© 1995 by Oxford University Press
Journal of the National Cancer Institute, Vol. 87, No. 21, 1622-1629,
November 1, 1995
© 1995 Oxford University Press
Mammographic Features and Breast Cancer Risk: Effects With Time, Age, and Menopause Status
Environmental Epidemiology Branch, Division of Cancer Etiology, National Cancer Institute Bethesda, MD
Department of Radiology, Hutzel Hospital Detroit, MI
Department of Epidemiology. University of California Los Angeles, School of Public Health
J. Wolfe (deceased September 1993), Department of Radiology, Hutzel Hospital
Correspondence to present address: Celia Byrne, Ph.D., Channing Laboratory, 180 Longwood Ave., Boston, MA 02115.
Background: Mammographic images from women with a high proportion of epithelial and stromal breast tissues are described as showing high-density parenchymal patterns. Most past studies that noted an increase in breast cancer risk associated with mammographic parenchymal patterns showing high density either 1) lacked information on other breast cancer risk factors, 2) were too small, or 3) included insufficient follow-up time to adequately resolve persisting doubts whether mammographic features are "independent" measures of breast cancer risk and not a detection artifact. Purpose: The purpose of this study was twofold: 1) to evaluate the associations between mammographic features and other breast cancer risk factors and 2) to assess effects of mammographic features on breast cancer risk by time, age, and menopause status. Methods: To address these questions, we analyzed detailed information from a large, nested case-control study with 16 years of follow-up. This study used information from both screening and follow-up phases of the Breast Cancer Detection Demonstration Project, a nationwide program that offered annual breast cancer screening for more than 280 000 women from 1973 to 1980. Mammographic features were assessed from the base-line screening mammographic examination for 1880 incident case subjects and 2152 control subjects. Control subjects were randomly selected from women of the same age and race as each case subject. Control subjects attended the same screening center as the case subject and were free of breast cancer at the case subject's date of diagnosis. Odds ratios (ORs) with 95% confidence intervals (CIs) provided estimates of the relative risk of breast cancer. Results: Mammographic features were associated with known breast cancer risk factors. However, the high-density parenchymal pattern effects were independent of family history, age at first birth, alcohol consumption, and benign breast disease. The increased risk for women with Wolfe's two high-density parenchymal patterns, P2 (OR = 3.2; 95% CI = 2.5–4.0) and Dy (OR = 2.9; 95% CI = 2.2–3.9), was explained primarily by measured percent of the breast with dense mammographic appearance. Compared with women with no visible breast density, women who had a breast density of 75% or greater had an almost fivefold increased risk of breast cancer (95% CI = 3.6–7.1). These effects persisted for 10 or more years and were noted for both premenopausal and postmenopausal women of all ages. Conclusions: Of the breast cancer risk factors assessed in the participants, high-density mammographic parenchymal patterns, as measured by the proportion of breast area composed of epithelial and stromal tissue, had the greatest impact on breast cancer risk. Of the breast cancers in this study, 28% were attributable to having 50% or greater breast density. [J Natl Cancer Inst 1995;87:1622–9]
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S. Berube, C. Diorio, B. Masse, N. Hebert-Croteau, C. Byrne, G. Cote, M. Pollak, M. Yaffe, and J. Brisson Vitamin D and Calcium Intakes from Food or Supplements and Mammographic Breast Density Cancer Epidemiol. Biomarkers Prev., July 1, 2005; 14(7): 1653 - 1659. [Abstract] [Full Text] [PDF]
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J. R. Cerhan, T. A. Sellers, C. A. Janney, V. S. Pankratz, K. R. Brandt, and C. M. Vachon Prenatal and Perinatal Correlates of Adult Mammographic Breast Density Cancer Epidemiol. Biomarkers Prev., June 1, 2005; 14(6): 1502 - 1508. [Abstract] [Full Text] [PDF]
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G. Torres-Mejia, B. De Stavola, D. S. Allen, J. J. Perez-Gavilan, J. M. Ferreira, I. S. Fentiman, and I. dos Santos Silva Mammographic Features and Subsequent Risk of Breast Cancer: A Comparison of Qualitative and Quantitative Evaluations in the Guernsey Prospective Studies Cancer Epidemiol. Biomarkers Prev., May 1, 2005; 14(5): 1052 - 1059. [Abstract] [Full Text] [PDF]
