Skip to main content
Top
Published in: Breast Cancer Research 5/2014

Open Access 01-10-2014 | Research article

Digital mammographic density and breast cancer risk: a case–control study of six alternative density assessment methods

Authors: Amanda Eng, Zoe Gallant, John Shepherd, Valerie McCormack, Jingmei Li, Mitch Dowsett, Sarah Vinnicombe, Steve Allen, Isabel dos-Santos-Silva

Published in: Breast Cancer Research | Issue 5/2014

Login to get access

Abstract

Introduction

Mammographic density is a strong breast cancer risk factor and a major determinant of screening sensitivity. However, there is currently no validated estimation method for full-field digital mammography (FFDM).

Methods

The performance of three area-based approaches (BI-RADS, the semi-automated Cumulus, and the fully-automated ImageJ-based approach) and three fully-automated volumetric methods (Volpara, Quantra and single energy x-ray absorptiometry (SXA)) were assessed in 3168 FFDM images from 414 cases and 685 controls. Linear regression models were used to assess associations between breast cancer risk factors and density among controls, and logistic regression models to assess density-breast cancer risk associations, adjusting for age, body mass index (BMI) and reproductive variables.

Results

Quantra and the ImageJ-based approach failed to produce readings for 4% and 11% of the participants. All six density assessment methods showed that percent density (PD) was inversely associated with age, BMI, being parous and postmenopausal at mammography. PD was positively associated with breast cancer for all methods, but with the increase in risk per standard deviation increment in PD being highest for Volpara (1.83; 95% CI: 1.51 to 2.21) and Cumulus (1.58; 1.33 to 1.88) and lower for the ImageJ-based method (1.45; 1.21 to 1.74), Quantra (1.40; 1.19 to 1.66) and SXA (1.37; 1.16 to 1.63). Women in the top PD quintile (or BI-RADS 4) had 8.26 (4.28 to 15.96), 3.94 (2.26 to 6.86), 3.38 (2.00 to 5.72), 2.99 (1.76 to 5.09), 2.55 (1.46 to 4.43) and 2.96 (0.50 to 17.5) times the risk of those in the bottom one (or BI-RADS 1), respectively, for Volpara, Quantra, Cumulus, SXA, ImageJ-based method, and BI-RADS (P for trend <0.0001 for all). The ImageJ-based method had a slightly higher ability to discriminate between cases and controls (area under the curve (AUC) for PD = 0.68, P = 0.05), and Quantra slightly lower (AUC = 0.63; P = 0.06), than Cumulus (AUC = 0.65).

