Purpose:The amount of fibroglandular tissue content in the breast as estimated mammographically, commonly referred to as breast percent density (PD%), is one of the most significant risk factors for developing breast cancer. Approaches to quantify breast density commonly focus on either semiautomated methods or visual assessment, both of which are highly subjective. Furthermore, most studies published to date investigating computer-aided assessment of breast PD% have been performed using digitized screen-film mammograms, while digital mammography is increasingly replacing screenfilm mammography in breast cancer screening protocols. Digital mammography imaging generates two types of images for analysis, raw (i.e., "FOR PROCESSING") and vendor postprocessed (i.e., "FOR PRESENTATION"), of which postprocessed images are commonly used in clinical practice. Development of an algorithm which effectively estimates breast PD% in both raw and postprocessed digital mammography images would be beneficial in terms of direct clinical application and retrospective analysis. Methods: This work proposes a new algorithm for fully automated quantification of breast PD% based on adaptive multiclass fuzzy c-means (FCM) clustering and support vector machine (SVM) classification, optimized for the imaging characteristics of both raw and processed digital mammography images as well as for individual patient and image characteristics. Our algorithm first delineates the breast region within the mammogram via an automated thresholding scheme to identify background air followed by a straight line Hough transform to extract the pectoral muscle region. The algorithm then applies adaptive FCM clustering based on an optimal number of clusters derived from image properties of the specific mammogram to subdivide the breast into regions of similar graylevel intensity. Finally, a SVM classifier is trained to identify which clusters within the breast tissue are likely fibroglandular, which are then aggregated into a final dense tissue segmentation that is used to compute breast PD%. Our method is validated on a group of 81 women for whom bilateral, mediolateral oblique, raw and processed screening digital mammograms were available, and agreement is assessed with both continuous and categorical density estimates made by a trained breast-imaging radiologist. Results: Strong association between algorithm-estimated and radiologist-provided breast PD% was detected for both raw (r = 0.82, p < 0.001) and processed (r = 0.85, p < 0.001) digital mammograms on a per-breast basis. Stronger agreement was found when overall breast density was assessed on a per-woman basis for both raw (r = 0.85, p < 0.001) and processed (0.89, p < 0.001) mammograms. Strong agreement between categorical density estimates was also seen (weighted Cohen's κ ≥ 0.79). Repeated measures analysis of variance demonstrated no statistically significant differences between the PD% estimates (p > 0.1) due to either presentation of the image (raw vs processed) or method of PD% assessment (ra...

Purpose To present a method for identifying intrinsic imaging phenotypes in breast cancer tumors and to investigate their association with prognostic gene expression profiles. Materials and Methods The authors retrospectively analyzed dynamic contrast material–enhanced (DCE) magnetic resonance (MR) images of the breast in 56 women (mean age, 55.6 years; age range, 37–74 years) diagnosed with estrogen receptor–positive breast cancer between 2005 and 2010. The study was approved by the institutional review board and compliant with HIPAA. The requirement to obtain informed consent was waived. Primary tumors were assayed with a validated gene expression assay that provides a score for the likelihood of recurrence. A multiparametric imaging phenotype vector was extracted for each tumor by using quantitative morphologic, kinetic, and spatial heterogeneity features. Multivariate linear regression was performed to test associations between DCE MR imaging features and recurrence likelihood. To identify intrinsic imaging phenotypes, hierarchical clustering was performed on the extracted feature vectors. Multivariate logistic regression was used to classify tumors at high versus low or medium risk of recurrence. To determine the additional value of intrinsic phenotypes, the phenotype category was tested as an additional variable. Receiver operating characteristic analysis and the area under the receiver operating characteristic curve (Az) were used to assess classification performance. Results There was a moderate correlation (r = 0.71, R2 = 0.50, P < .001) between DCE MR imaging features and the recurrence score. DCE MR imaging features were predictive of recurrence risk as determined by the surrogate assay, with an Az of 0.77 (P < .01). Four dominant imaging phenotypes were detected, with two including only low- and medium-risk tumors. When the phenotype category was used as an additional variable, the Az increased to 0.82 (P < .01). Conclusion Intrinsic imaging phenotypes exist for breast cancer tumors and correlate with recurrence likelihood as determined with gene expression profiling. These imaging biomarkers could ultimately help guide treatment decisions.