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K. Kerlikowske, J. Shepherd, J. Creasman, J. A. Tice, E. Ziv, and S. R. Cummings Are Breast Density and Bone Mineral Density Independent Risk Factors for Breast Cancer? J Natl Cancer Inst, March 2, 2005; 97(5): 368 - 374. [Abstract] [Full Text] [PDF]
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E. S. Schernhammer, J. M. Holly, M. N. Pollak, and S. E. Hankinson Circulating Levels of Insulin-like Growth Factors, their Binding Proteins, and Breast Cancer Risk Cancer Epidemiol. Biomarkers Prev., March 1, 2005; 14(3): 699 - 704. [Abstract] [Full Text] [PDF]
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E. Ziv, J. Tice, R. Smith-Bindman, J. Shepherd, S. Cummings, and K. Kerlikowske Mammographic Density and Estrogen Receptor Status of Breast Cancer Cancer Epidemiol. Biomarkers Prev., December 1, 2004; 13(12): 2090 - 2095. [Abstract] [Full Text] [PDF]
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D. Heng, F. Gao, R. Jong, E. Fishell, M. Yaffe, L. Martin, T. Li, J. Stone, L. Sun, J. Hopper, et al. Risk Factors for Breast Cancer Associated with Mammographic Features in Singaporean Chinese Women Cancer Epidemiol. Biomarkers Prev., November 1, 2004; 13(11): 1751 - 1758. [Abstract] [Full Text] [PDF]
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D. S. M. Buist, P. L. Porter, C. Lehman, S. H. Taplin, and E. White Factors Contributing to Mammography Failure in Women Aged 40-49 Years J Natl Cancer Inst, October 6, 2004; 96(19): 1432 - 1440. [Abstract] [Full Text] [PDF]
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L. A. Habel, J. J. Dignam, S. R. Land, M. Salane, A. M. Capra, and T. B. Julian Mammographic Density and Breast Cancer After Ductal Carcinoma In Situ J Natl Cancer Inst, October 6, 2004; 96(19): 1467 - 1472. [Abstract] [Full Text] [PDF]
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S. Berube, C. Diorio, W. Verhoek-Oftedahl, and J. Brisson Vitamin D, Calcium, and Mammographic Breast Densities Cancer Epidemiol. Biomarkers Prev., September 1, 2004; 13(9): 1466 - 1472. [Abstract] [Full Text] [PDF]
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G. Ursin, S. L. Palla, B. A. Reboussin, S. Slone, C. Wasilauskas, M. C. Pike, and G. A. Greendale Post-Treatment Change in Serum Estrone Predicts Mammographic Percent Density Changes in Women Who Received Combination Estrogen and Progestin in the Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial J. Clin. Oncol., July 15, 2004; 22(14): 2842 - 2848. [Abstract] [Full Text] [PDF]
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 R. G. Richards, D. M. Klotz, M. P. Walker, and R. P. DiAugustine Mammary Gland Branching Morphogenesis Is Diminished in Mice with a Deficiency of Insulin-like Growth Factor-I (IGF-I), But Not in Mice with a Liver-Specific Deletion of IGF-I Endocrinology, July 1, 2004; 145(7): 3106 - 3110. [Abstract] [Full Text] [PDF]
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 A. Decensi, B. Bonanni, L. Baglietto, A. Guerrieri-Gonzaga, F. Ramazzotto, H. Johansson, C. Robertson, I. Marinucci, F. Mariette, M. T. Sandri, et al. A Two-by-Two Factorial Trial Comparing Oral with Transdermal Estrogen Therapy and Fenretinide with Placebo on Breast Cancer Biomarkers Clin. Cancer Res., July 1, 2004; 10(13): 4389 - 4397. [Abstract] [Full Text] [PDF]
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P. M. Vacek and B. M. Geller A Prospective Study of Breast Cancer Risk Using Routine Mammographic Breast Density Measurements Cancer Epidemiol. Biomarkers Prev., May 1, 2004; 13(5): 715 - 722. [Abstract] [Full Text] [PDF]
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J. H. Lai, D. Vesprini, W. Zhang, M. J. Yaffe, M. Pollak, and S. A. Narod A Polymorphic Locus in the Promoter Region of the IGFBP3 Gene Is Related to Mammographic Breast Density Cancer Epidemiol. Biomarkers Prev., April 1, 2004; 13(4): 573 - 582. [Abstract] [Full Text] [PDF]
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E. O. Lillie, L. Bernstein, S. A. Ingles, W. J. Gauderman, G. E. Rivas, V. Gagalang, T. Krontiris, and G. Ursin Polymorphism in the Androgen Receptor and Mammographic Density in Women Taking and Not Taking Estrogen and Progestin Therapy Cancer Res., February 15, 2004; 64(4): 1237 - 1241. [Abstract] [Full Text] [PDF]
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Z. Chen, A. H. Wu, W. J. Gauderman, L. Bernstein, H. Ma, M. C. Pike, and G. Ursin Does Mammographic Density Reflect Ethnic Differences in Breast Cancer Incidence Rates? Am. J. Epidemiol., January 15, 2004; 159(2): 140 - 147. [Abstract] [Full Text] [PDF]