Conclusions

Fully-automated methods are valid alternatives to the labour-intensive "gold standard" Cumulus for quantifying density in FFDM. The choice of a particular method will depend on the aims and setting but the same approach will be required for longitudinal density assessments.
Appendix
Available only for authorised users
Literature
1.
go back to reference Boyd NF, Rommens JM, Vogt K, Lee V, Hopper JL, Yaffe MJ, Paterson AD: Mammographic breast density as an intermediate phenotype for breast cancer. Lancet Oncol. 2005, 6: 798-808. 10.1016/S1470-2045(05)70390-9.CrossRefPubMed Boyd NF, Rommens JM, Vogt K, Lee V, Hopper JL, Yaffe MJ, Paterson AD: Mammographic breast density as an intermediate phenotype for breast cancer. Lancet Oncol. 2005, 6: 798-808. 10.1016/S1470-2045(05)70390-9.CrossRefPubMed
2.
go back to reference McCormack VA, dos Santos SI: Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev. 2006, 15: 1159-1169. 10.1158/1055-9965.EPI-06-0034.CrossRefPubMed McCormack VA, dos Santos SI: Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev. 2006, 15: 1159-1169. 10.1158/1055-9965.EPI-06-0034.CrossRefPubMed
3.
go back to reference Boyd NF, Guo H, Martin LJ, Sun L, Stone J, Fishell E, Jong RA, Hislop G, Chiarelli A, Minkin S, Yaffe MJ: Mammographic density and the risk and detection of breast cancer. N Engl J Med. 2007, 356: 227-236. 10.1056/NEJMoa062790.CrossRefPubMed Boyd NF, Guo H, Martin LJ, Sun L, Stone J, Fishell E, Jong RA, Hislop G, Chiarelli A, Minkin S, Yaffe MJ: Mammographic density and the risk and detection of breast cancer. N Engl J Med. 2007, 356: 227-236. 10.1056/NEJMoa062790.CrossRefPubMed
4.
go back to reference Mandelson MT, Oestreicher N, Porter PL, White D, Finder CA, Taplin SH, White E: Breast density as a predictor of mammographic detection: comparison of interval- and screen-detected cancers. J Natl Cancer Inst. 2000, 92: 1081-1087. 10.1093/jnci/92.13.1081.CrossRefPubMed Mandelson MT, Oestreicher N, Porter PL, White D, Finder CA, Taplin SH, White E: Breast density as a predictor of mammographic detection: comparison of interval- and screen-detected cancers. J Natl Cancer Inst. 2000, 92: 1081-1087. 10.1093/jnci/92.13.1081.CrossRefPubMed
5.
go back to reference BI-RADS Mammography Breast Imaging Atlas. 2003, American College of Radiology, Reston, Va BI-RADS Mammography Breast Imaging Atlas. 2003, American College of Radiology, Reston, Va
6.
go back to reference Byng JW, Boyd NF, Fishell E, Jong RA, Yaffe MJ: The quantitative analysis of mammographic densities. Phys Med Biol. 1994, 39: 1629-1638. 10.1088/0031-9155/39/10/008.CrossRefPubMed Byng JW, Boyd NF, Fishell E, Jong RA, Yaffe MJ: The quantitative analysis of mammographic densities. Phys Med Biol. 1994, 39: 1629-1638. 10.1088/0031-9155/39/10/008.CrossRefPubMed
7.
go back to reference Boyd NF, Byng JW, Jong RA, Fishell EK, Little LE, Miller AB, Lockwood GA, Tritchler DL, Yaffe MJ: Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian National Breast Screening Study. J Natl Cancer Inst. 1995, 87: 670-675. 10.1093/jnci/87.9.670.CrossRefPubMed Boyd NF, Byng JW, Jong RA, Fishell EK, Little LE, Miller AB, Lockwood GA, Tritchler DL, Yaffe MJ: Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian National Breast Screening Study. J Natl Cancer Inst. 1995, 87: 670-675. 10.1093/jnci/87.9.670.CrossRefPubMed
8.
go back to reference Li J, Szekely L, Eriksson L, Heddson B, Sundbom A, Czene K, Hall P, Humphreys K: High-throughput mammographic-density measurement: a tool for risk prediction of breast cancer. Breast Cancer Res. 2012, 14: R114-10.1186/bcr3238.CrossRefPubMedPubMedCentral Li J, Szekely L, Eriksson L, Heddson B, Sundbom A, Czene K, Hall P, Humphreys K: High-throughput mammographic-density measurement: a tool for risk prediction of breast cancer. Breast Cancer Res. 2012, 14: R114-10.1186/bcr3238.CrossRefPubMedPubMedCentral
