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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

Breast Cancer Research and Treatment volume 123, pages 245–255 (2010)Cite this article

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

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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

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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  6. Peter W. Soballe
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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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Keywords

  • Mammographic density
  • Breast cancer risk
  • Breast cancer screening
  • Gene, BRCA1
  • Gene, BRCA2
  • Genetic predisposition to disease