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  9. Claudia E. Galbo
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  10. Kathryn Nichols
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  11. Kathleen A. Calzone
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  12. Celine Vachon
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  13. Mitchell H. Gail
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  14. Mark H. Greene
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Corresponding author

Correspondence to Gretchen L. Gierach.

Additional information

C. K. Chow was previously with the Diagnostic Radiology Department, Warren G. Magnuson Clinical Center, NIH, Bethesda, MD.

C. Giambartolomei was previously with the Clinical Genetics Branch, NCI, Bethesda, MD.

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Gierach, G.L., Loud, J.T., Chow, C.K. et al. 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, 245–255 (2010). https://doi.org/10.1007/s10549-010-0749-7

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