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S. B. Halls, P. Crystal, I. Karakis, S. Strano, and M. Koretz Statistical Comparison of Proportions Am. J. Roentgenol., January 1, 2004; 182 (1): 259 - 260. [Full Text] [PDF]
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J. A. Harvey and V. E. Bovbjerg Quantitative Assessment of Mammographic Breast Density: Relationship with Breast Cancer Risk Radiology, January 1, 2004; 230(1): 29 - 41. [Abstract] [Full Text] [PDF]
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M. A. Roubidoux, J. S. Kaur, K. A. Griffith, B. Stillwater, P. Novotny, and J. Sloan Relationship of Mammographic Parenchymal Patterns to Breast Cancer Risk Factors and Smoking in Alaska Native Women Cancer Epidemiol. Biomarkers Prev., October 1, 2003; 12(10): 1081 - 1086. [Abstract] [Full Text] [PDF]
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J. Brisson, C. Diorio, and B. Masse Wolfe's Parenchymal Pattern and Percentage of the Breast with Mammographic Densities: Redundant or Complementary Classifications? Cancer Epidemiol. Biomarkers Prev., August 1, 2003; 12(8): 728 - 732. [Abstract] [Full Text] [PDF]
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 D. Vranjesevic, C. Schiepers, D. H. Silverman, A. Quon, J. Villalpando, M. Dahlbom, M. E. Phelps, and J. Czernin Relationship Between 18F-FDG Uptake and Breast Density in Women with Normal Breast Tissue J. Nucl. Med., August 1, 2003; 44(8): 1238 - 1242. [Abstract] [Full Text] [PDF]
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J. Stone, A. Gunasekara, L. J. Martin, M. Yaffe, S. Minkin, and N. F. Boyd The Detection of Change in Mammographic Density Cancer Epidemiol. Biomarkers Prev., July 1, 2003; 12(7): 625 - 630. [Abstract] [Full Text] [PDF]
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M. A. Roubidoux, J. S. Kaur, K. A. Griffith, J. Sloan, C. Wilson, P. Novotny, and M. Lobell Correlates of Mammogram Density in Southwestern Native-American Women Cancer Epidemiol. Biomarkers Prev., June 1, 2003; 12(6): 552 - 558. [Abstract] [Full Text] [PDF]
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E. Ziv, J. Shepherd, R. Smith-Bindman, and K. Kerlikowske Mammographic Breast Density and Family History of Breast Cancer J Natl Cancer Inst, April 2, 2003; 95(7): 556 - 558. [Abstract] [Full Text] [PDF]
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G. Ursin, H. Ma, A. H. Wu, L. Bernstein, M. Salane, Y. R. Parisky, M. Astrahan, C. C. Siozon, and M. C. Pike Mammographic Density and Breast Cancer in Three Ethnic Groups Cancer Epidemiol. Biomarkers Prev., April 1, 2003; 12(4): 332 - 338. [Abstract] [Full Text] [PDF]
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 C. V. Clevenger, P. A. Furth, S. E. Hankinson, and L. A. Schuler The Role of Prolactin in Mammary Carcinoma Endocr. Rev., February 1, 2003; 24(1): 1 - 27. [Abstract] [Full Text] [PDF]
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R. T. Chlebowski and A. McTiernan Biological Significance of Interventions That Change Breast Density J Natl Cancer Inst, January 1, 2003; 95(1): 4 - 5. [Full Text] [PDF]
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G. A. Greendale, B. A. Reboussin, S. Slone, C. Wasilauskas, M. C. Pike, and G. Ursin Postmenopausal Hormone Therapy and Change in Mammographic Density J Natl Cancer Inst, January 1, 2003; 95(1): 30 - 37. [Abstract] [Full Text] [PDF]
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C. M. Vachon, T. A. Sellers, R. A. Vierkant, F.-F. Wu, and K. R. Brandt Case-Control Study of Increased Mammographic Breast Density Response to Hormone Replacement Therapy Cancer Epidemiol. Biomarkers Prev., November 1, 2002; 11(11): 1382 - 1388. [Abstract] [Full Text] [PDF]
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S. Prevrhal, J. A Shepherd, R. Smith-Bindman, S. R. Cummings, and K. Kerlikowske Accuracy of Mammographic Breast Density Analysis: Results of Formal Operator Training Cancer Epidemiol. Biomarkers Prev., November 1, 2002; 11(11): 1389 - 1393. [Abstract] [Full Text] [PDF]
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Z. Huo, M. L. Giger, O. I. Olopade, D. E. Wolverton, B. L. Weber, C. E. Metz, W. Zhong, and S. A. Cummings Computerized Analysis of Digitized Mammograms of BRCA1 and BRCA2 Gene Mutation Carriers Radiology, November 1, 2002; 225(2): 519 - 526. [Abstract] [Full Text] [PDF]
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