9.
go back to reference Heine JJ, Scott CG, Sellers TA, Brandt KR, Serie DJ, Wu FF, Morton MJ, Schueler BA, Couch FJ, Olson JE, Pankratz VS, Vachon CM: A novel automated mammographic density measure and breast cancer risk. J Natl Cancer Inst. 2012, 104: 1028-1037. 10.1093/jnci/djs254.CrossRefPubMedPubMedCentral Heine JJ, Scott CG, Sellers TA, Brandt KR, Serie DJ, Wu FF, Morton MJ, Schueler BA, Couch FJ, Olson JE, Pankratz VS, Vachon CM: A novel automated mammographic density measure and breast cancer risk. J Natl Cancer Inst. 2012, 104: 1028-1037. 10.1093/jnci/djs254.CrossRefPubMedPubMedCentral
10.
go back to reference Kallenberg MG, Lokate M, van Gils CH, Karssemeijer N: Automatic breast density segmentation: an integration of different approaches. Phys Med Biol. 2011, 56: 2715-2729. 10.1088/0031-9155/56/9/005.CrossRefPubMed Kallenberg MG, Lokate M, van Gils CH, Karssemeijer N: Automatic breast density segmentation: an integration of different approaches. Phys Med Biol. 2011, 56: 2715-2729. 10.1088/0031-9155/56/9/005.CrossRefPubMed
11.
go back to reference Aitken Z, McCormack VA, Highnam RP, Martin L, Gunasekara A, Melnichouk O, Mawdsley G, Peressotti C, Yaffe M, Boyd NF, Dos Santos Silva I: Screen-film mammographic density and breast cancer risk: a comparison of the volumetric standard mammogram form and the interactive threshold measurement methods. Cancer Epidemiol Biomarkers Prev. 2010, 19: 418-428. 10.1158/1055-9965.EPI-09-1059.CrossRefPubMedPubMedCentral Aitken Z, McCormack VA, Highnam RP, Martin L, Gunasekara A, Melnichouk O, Mawdsley G, Peressotti C, Yaffe M, Boyd NF, Dos Santos Silva I: Screen-film mammographic density and breast cancer risk: a comparison of the volumetric standard mammogram form and the interactive threshold measurement methods. Cancer Epidemiol Biomarkers Prev. 2010, 19: 418-428. 10.1158/1055-9965.EPI-09-1059.CrossRefPubMedPubMedCentral
12.
go back to reference Shepherd JA, Kerlikowske K, Ma L, Duewer F, Fan B, Wang J, Malkov S, Vittinghoff E, Cummings SR: Volume of mammographic density and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2011, 20: 1473-1482. 10.1158/1055-9965.EPI-10-1150.CrossRefPubMedPubMedCentral Shepherd JA, Kerlikowske K, Ma L, Duewer F, Fan B, Wang J, Malkov S, Vittinghoff E, Cummings SR: Volume of mammographic density and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2011, 20: 1473-1482. 10.1158/1055-9965.EPI-10-1150.CrossRefPubMedPubMedCentral
13.
go back to reference Pawluczyk O, Augustine BJ, Yaffe MJ, Rico D, Yang J, Mawdsley GE, Boyd NF: A volumetric method for estimation of breast density on digitized screen-film mammograms. Med Phys. 2003, 30: 352-364. 10.1118/1.1539038.CrossRefPubMed Pawluczyk O, Augustine BJ, Yaffe MJ, Rico D, Yang J, Mawdsley GE, Boyd NF: A volumetric method for estimation of breast density on digitized screen-film mammograms. Med Phys. 2003, 30: 352-364. 10.1118/1.1539038.CrossRefPubMed
14.
go back to reference Boyd N, Martin L, Gunasekara A, Melnichouk O, Maudsley G, Peressotti C, Yaffe M, Minkin S: Mammographic density and breast cancer risk: evaluation of a novel method of measuring breast tissue volumes. Cancer Epidemiol Biomarkers Prev. 2009, 18: 1754-1762. 10.1158/1055-9965.EPI-09-0107.CrossRefPubMed Boyd N, Martin L, Gunasekara A, Melnichouk O, Maudsley G, Peressotti C, Yaffe M, Minkin S: Mammographic density and breast cancer risk: evaluation of a novel method of measuring breast tissue volumes. Cancer Epidemiol Biomarkers Prev. 2009, 18: 1754-1762. 10.1158/1055-9965.EPI-09-0107.CrossRefPubMed