The growth of multiparametric imaging protocols has paved the way for quantitative imaging phenotypes that predict treatment response and clinical outcome, reflect underlying cancer molecular characteristics and spatiotemporal heterogeneity, and can guide personalized treatment planning. This growth has underlined the need for efficient quantitative analytics to derive high-dimensional imaging signatures of diagnostic and predictive value in this emerging era of integrated precision diagnostics. This paper presents cancer imaging phenomics toolkit (CaPTk), a new and dynamically growing software platform for analysis of radiographic images of cancer, currently focusing on brain, breast, and lung cancer. CaPTk leverages the value of quantitative imaging analytics along with machine learning to derive phenotypic imaging signatures, based on two-level functionality. First, image analysis algorithms are used to extract comprehensive panels of diverse and complementary features, such as multiparametric intensity histogram distributions, texture, shape, kinetics, connectomics, and spatial patterns. At the second level, these quantitative imaging signatures are fed into multivariate machine learning models to produce diagnostic, prognostic, and predictive biomarkers. Results from clinical studies in three areas are shown: (i) computational neuro-oncology of brain gliomas for precision diagnostics, prediction of outcome, and treatment planning; (ii) prediction of treatment response for breast and lung cancer, and (iii) risk assessment for breast cancer.

BackgroundThe assessment of a woman’s risk for developing breast cancer has become increasingly important for establishing personalized screening recommendations and forming preventive strategies. Studies have consistently shown a strong relationship between breast cancer risk and mammographic parenchymal patterns, typically assessed by percent mammographic density. This paper will review the advancing role of mammographic texture analysis as a potential novel approach to characterize the breast parenchymal tissue to augment conventional density assessment in breast cancer risk estimation.Main textThe analysis of mammographic texture provides refined, localized descriptors of parenchymal tissue complexity. Currently, there is growing evidence in support of textural features having the potential to augment the typically dichotomized descriptors (dense or not dense) of area or volumetric measures of breast density in breast cancer risk assessment. Therefore, a substantial research effort has been devoted to automate mammographic texture analysis, with the aim of ultimately incorporating such quantitative measures into breast cancer risk assessment models. In this paper, we review current and emerging approaches in this field, summarizing key methodological details and related studies using novel computerized approaches. We also discuss research challenges for advancing the role of parenchymal texture analysis in breast cancer risk stratification and accelerating its clinical translation.ConclusionsThe objective is to provide a comprehensive reference for researchers in the field of parenchymal pattern analysis in breast cancer risk assessment, while indicating key directions for future research.

Background About half of US states currently require radiology facilities to disclose mammographic breast density to women, often with language recommending discussion of supplemental screening options for women with dense breasts. Objective To examine variation in breast density assessment across radiologists in clinical practice. Design Cross-sectional and longitudinal analyses of prospectively collected observational data. Setting Thirty radiology facilities within the three breast cancer screening research centers of the Population-based Research Optimizing Screening through Personalized Regimens (PROSPR) consortium. Participants Radiologists who interpreted ≥500 screening mammograms during 2011–2013 (N=83). Data on 216,783 screening mammograms from 145,123 woman aged 40–89 years were included. Measurements Mammographic breast density as clinically recorded using the four Breast Imaging-Reporting and Data System density categories (heterogeneously dense and extremely dense categories were considered “dense” for analyses); patient age, race, and body mass index (BMI). Results Overall, 36.9% of mammograms were rated as dense. Across radiologists, this percentage ranged from 6.3% to 84.5% (median 38.7%, interquartile range 22.0%), with multivariable adjustment for patient characteristics having little impact (interquartile range 20.9%). Examination of patient subgroups revealed that variation in density assessment across radiologists was pervasive in all but the most extreme patient age and BMI combinations. Among women undergoing consecutive exams interpreted by different radiologists, 17.2% (5,909/34,271) had discordant assessments of dense/non-dense status. Limitations Quantitative measures of mammographic breast density were not available for comparison. Conclusions There is wide variation in density assessment across radiologists that should be carefully considered by providers and policy makers when considering supplemental screening strategies. The likelihood of a woman being told she has dense breasts varies substantially according to which radiologist interprets her mammogram. Funding Source National Institutes of Health

