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      Area and Volumetric Density Estimation in Processed Full-Field Digital Mammograms for Risk Assessment of Breast Cancer

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          Abstract

          Introduction

          Mammographic density, the white radiolucent part of a mammogram, is a marker of breast cancer risk and mammographic sensitivity. There are several means of measuring mammographic density, among which are area-based and volumetric-based approaches. Current volumetric methods use only unprocessed, raw mammograms, which is a problematic restriction since such raw mammograms are normally not stored. We describe fully automated methods for measuring both area and volumetric mammographic density from processed images.

          Methods

          The data set used in this study comprises raw and processed images of the same view from 1462 women. We developed two algorithms for processed images, an automated area-based approach (CASAM-Area) and a volumetric-based approach (CASAM-Vol). The latter method was based on training a random forest prediction model with image statistical features as predictors, against a volumetric measure, Volpara, for corresponding raw images. We contrast the three methods, CASAM-Area, CASAM-Vol and Volpara directly and in terms of association with breast cancer risk and a known genetic variant for mammographic density and breast cancer, rs10995190 in the gene ZNF365. Associations with breast cancer risk were evaluated using images from 47 breast cancer cases and 1011 control subjects. The genetic association analysis was based on 1011 control subjects.

          Results

          All three measures of mammographic density were associated with breast cancer risk and rs10995190 (p<0.025 for breast cancer risk and p<1×10 −6 for rs10995190). After adjusting for one of the measures there remained little or no evidence of residual association with the remaining density measures (p>0.10 for risk, p>0.03 for rs10995190).

          Conclusions

          Our results show that it is possible to obtain reliable automated measures of volumetric and area mammographic density from processed digital images. Area and volumetric measures of density on processed digital images performed similar in terms of risk and genetic association.

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          Most cited references19

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          Association of mammographically defined percent breast density with epidemiologic risk factors for breast cancer (United States).

          Mammographically defined percent breast density is an important risk factor for breast cancer, but the epidemiology of this trait is poorly understood. Although several studies have investigated the associations between reproductive factors and density, few data are available on the associations of breast density and waist-to-hip ratio (WHR), physical activity, education, alcohol and smoking. We investigated the associations of known and suspected breast cancer risk factors with breast density in a large breast cancer family study. Information was collected on members of 426 families through telephone interviews, mailed questionnaires and mammography. Mammographic films on 1900 women were digitized and breast density was estimated in discrete five-unit increments by one radiologist. Analysis of covariance techniques were used and all analyses were performed stratified by menopausal status. Similar to other reports, nulliparity, late age at first birth, younger age and lower body mass index were associated with increased percent density in both premenopausal and postmenopausal women, and hormone replacement therapy among postmenopausal women. Higher levels of alcohol consumption and low WHR were associated with increased percent density among both premenopausal and postmenopausal women (differences of 3-11% between high and low categories). However, smoking and education were inversely associated with percent density among premenopausal (p = 0.004 and p = 0.003, respectively) but not postmenopausal women (p = 0.52 and p = 0.90). Physical activity was not associated with percent density in either stratum (p values > 0.25). Combined, these factors explained approximately 37% of the variability in the percent density measure in premenopausal women and 19% in postmenopausal women. Many of these factors may potentially affect breast cancer risk through their effect on percent breast density.
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            Volume of mammographic density and risk of breast cancer.

            Assessing the volume of mammographic density might more accurately reflect the amount of breast volume at risk of malignant transformation and provide a stronger indication of risk of breast cancer than methods based on qualitative scores or dense breast area. We prospectively collected mammograms for women undergoing screening mammography. We determined the diagnosis of subsequent invasive or ductal carcinoma in situ for 275 cases, selected 825 controls matched for age, ethnicity, and mammography system, and assessed three measures of breast density: percent dense area, fibroglandular volume, and percent fibroglandular volume. After adjustment for familial breast cancer history, body mass index, history of breast biopsy, and age at first live birth, the ORs for breast cancer risk in the highest versus lowest measurement quintiles were 2.5 (95% CI: 1.5-4.3) for percent dense area, 2.9 (95% CI: 1.7-4.9) for fibroglandular volume, and 4.1 (95% CI: 2.3-7.2) for percent fibroglandular volume. Net reclassification indexes for density measures plus risk factors versus risk factors alone were 9.6% (P = 0.07) for percent dense area, 21.1% (P = 0.0001) for fibroglandular volume, and 14.8% (P = 0.004) for percent fibroglandular volume. Fibroglandular volume improved the categorical risk classification of 1 in 5 women for both women with and without breast cancer. Volumetric measures of breast density are more accurate predictors of breast cancer risk than risk factors alone and than percent dense area. Risk models including dense fibroglandular volume may more accurately predict breast cancer risk than current risk models. ©2011 AACR
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              Volumetric breast density estimation from full-field digital mammograms.

              A method is presented for estimation of dense breast tissue volume from mammograms obtained with full-field digital mammography (FFDM). The thickness of dense tissue mapping to a pixel is determined by using a physical model of image acquisition. This model is based on the assumption that the breast is composed of two types of tissue, fat and parenchyma. Effective linear attenuation coefficients of these tissues are derived from empirical data as a function of tube voltage (kVp), anode material, filtration, and compressed breast thickness. By employing these, tissue composition at a given pixel is computed after performing breast thickness compensation, using a reference value for fatty tissue determined by the maximum pixel value in the breast tissue projection. Validation has been performed using 22 FFDM cases acquired with a GE Senographe 2000D by comparing the volume estimates with volumes obtained by semi-automatic segmentation of breast magnetic resonance imaging (MRI) data. The correlation between MRI and mammography volumes was 0.94 on a per image basis and 0.97 on a per patient basis. Using the dense tissue volumes from MRI data as the gold standard, the average relative error of the volume estimates was 13.6%.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                20 October 2014
                : 9
                : 10
                : e110690
                Affiliations
                [1 ]Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
                [2 ]Human Genetics, Genome Institute of Singapore, Singapore, Singapore
                [3 ]Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom
                University of Texas School of Public Health, United States of America
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: KH AC PH KC. Performed the experiments: AC KH. Analyzed the data: AC KH. Contributed reagents/materials/analysis tools: PH ME. Contributed to the writing of the manuscript: AC KH PH KC ME DE JL.

                Article
                PONE-D-14-25713
                10.1371/journal.pone.0110690
                4203856
                25329322
                6e1f8214-849c-4668-b838-0040a9d9d203
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 9 June 2014
                : 15 September 2014
                Page count
                Pages: 10
                Funding
                This work was supported by the Swedish Research Council [grant number 521-2011-3205], the Swedish Cancer Society [contract number 11 0600] and the Swedish E-Science Research Centre. The KARMA study was supported by Märit and Hans Rausings Initiative against Breast Cancer and the Cancer Risk Prediction Center (CRisP: www.crispcenter.org), a Linneus Centre [contract number 70867902] financed by the Swedish Research Council. Jingmei Li is supported by the 2nd Joint Council Office (JCO) Career Development Grant (13302EG065). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Diagnostic Medicine
                Diagnostic Radiology
                Mammography
                Epidemiology
                Biomarker Epidemiology
                Cancer Epidemiology
                Oncology
                Cancers and Neoplasms
                Breast Tumors
                Breast Cancer
                Radiology and Imaging
                Research and Analysis Methods
                Imaging Techniques
                Custom metadata
                The authors confirm that all data underlying the findings are fully available without restriction. All underlying numerical measurements and data that have been used to derive the results in this study are available in the Supporting Information files. Mammogram images can be made available upon request to: http://karmastudy.org/data-access/.

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