15.
go back to reference van Engeland S, Snoeren PR, Huisman H, Boetes C, Karssemeijer N: Volumetric breast density estimation from full-field digital mammograms. IEEE Trans Med Imaging. 2006, 25: 273-282. 10.1109/TMI.2005.862741.CrossRefPubMed van Engeland S, Snoeren PR, Huisman H, Boetes C, Karssemeijer N: Volumetric breast density estimation from full-field digital mammograms. IEEE Trans Med Imaging. 2006, 25: 273-282. 10.1109/TMI.2005.862741.CrossRefPubMed
16.
go back to reference Lokate M, Kallenberg MG, Karssemeijer N, Van den Bosch MA, Peeters PH, Van Gils CH: Volumetric breast density from full-field digital mammograms and its association with breast cancer risk factors: a comparison with a threshold method. Cancer Epidemiol Biomarkers Prev. 2010, 19: 3096-3105. 10.1158/1055-9965.EPI-10-0703.CrossRefPubMed Lokate M, Kallenberg MG, Karssemeijer N, Van den Bosch MA, Peeters PH, Van Gils CH: Volumetric breast density from full-field digital mammograms and its association with breast cancer risk factors: a comparison with a threshold method. Cancer Epidemiol Biomarkers Prev. 2010, 19: 3096-3105. 10.1158/1055-9965.EPI-10-0703.CrossRefPubMed
17.
go back to reference Ciatto S, Bernardi D, Calabrese M, Durando M, Gentilini MA, Mariscotti G, Monetti F, Moriconi E, Pesce B, Roselli A, Stevanin C, Tapparelli M, Houssami N: A first evaluation of breast radiological density assessment by QUANTRA software as compared to visual classification. Breast. 2012, 21: 503-506. 10.1016/j.breast.2012.01.005.CrossRefPubMed Ciatto S, Bernardi D, Calabrese M, Durando M, Gentilini MA, Mariscotti G, Monetti F, Moriconi E, Pesce B, Roselli A, Stevanin C, Tapparelli M, Houssami N: A first evaluation of breast radiological density assessment by QUANTRA software as compared to visual classification. Breast. 2012, 21: 503-506. 10.1016/j.breast.2012.01.005.CrossRefPubMed
18.
go back to reference Jeffreys MHJ, Highnam R, Davey Smith G: Comparing a New Volumetric Breast Density Method (Volpara TM) to Cumulus. International Workshop on Digital Mammography 2010. 2010, Springer Berlin Heidelberg, Girona, Spain Jeffreys MHJ, Highnam R, Davey Smith G: Comparing a New Volumetric Breast Density Method (Volpara TM) to Cumulus. International Workshop on Digital Mammography 2010. 2010, Springer Berlin Heidelberg, Girona, Spain
19.
go back to reference Vinnicombe S, Pinto Pereira SM, McCormack VA, Shiel S, Perry N, dos Santos SI: Full-field digital versus screen-film mammography: comparison within the UK breast screening program and systematic review of published data. Radiology. 2009, 251: 347-358. 10.1148/radiol.2512081235.CrossRefPubMed Vinnicombe S, Pinto Pereira SM, McCormack VA, Shiel S, Perry N, dos Santos SI: Full-field digital versus screen-film mammography: comparison within the UK breast screening program and systematic review of published data. Radiology. 2009, 251: 347-358. 10.1148/radiol.2512081235.CrossRefPubMed
20.
go back to reference Sovio U, Li J, Aitken Z, Humphreys K, Czene K, Moss S, Hall P, McCormack V, dos-Santos-Silva I: Comparison of fully and semi-automated area-based methods for measuring mammographic density and predicting breast cancer risk. Br J Cancer. 2014, 110: 1908-1916. 10.1038/bjc.2014.82.CrossRefPubMedPubMedCentral Sovio U, Li J, Aitken Z, Humphreys K, Czene K, Moss S, Hall P, McCormack V, dos-Santos-Silva I: Comparison of fully and semi-automated area-based methods for measuring mammographic density and predicting breast cancer risk. Br J Cancer. 2014, 110: 1908-1916. 10.1038/bjc.2014.82.CrossRefPubMedPubMedCentral