IntroductionMammography screening results in a significant number of false-positives. The use of pretest breast cancer risk factors to guide follow-up of abnormal mammograms could improve the positive predictive value of screening. We evaluated the use of the Gail model, body mass index (BMI), and genetic markers to predict cancer diagnosis among women with abnormal mammograms. We also examined the extent to which pretest risk factors could reclassify women without cancer below the biopsy threshold.MethodsWe recruited a prospective cohort of women referred for biopsy with abnormal (BI-RADS 4) mammograms according to the American College of Radiology’s Breast Imaging-Reporting and Data System (BI-RADS). Breast cancer risk factors were assessed prior to biopsy. A validated panel of 12 single-nucleotide polymorphisms (SNPs) associated with breast cancer were measured. Logistic regression was used to assess the association of Gail risk factors, BMI and SNPs with cancer diagnosis (invasive or ductal carcinoma in situ). Model discrimination was assessed using the area under the receiver operating characteristic curve, and calibration was assessed using the Hosmer-Lemeshow goodness-of-fit test. The distribution of predicted probabilities of a cancer diagnosis were compared for women with or without breast cancer.ResultsIn the multivariate model, age (odds ratio (OR) = 1.05; 95% confidence interval (CI), 1.03 to 1.08; P < 0.001), SNP panel relative risk (OR = 2.30; 95% CI, 1.06 to 4.99, P = 0.035) and BMI (≥30 kg/m2 versus <25 kg/m2; OR = 2.20; 95% CI, 1.05 to 4.58; P = 0.036) were significantly associated with breast cancer diagnosis. Older women were more likely than younger women to be diagnosed with breast cancer. The SNP panel relative risk remained strongly associated with breast cancer diagnosis after multivariable adjustment. Higher BMI was also strongly associated with increased odds of a breast cancer diagnosis. Obese women (OR = 2.20; 95% CI, 1.05 to 4.58; P = 0.036) had more than twice the odds of cancer diagnosis compared to women with a BMI <25 kg/m2. The SNP panel appeared to have predictive ability among both white and black women.ConclusionsBreast cancer risk factors, including BMI and genetic markers, are predictive of cancer diagnosis among women with BI-RADS 4 mammograms. Using pretest risk factors to guide follow-up of abnormal mammograms could reduce the burden of false-positive mammograms.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-014-0509-4) contains supplementary material, which is available to authorized users.

Our data support the clinical implementation of DBT in breast cancer screening; however, larger prospective trials are needed to validate our findings in specific patient subgroups.

Purpose: Mammographic percent density (PD%) is known to be a strong risk factor for breast cancer. Recent studies also suggest that parenchymal texture features, which are more granular descriptors of the parenchymal pattern, can provide additional information about breast cancer risk. To date, most studies have measured mammographic texture within selected regions of interest (ROIs) in the breast, which cannot adequately capture the complexity of the parenchymal pattern throughout the whole breast. To better characterize patterns of the parenchymal tissue, the authors have developed a fully automated software pipeline based on a novel lattice-based strategy to extract a range of parenchymal texture features from the entire breast region. Methods: Digital mammograms from 106 cases with 318 age-matched controls were retrospectively analyzed. The lattice-based approach is based on a regular grid virtually overlaid on each mammographic image. Texture features are computed from the intersection (i.e., lattice) points of the grid lines within the breast, using a local window centered at each lattice point. Using this strategy, a range of statistical (gray-level histogram, co-occurrence, and run-length) and structural (edge-enhancing, local binary pattern, and fractal dimension) features are extracted. To cover the entire breast, the size of the local window for feature extraction is set equal to the lattice grid spacing and optimized experimentally by evaluating different windows sizes. The association between their lattice-based texture features and breast cancer was evaluated using logistic regression with leave-one-out cross validation and further compared to that of breast PD% and commonly used single-ROI texture features extracted from the retroareolar or the central breast region. Classification performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC). DeLong's test was used to compare the different ROCs in terms of AUC performance. Results: The average univariate performance of the lattice-based features is higher when extracted from smaller than larger window sizes. While not every individual texture feature is superior to breast PD% (AUC: 0.59, STD: 0.03), their combination in multivariate analysis has significantly better performance (AUC: 0.85, STD: 0.02, p < 0.001). The lattice-based texture features also outperform the single-ROI texture features when extracted from the retroareolar or the central breast region (AUC: 0.60-0.74, STD: 0.03). Adding breast PD% does not make a significant performance improvement to the lattice-based texture features or the single-ROI features (p > 0.05). Conclusions: The proposed lattice-based strategy for mammographic texture analysis enables to characterize the parenchymal pattern over the entire breast. As such, these features provide richer information compared to currently used descriptors and may ultimately improve breast cancer risk assessment. Larger studies are warranted to validate these findings and also compare...