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Published in: Breast Cancer Research 6/2009

Open Access 01-12-2009 | Research article

Assessing the usefulness of a novel MRI-based breast density estimation algorithm in a cohort of women at high genetic risk of breast cancer: the UK MARIBS study

Authors: Deborah J Thompson, Martin O Leach, Gek Kwan-Lim, Simon A Gayther, Susan J Ramus, Iqbal Warsi, Fiona Lennard, Michael Khazen, Emilie Bryant, Sadie Reed, Caroline RM Boggis, D Gareth Evans, Rosalind A Eeles, Douglas F Easton, Ruth ML Warren, The UK study of MRI screening for breast cancer in women at high risk (MARIBS)

Published in: Breast Cancer Research | Issue 6/2009

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Abstract

Introduction

Mammographic breast density is one of the strongest known risk factors for breast cancer. We present a novel technique for estimating breast density based on 3D T1-weighted Magnetic Resonance Imaging (MRI) and evaluate its performance, including for breast cancer risk prediction, relative to two standard mammographic density-estimation methods.

Methods

The analyses were based on MRI (n = 655) and mammography (n = 607) images obtained in the course of the UK multicentre magnetic resonance imaging breast screening (MARIBS) study of asymptomatic women aged 31 to 49 years who were at high genetic risk of breast cancer. The MRI percent and absolute dense volumes were estimated using our novel algorithm (MRIBview) while mammographic percent and absolute dense area were estimated using the Cumulus thresholding algorithm and also using a 21-point Visual Assessment scale for one medio-lateral oblique image per woman. We assessed the relationships of the MRI and mammographic measures to one another, to standard anthropometric and hormonal factors, to BRCA1/2 genetic status, and to breast cancer risk (60 cases) using linear and Poisson regression.

Results

MRI percent dense volume is well correlated with mammographic percent dense area (R = 0.76) but overall gives estimates 8.1 percentage points lower (P < 0.0001). Both show strong associations with established anthropometric and hormonal factors. Mammographic percent dense area, and to a lesser extent MRI percent dense volume were lower in BRCA1 carriers (P = 0.001, P = 0.010 respectively) but there was no association with BRCA2 carrier status. The study was underpowered to detect expected associations between percent density and breast cancer, but women with absolute MRI dense volume in the upper half of the distribution had double the risk of those in the lower half (P = 0.009).