21.
go back to reference Stata Statistical Software: Release 13. 2013, StataCorp LP, College Station, TX Stata Statistical Software: Release 13. 2013, StataCorp LP, College Station, TX
22.
go back to reference McCormack VA, Perry NM, Vinnicombe SJ, Dos Santos Silva I: Changes and tracking of mammographic density in relation to Pike's model of breast tissue ageing: a UK longitudinal study. Int J Cancer. 2009, 127: 452-461. McCormack VA, Perry NM, Vinnicombe SJ, Dos Santos Silva I: Changes and tracking of mammographic density in relation to Pike's model of breast tissue ageing: a UK longitudinal study. Int J Cancer. 2009, 127: 452-461.
23.
go back to reference McCormack VA, Highnam R, Perry N, dos Santos SI: Comparison of a new and existing method of mammographic density measurement: intramethod reliability and associations with known risk factors. Cancer Epidemiol Biomarkers Prev. 2007, 16: 1148-1154. 10.1158/1055-9965.EPI-07-0085.CrossRefPubMedPubMedCentral McCormack VA, Highnam R, Perry N, dos Santos SI: Comparison of a new and existing method of mammographic density measurement: intramethod reliability and associations with known risk factors. Cancer Epidemiol Biomarkers Prev. 2007, 16: 1148-1154. 10.1158/1055-9965.EPI-07-0085.CrossRefPubMedPubMedCentral
24.
go back to reference Pinto Pereira SM, McCormack VA, Hipwell JH, Record C, Wilkinson LS, Moss SM, Hawkes DJ, Dos Santos SI: Localized fibroglandular tissue as a predictor of future tumour location within the breast. Cancer Epidemiol Biomarkers Prev. 2011, 20: 1718-1725. 10.1158/1055-9965.EPI-11-0423.CrossRefPubMed Pinto Pereira SM, McCormack VA, Hipwell JH, Record C, Wilkinson LS, Moss SM, Hawkes DJ, Dos Santos SI: Localized fibroglandular tissue as a predictor of future tumour location within the breast. Cancer Epidemiol Biomarkers Prev. 2011, 20: 1718-1725. 10.1158/1055-9965.EPI-11-0423.CrossRefPubMed
25.
go back to reference Vachon CM, van Gils CH, Sellers TA, Ghosh K, Pruthi S, Brandt KR, Pankratz VS: Mammographic density, breast cancer risk and risk prediction. Breast Cancer Res. 2007, 9: 217-10.1186/bcr1829.CrossRefPubMedPubMedCentral Vachon CM, van Gils CH, Sellers TA, Ghosh K, Pruthi S, Brandt KR, Pankratz VS: Mammographic density, breast cancer risk and risk prediction. Breast Cancer Res. 2007, 9: 217-10.1186/bcr1829.CrossRefPubMedPubMedCentral
26.
go back to reference Darabi H, Czene K, Zhao W, Liu J, Hall P, Humphreys K: Breast cancer risk prediction and individualised screening based on common genetic variation and breast density measurement. Breast Cancer Res. 2012, 14: R25-10.1186/bcr3110.CrossRefPubMedPubMedCentral Darabi H, Czene K, Zhao W, Liu J, Hall P, Humphreys K: Breast cancer risk prediction and individualised screening based on common genetic variation and breast density measurement. Breast Cancer Res. 2012, 14: R25-10.1186/bcr3110.CrossRefPubMedPubMedCentral
27.
go back to reference Cuzick J, Warwick J, Pinney E, Warren RM, Duffy SW: Tamoxifen and breast density in women at increased risk of breast cancer. J Natl Cancer Inst. 2004, 96: 621-628. 10.1093/jnci/djh106.CrossRefPubMed Cuzick J, Warwick J, Pinney E, Warren RM, Duffy SW: Tamoxifen and breast density in women at increased risk of breast cancer. J Natl Cancer Inst. 2004, 96: 621-628. 10.1093/jnci/djh106.CrossRefPubMed
28.