Conclusions

The MRIBview estimates of volumetric breast density are highly correlated with mammographic dense area but are not equivalent measures; the MRI absolute dense volume shows potential as a predictor of breast cancer risk that merits further investigation.
Appendix
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Literature
1.
go back to reference McCormack VA, dos Santos Silva I: 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 Silva I: 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
2.
go back to reference 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, Eeles R, Easton DF: Mammographic density and breast cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer Res. 2006, 66: 1866-1872. 10.1158/0008-5472.CAN-05-3368.CrossRefPubMed 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, Eeles R, Easton DF: Mammographic density and breast cancer risk in BRCA1 and BRCA2 mutation carriers. Cancer Res. 2006, 66: 1866-1872. 10.1158/0008-5472.CAN-05-3368.CrossRefPubMed
3.
go back to reference Khazen M, Warren RM, Boggis CR, Bryant EC, Reed S, Warsi I, Pointon LJ, Kwan-Lim GE, Thompson D, Eeles R, Easton D, Evans DG, Leach MO: A pilot study of compositional analysis of the breast and estimation of breast mammographic density using three-dimensional T1-weighted magnetic resonance imaging. Cancer Epidemiol Biomarkers Prev. 2008, 17: 2268-2274. 10.1158/1055-9965.EPI-07-2547.CrossRefPubMedPubMedCentral Khazen M, Warren RM, Boggis CR, Bryant EC, Reed S, Warsi I, Pointon LJ, Kwan-Lim GE, Thompson D, Eeles R, Easton D, Evans DG, Leach MO: A pilot study of compositional analysis of the breast and estimation of breast mammographic density using three-dimensional T1-weighted magnetic resonance imaging. Cancer Epidemiol Biomarkers Prev. 2008, 17: 2268-2274. 10.1158/1055-9965.EPI-07-2547.CrossRefPubMedPubMedCentral
4.
go back to reference Brown J, Buckley D, Coulthard A, Dixon AK, Dixon JM, Easton DF, Eeles RA, Evans DG, Gilbert FG, Graves M, Hayes C, Jenkins JP, Jones AP, Keevil SF, Leach MO, Liney GP, Moss SM, Padhani AR, Parker GJ, Pointon LJ, Ponder BA, Redpath TW, Sloane JP, Turnbull LW, Walker LG, Warren RM: Magnetic resonance imaging screening in women at genetic risk of breast cancer: imaging and analysis protocol for the UK multicentre study. UK MRI Breast Screening Study Advisory Group. Magn Reson Imaging. 2000, 18: 765-776. 10.1016/S0730-725X(00)00167-3.CrossRefPubMed Brown J, Buckley D, Coulthard A, Dixon AK, Dixon JM, Easton DF, Eeles RA, Evans DG, Gilbert FG, Graves M, Hayes C, Jenkins JP, Jones AP, Keevil SF, Leach MO, Liney GP, Moss SM, Padhani AR, Parker GJ, Pointon LJ, Ponder BA, Redpath TW, Sloane JP, Turnbull LW, Walker LG, Warren RM: Magnetic resonance imaging screening in women at genetic risk of breast cancer: imaging and analysis protocol for the UK multicentre study. UK MRI Breast Screening Study Advisory Group. Magn Reson Imaging. 2000, 18: 765-776. 10.1016/S0730-725X(00)00167-3.CrossRefPubMed
5.
go back to reference Leach MO, Boggis CR, Dixon AK, Easton DF, Eeles RA, Evans DG, Gilbert FJ, Griebsch I, Hoff RJ, Kessar P, Lakhani SR, Moss SM, Nerurkar A, Padhani AR, Pointon LJ, Thompson D, Warren RM: Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS). Lancet. 2005, 365: 1769-1778. 10.1016/S0140-6736(05)66646-9.CrossRefPubMed Leach MO, Boggis CR, Dixon AK, Easton DF, Eeles RA, Evans DG, Gilbert FJ, Griebsch I, Hoff RJ, Kessar P, Lakhani SR, Moss SM, Nerurkar A, Padhani AR, Pointon LJ, Thompson D, Warren RM: Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS). Lancet. 2005, 365: 1769-1778. 10.1016/S0140-6736(05)66646-9.CrossRefPubMed
6.
go back to reference Byng JW, Yaffe MJ, Lockwood GA, Little LE, Tritchler DL, Boyd NF: Automated analysis of mammographic densities and breast carcinoma risk. Cancer. 1997, 80: 66-74. 10.1002/(SICI)1097-0142(19970701)80:1<66::AID-CNCR9>3.0.CO;2-D.CrossRefPubMed Byng JW, Yaffe MJ, Lockwood GA, Little LE, Tritchler DL, Boyd NF: Automated analysis of mammographic densities and breast carcinoma risk. Cancer. 1997, 80: 66-74. 10.1002/(SICI)1097-0142(19970701)80:1<66::AID-CNCR9>3.0.CO;2-D.CrossRefPubMed
7.
go back to reference Soegaard M, Kjaer SK, Cox M, Wozniak E, Hogdall E, Hogdall C, Blaakaer J, Jacobs IJ, Gayther SA, Ramus SJ: BRCA1 and BRCA2 mutation prevalence and clinical characteristics of a population-based series of ovarian cancer cases from Denmark. Clin Cancer Res. 2008, 14: 3761-3767. 10.1158/1078-0432.CCR-07-4806.CrossRefPubMed Soegaard M, Kjaer SK, Cox M, Wozniak E, Hogdall E, Hogdall C, Blaakaer J, Jacobs IJ, Gayther SA, Ramus SJ: BRCA1 and BRCA2 mutation prevalence and clinical characteristics of a population-based series of ovarian cancer cases from Denmark. Clin Cancer Res. 2008, 14: 3761-3767. 10.1158/1078-0432.CCR-07-4806.CrossRefPubMed
9.
go back to reference Antoniou AC, Cunningham AP, Peto J, Evans DG, Lalloo F, Narod SA, Risch HA, Eyfjord JE, Hopper JL, Southey MC, Olsson H, Johannsson O, Borg A, Pasini B, Radice P, Manoukian S, Eccles DM, Tang N, Olah E, Anton-Culver H, Warner E, Lubinski J, Gronwald J, Gorski B, Tryggvadottir L, Syrjakoski K, Kallioniemi OP, Eerola H, Nevanlinna H, Pharoah PD, et al: The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions. Br J Cancer. 2008, 98: 1457-1466. 10.1038/sj.bjc.6604305.CrossRefPubMedPubMedCentral Antoniou AC, Cunningham AP, Peto J, Evans DG, Lalloo F, Narod SA, Risch HA, Eyfjord JE, Hopper JL, Southey MC, Olsson H, Johannsson O, Borg A, Pasini B, Radice P, Manoukian S, Eccles DM, Tang N, Olah E, Anton-Culver H, Warner E, Lubinski J, Gronwald J, Gorski B, Tryggvadottir L, Syrjakoski K, Kallioniemi OP, Eerola H, Nevanlinna H, Pharoah PD, et al: The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions. Br J Cancer. 2008, 98: 1457-1466. 10.1038/sj.bjc.6604305.CrossRefPubMedPubMedCentral
10.
go back to reference Eng-Wong J, Orzano-Birgani J, Chow CK, Venzon D, Yao J, Galbo CE, Zujewski JA, Prindiville S: Effect of raloxifene on mammographic density and breast magnetic resonance imaging in premenopausal women at increased risk for breast cancer. Cancer Epidemiol Biomarkers Prev. 2008, 17: 1696-1701. 10.1158/1055-9965.EPI-07-2752.CrossRefPubMedPubMedCentral Eng-Wong J, Orzano-Birgani J, Chow CK, Venzon D, Yao J, Galbo CE, Zujewski JA, Prindiville S: Effect of raloxifene on mammographic density and breast magnetic resonance imaging in premenopausal women at increased risk for breast cancer. Cancer Epidemiol Biomarkers Prev. 2008, 17: 1696-1701. 10.1158/1055-9965.EPI-07-2752.CrossRefPubMedPubMedCentral
11.
go back to reference Lee NA, Rusinek H, Weinreb J, Chandra R, Toth H, Singer C, Newstead G: Fatty and fibroglandular tissue volumes in the breasts of women 20-83 years old: comparison of X-ray mammography and computer-assisted MR imaging. AJR Am J Roentgenol. 1997, 168: 501-506.CrossRefPubMed Lee NA, Rusinek H, Weinreb J, Chandra R, Toth H, Singer C, Newstead G: Fatty and fibroglandular tissue volumes in the breasts of women 20-83 years old: comparison of X-ray mammography and computer-assisted MR imaging. AJR Am J Roentgenol. 1997, 168: 501-506.CrossRefPubMed
12.
go back to reference Wei J, Chan HP, Helvie MA, Roubidoux MA, Sahiner B, Hadjiiski LM, Zhou C, Paquerault S, Chenevert T, Goodsitt MM: Correlation between mammographic density and volumetric fibroglandular tissue estimated on breast MR images. Med Phys. 2004, 31: 933-942. 10.1118/1.1668512.CrossRefPubMed Wei J, Chan HP, Helvie MA, Roubidoux MA, Sahiner B, Hadjiiski LM, Zhou C, Paquerault S, Chenevert T, Goodsitt MM: Correlation between mammographic density and volumetric fibroglandular tissue estimated on breast MR images. Med Phys. 2004, 31: 933-942. 10.1118/1.1668512.CrossRefPubMed
13.
go back to reference Boyd N, Martin L, Stone J, Little L, Minkin S, Yaffe M: A longitudinal study of the effects of menopause on mammographic features. Cancer Epidemiol Biomarkers Prev. 2002, 11: 1048-1053.PubMed Boyd N, Martin L, Stone J, Little L, Minkin S, Yaffe M: A longitudinal study of the effects of menopause on mammographic features. Cancer Epidemiol Biomarkers Prev. 2002, 11: 1048-1053.PubMed
14.
go back to reference Boyd NF, Martin LJ, Sun L, Guo H, Chiarelli A, Hislop G, Yaffe M, Minkin S: Body size, mammographic density, and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2006, 15: 2086-2092. 10.1158/1055-9965.EPI-06-0345.CrossRefPubMed Boyd NF, Martin LJ, Sun L, Guo H, Chiarelli A, Hislop G, Yaffe M, Minkin S: Body size, mammographic density, and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2006, 15: 2086-2092. 10.1158/1055-9965.EPI-06-0345.CrossRefPubMed
15.
go back to reference Butler LM, Gold EB, Greendale GA, Crandall CJ, Modugno F, Oestreicher N, Quesenberry CP, Habel LA: Menstrual and reproductive factors in relation to mammographic density: the Study of Women's Health Across the Nation (SWAN). Breast Cancer Res Treat. 2008, 112: 165-174. 10.1007/s10549-007-9840-0.CrossRefPubMed Butler LM, Gold EB, Greendale GA, Crandall CJ, Modugno F, Oestreicher N, Quesenberry CP, Habel LA: Menstrual and reproductive factors in relation to mammographic density: the Study of Women's Health Across the Nation (SWAN). Breast Cancer Res Treat. 2008, 112: 165-174. 10.1007/s10549-007-9840-0.CrossRefPubMed
16.
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.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.CrossRefPubMed
17.
go back to reference Vachon CM, Kuni CC, Anderson K, Anderson VE, Sellers TA: Association of mammographically defined percent breast density with epidemiologic risk factors for breast cancer (United States). Cancer Causes Control. 2000, 11: 653-662. 10.1023/A:1008926607428.CrossRefPubMed Vachon CM, Kuni CC, Anderson K, Anderson VE, Sellers TA: Association of mammographically defined percent breast density with epidemiologic risk factors for breast cancer (United States). Cancer Causes Control. 2000, 11: 653-662. 10.1023/A:1008926607428.CrossRefPubMed
18.
go back to reference Warwick J, Pinney E, Warren RM, Duffy SW, Howell A, Wilson M, Cuzick J: Breast density and breast cancer risk factors in a high-risk population. Breast. 2003, 12: 10-16. 10.1016/S0960-9776(02)00212-6.CrossRefPubMed Warwick J, Pinney E, Warren RM, Duffy SW, Howell A, Wilson M, Cuzick J: Breast density and breast cancer risk factors in a high-risk population. Breast. 2003, 12: 10-16. 10.1016/S0960-9776(02)00212-6.CrossRefPubMed
19.
go back to reference Poole AJ, Li Y, Kim Y, Lin SC, Lee WH, Lee EY: Prevention of Brca1-mediated mammary tumorigenesis in mice by a progesterone antagonist. Science. 2006, 314: 1467-1470. 10.1126/science.1130471.CrossRefPubMed Poole AJ, Li Y, Kim Y, Lin SC, Lee WH, Lee EY: Prevention of Brca1-mediated mammary tumorigenesis in mice by a progesterone antagonist. Science. 2006, 314: 1467-1470. 10.1126/science.1130471.CrossRefPubMed
20.
go back to reference Huo Z, Giger ML, Wolverton DE, Zhong W, Cumming S, Olopade OI: Computerized analysis of mammographic parenchymal patterns for breast cancer risk assessment: feature selection. Med Phys. 2000, 27: 4-12. 10.1118/1.598851.CrossRefPubMed Huo Z, Giger ML, Wolverton DE, Zhong W, Cumming S, Olopade OI: Computerized analysis of mammographic parenchymal patterns for breast cancer risk assessment: feature selection. Med Phys. 2000, 27: 4-12. 10.1118/1.598851.CrossRefPubMed
21.
go back to reference Huo Z, Giger ML, Olopade OI, Wolverton DE, Weber BL, Metz CE, Zhong W, Cummings SA: Computerized analysis of digitized mammograms of BRCA1 and BRCA2 gene mutation carriers. Radiology. 2002, 225: 519-526. 10.1148/radiol.2252010845.CrossRefPubMed Huo Z, Giger ML, Olopade OI, Wolverton DE, Weber BL, Metz CE, Zhong W, Cummings SA: Computerized analysis of digitized mammograms of BRCA1 and BRCA2 gene mutation carriers. Radiology. 2002, 225: 519-526. 10.1148/radiol.2252010845.CrossRefPubMed
22.
go back to reference Li H, Giger ML, Olopade OI, Margolis A, Lan L, Chinander MR: Computerized texture analysis of mammographic parenchymal patterns of digitized mammograms. Acad Radiol. 2005, 12: 863-873. 10.1016/j.acra.2005.03.069.CrossRefPubMed Li H, Giger ML, Olopade OI, Margolis A, Lan L, Chinander MR: Computerized texture analysis of mammographic parenchymal patterns of digitized mammograms. Acad Radiol. 2005, 12: 863-873. 10.1016/j.acra.2005.03.069.CrossRefPubMed
23.
go back to reference Li H, Giger ML, Olopade OI, Lan L: Fractal analysis of mammographic parenchymal patterns in breast cancer risk assessment. Acad Radiol. 2007, 14: 513-521. 10.1016/j.acra.2007.02.003.CrossRefPubMed Li H, Giger ML, Olopade OI, Lan L: Fractal analysis of mammographic parenchymal patterns in breast cancer risk assessment. Acad Radiol. 2007, 14: 513-521. 10.1016/j.acra.2007.02.003.CrossRefPubMed
24.
go back to reference Duffy SW, Nagtegaal ID, Astley SM, Gillan MG, McGee MA, Boggis CR, Wilson M, Beetles UM, Griffiths MA, Jain AK, Johnson J, Roberts R, Deans H, Duncan KA, Iyengar G, Griffiths PM, Warwick J, Cuzick J, Gilbert FJ: Visually assessed breast density, breast cancer risk and the importance of the craniocaudal view. Breast Cancer Res. 2008, 10: R64-10.1186/bcr2123.CrossRefPubMedPubMedCentral Duffy SW, Nagtegaal ID, Astley SM, Gillan MG, McGee MA, Boggis CR, Wilson M, Beetles UM, Griffiths MA, Jain AK, Johnson J, Roberts R, Deans H, Duncan KA, Iyengar G, Griffiths PM, Warwick J, Cuzick J, Gilbert FJ: Visually assessed breast density, breast cancer risk and the importance of the craniocaudal view. Breast Cancer Res. 2008, 10: R64-10.1186/bcr2123.CrossRefPubMedPubMedCentral
Metadata
Title
Assessing the usefulness of a novel MRI-based breast density estimation algorithm in a cohort of women at high genetic risk of breast cancer: the UK MARIBS study
Authors
Deborah J Thompson
Martin O Leach
Gek Kwan-Lim
Simon A Gayther
Susan J Ramus
Iqbal Warsi
Fiona Lennard
Michael Khazen
Emilie Bryant
Sadie Reed
Caroline RM Boggis
D Gareth Evans
Rosalind A Eeles
Douglas F Easton
Ruth ML Warren
The UK study of MRI screening for breast cancer in women at high risk (MARIBS)
Publication date
01-12-2009
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 6/2009
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2447

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