go back to reference Cuzick J, Warwick J, Pinney E, Duffy SW, Cawthorn S, Howell A, Forbes JF, Warren RM: Tamoxifen-induced reduction in mammographic density and breast cancer risk reduction: a nested case–control study. J Natl Cancer Inst. 2011, 103: 744-752. 10.1093/jnci/djr079.CrossRefPubMed Cuzick J, Warwick J, Pinney E, Duffy SW, Cawthorn S, Howell A, Forbes JF, Warren RM: Tamoxifen-induced reduction in mammographic density and breast cancer risk reduction: a nested case–control study. J Natl Cancer Inst. 2011, 103: 744-752. 10.1093/jnci/djr079.CrossRefPubMed
29.
go back to reference Howell A, Astley S, Warwick J, Stavrinos P, Sahin S, Ingham S, McBurney H, Eckersley B, Harvie M, Wilson M, Beetles U, Warren R, Hufton A, Sergeant J, Newman W, Buchan I, Cuzick J, Evans DG: Prevention of breast cancer in the context of a national breast screening programme. J Intern Med. 2012, 271: 321-330. 10.1111/j.1365-2796.2012.02525.x.CrossRefPubMed Howell A, Astley S, Warwick J, Stavrinos P, Sahin S, Ingham S, McBurney H, Eckersley B, Harvie M, Wilson M, Beetles U, Warren R, Hufton A, Sergeant J, Newman W, Buchan I, Cuzick J, Evans DG: Prevention of breast cancer in the context of a national breast screening programme. J Intern Med. 2012, 271: 321-330. 10.1111/j.1365-2796.2012.02525.x.CrossRefPubMed
30.
go back to reference Sandberg ME, Li J, Hall P, Hartman M, Dos-Santos-Silva I, Humphreys K, Czene K: Change of mammographic density predicts the risk of contralateral breast cancer - a case–control study. Breast Cancer Res. 2013, 15: R57-10.1186/bcr3451.CrossRefPubMedPubMedCentral Sandberg ME, Li J, Hall P, Hartman M, Dos-Santos-Silva I, Humphreys K, Czene K: Change of mammographic density predicts the risk of contralateral breast cancer - a case–control study. Breast Cancer Res. 2013, 15: R57-10.1186/bcr3451.CrossRefPubMedPubMedCentral
31.
go back to reference Nicholson BT, LoRusso AP, Smolkin M, Bovbjerg VE, Petroni GR, Harvey JA: Accuracy of assigned BI-RADS breast density category definitions. Acad Radiol. 2006, 13: 1143-1149. 10.1016/j.acra.2006.06.005.CrossRefPubMed Nicholson BT, LoRusso AP, Smolkin M, Bovbjerg VE, Petroni GR, Harvey JA: Accuracy of assigned BI-RADS breast density category definitions. Acad Radiol. 2006, 13: 1143-1149. 10.1016/j.acra.2006.06.005.CrossRefPubMed
32.
go back to reference Gao J, Warren R, Warren-Forward H, Forbes JF: Reproducibility of visual assessment on mammographic density. Breast Cancer Res Treat. 2008, 108: 121-127. 10.1007/s10549-007-9581-0.CrossRefPubMed Gao J, Warren R, Warren-Forward H, Forbes JF: Reproducibility of visual assessment on mammographic density. Breast Cancer Res Treat. 2008, 108: 121-127. 10.1007/s10549-007-9581-0.CrossRefPubMed
33.
go back to reference Lobbes MB, Cleutjens JP, Lima Passos V, Frotscher C, Lahaye MJ, Keymeulen KB, Beets-Tan RG, Wildberger J, Boetes C: Density is in the eye of the beholder: visual versus semi-automated assessment of breast density on standard mammograms. Insights Imaging. 2012, 3: 91-99. 10.1007/s13244-011-0139-7.CrossRefPubMed Lobbes MB, Cleutjens JP, Lima Passos V, Frotscher C, Lahaye MJ, Keymeulen KB, Beets-Tan RG, Wildberger J, Boetes C: Density is in the eye of the beholder: visual versus semi-automated assessment of breast density on standard mammograms. Insights Imaging. 2012, 3: 91-99. 10.1007/s13244-011-0139-7.CrossRefPubMed
Metadata
Title
Digital mammographic density and breast cancer risk: a case–control study of six alternative density assessment methods
Authors
Amanda Eng
Zoe Gallant
John Shepherd
Valerie McCormack
Jingmei Li
Mitch Dowsett
Sarah Vinnicombe
Steve Allen
Isabel dos-Santos-Silva
Publication date
01-10-2014
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 5/2014
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-014-0439-1

Other articles of this Issue 5/2014

Breast Cancer Research 5/2014 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine