Background risk of breast cancer and the association between physical activity and mammographic density

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Mammographic density and breast cancer risk in breast screening assessment cases and women with a family history of breast cancer.

BACKGROUND: Mammographic density has been shown to be a strong independent predictor of breast cancer and a causative factor in reducing the sensitivity of mammography. There remain questions as to the use of mammographic density information in the context of screening and risk management, and of the association with cancer in populations known to be at increased risk of breast cancer. AIM: To assess the association of breast density with presence of cancer by measuring mammographic density visually as a percentage, and with two automated volumetric methods, Quantra™ and VolparaDensity™. METHODS: The TOMosynthesis with digital MammographY (TOMMY) study of digital breast tomosynthesis in the Breast Screening Programme of the National Health Service (NHS) of the United Kingdom (UK) included 6020 breast screening assessment cases (of whom 1158 had breast cancer) and 1040 screened women with a family history of breast cancer (of whom two had breast cancer). We assessed the association of each measure with breast cancer risk in these populations at enhanced risk, using logistic regression adjusted for age and total breast volume as a surrogate for body mass index (BMI). RESULTS: All density measures showed a positive association with presence of cancer and all declined with age. The strongest effect was seen with Volpara absolute density, with a significant 3% (95% CI 1-5%) increase in risk per 10 cm3 of dense tissue. The effect of Volpara volumetric density on risk was stronger for large and grade 3 tumours. CONCLUSIONS: Automated absolute breast density is a predictor of breast cancer risk in populations at enhanced risk due to either positive mammographic findings or family history. In the screening context, density could be a trigger for more intensive imaging

Mammographic breast density: comparison of methods for quantitative evaluation.

PURPOSE: To evaluate the results from two software tools for measurement of mammographic breast density and compare them with observer-based scores in a large cohort of women. MATERIALS AND METHODS: Following written informed consent, a data set of 36 281 mammograms from 8867 women were collected from six United Kingdom centers in an ethically approved trial. Breast density was assessed by one of 26 readers on a visual analog scale and with two automated density tools. Mean differences were calculated as the mean of all the individual percentage differences between each measurement for each case (woman). Agreement in total breast volume, fibroglandular volume, and percentage density was assessed with the Bland-Altman method. Association with observer's scores was calculated by using the Pearson correlation coefficient (r). RESULTS: Correlation between the Quantra and Volpara outputs for total breast volume was r = 0.97 (P < .001), with a mean difference of 43.5 cm(3) for all cases representing 5.0% of the mean total breast volume. Correlation of the two measures was lower for fibroglandular volume (r = 0.86, P < .001). The mean difference was 30.3 cm(3) for all cases representing 21.2% of the mean fibroglandular tissue volume result. Quantra gave the larger value and the difference tended to increase with volume. For the two measures of percentage volume density, the mean difference was 1.61 percentage points (r = 0.78, P < .001). Comparison of observer's scores with the area-based density given by Quantra yielded a low correlation (r = 0.55, P < .001). Correlations of observer's scores with the volumetric density results gave r values of 0.60 (P < .001) and 0.63 (P < .001) for Quantra and Volpara, respectively. CONCLUSION: Automated techniques for measuring breast density show good correlation, but these are poorly correlated with observer's scores. However automated techniques do give different results that should be considered when informing patient personalized imaging. (©) RSNA, 2015 Clinical trial registration no. ISRCTN 73467396.Supported by the National Institute for Health Research’s Health Technology Assessment Programme.This is the final version of the article. It first appeared at http://pubs.rsna.org/doi/full/10.1148/radiol.1414150

Semi-automated and fully automated mammographic density measurement and breast cancer risk prediction

The task of breast density quantification is becoming increasingly relevant due to its association with breast cancer risk. In this work, a semi-automated and a fully automated tools to assess breast density from full-field digitized mammograms are presented. The first tool is based on a supervised interactive thresholding procedure for segmenting dense from fatty tissue and is used with a twofold goal: for assessing mammographic density(MD) in a more objective and accurate way than via visual-based methods and for labeling the mammograms that are later employed to train the fully automated tool. Although most automated methods rely on supervised approaches based on a global labeling of the mammogram, the proposed method relies on pixel-level labeling, allowing better tissue classification and density measurement on a continuous scale. The fully automated method presented combines a classification scheme based on local features and thresholding operations that improve the performance of the classifier. A dataset of 655 mammograms was used to test the concordance of both approaches in measuring MD. Three expert radiologists measured MD in each of the mammograms using the semi-automated tool (DM-Scan). It was then measured by the fully automated system and the correlation between both methods was computed. The relation between MD and breast cancer was then analyzed using a case-control dataset consisting of 230 mammograms. The Intraclass Correlation Coefficient (ICC) was used to compute reliability among raters and between techniques. The results obtained showed an average ICC = 0.922 among raters when using the semi-automated tool, whilst the average correlation between the semi-automated and automated measures was ICC = 0.838. In the case-control study, the results obtained showed Odds Ratios (OR) of 1.38 and 1.50 per 10% increase in MD when using the semi-automated and fully automated approaches respectively. It can therefore be concluded that the automated and semi-automated MD assessments present a good correlation. Both the methods also found an association between MD and breast cancer risk, which warrants the proposed tools for breast cancer risk prediction and clinical decision making. A full version of the DM-Scan is freely available. (C) 2014 Elsevier Ireland Ltd. All rights reserved.This work was supported by research grants from Gent per Gent Fund (EDEMAC Project); Spain's Health Research Fund (Fondo de Investigacion Santiaria) (PI060386 & FIS PS09/00790); Spanish MICINN grants TIN2009-14205-C04-02 and Consolider-Ingenio 2010: MIPRCV (CSD2007-00018); Spanish Federation of Breast Cancer Patients (Federacion Espanola de Cancer de Mama) (FECMA 485 EPY 1170-10). The English revision of this paper was funded by the Universitat Politecnica de Valencia, Spain.Llobet Azpitarte, R.; Pollán, M.; Antón Guirao, J.; Miranda-García, J.; Casals El Busto, M.; Martinez Gomez, I.; Ruiz Perales, F.... (2014). Semi-automated and fully automated mammographic density measurement and breast cancer risk prediction. Computer Methods and Programs in Biomedicine. 116(2):105-115. https://doi.org/10.1016/j.cmpb.2014.01.021S105115116

The Short-Term Effect of Weight Loss Surgery on Volumetric Breast Density and Fibroglandular Volume

Purpose: Obesity and breast density are both associated with an increased risk of breast cancer and are potentially modifiable. Weight loss surgery (WLS) causes a significant reduction in the amount of body fat and a decrease in breast cancer risk. The effect of WLS on breast density and its components has not been documented. Here, we analyze the impact of WLS on volumetric breast density (VBD) and on each of its components (fibroglandular volume and breast volume) by using three-dimensional methods. Materials and Methods: Fibroglandular volume, breast volume, and their ratio, the VBD, were calculated from mammograms before and after WLS by using Volpara™ automated software. Results: For the 80 women included, average body mass index decreased from 46.0 ± 7.22 to 33.7 ± 7.06 kg/m2. Mammograms were performed on average 11.6 ± 9.4 months before and 10.1 ± 7 months after WLS. There was a significant reduction in average breast volume (39.4 % decrease) and average fibroglandular volume (15.5 % decrease), and thus, the average VBD increased from 5.15 to 7.87 % (p < 1 × 10−9) after WLS. When stratified by menopausal status and diabetic status, VBD increased significantly in all groups but only perimenopausal and postmenopausal women and non-diabetics experienced a significant reduction in fibroglandular volume. Conclusions: Breast volume and fibroglandular volume decreased, and VBD increased following WLS, with the most significant change observed in postmenopausal women and non-diabetics. Further studies are warranted to determine how physical and biological alterations in breast density components after WLS may impact breast cancer risk.ECU Open Access Publishing Support Fun

Context-aware stacked convolutional neural networks for classification of breast carcinomas in whole-slide histopathology images

Automated classification of histopathological whole-slide images (WSI) of breast tissue requires analysis at very high resolutions with a large contextual area. In this paper, we present context-aware stacked convolutional neural networks (CNN) for classification of breast WSIs into normal/benign, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC). We first train a CNN using high pixel resolution patches to capture cellular level information. The feature responses generated by this model are then fed as input to a second CNN, stacked on top of the first. Training of this stacked architecture with large input patches enables learning of fine-grained (cellular) details and global interdependence of tissue structures. Our system is trained and evaluated on a dataset containing 221 WSIs of H&E stained breast tissue specimens. The system achieves an AUC of 0.962 for the binary classification of non-malignant and malignant slides and obtains a three class accuracy of 81.3% for classification of WSIs into normal/benign, DCIS, and IDC, demonstrating its potentials for routine diagnostics

Mammographic density and structural features can individually and jointly contribute to breast cancer risk assessment in mammography screening:a case-control study

BACKGROUND: Mammographic density is a well-established risk factor for breast cancer. We investigated the association between three different methods of measuring density or parenchymal pattern/texture on digitized film-based mammograms, and examined to what extent textural features independently and jointly with density can improve the ability to identify screening women at increased risk of breast cancer. METHODS: The study included 121 cases and 259 age- and time matched controls based on a cohort of 14,736 women with negative screening mammograms from a population-based screening programme in Denmark in 2007 (followed until 31 December 2010). Mammograms were assessed using the Breast Imaging-Reporting and Data System (BI-RADS) density classification, Tabár’s classification on parenchymal patterns and a fully automated texture quantification technique. The individual and combined association with breast cancer was estimated using binary logistic regression to calculate Odds Ratios (ORs) and the area under the receiver operating characteristic (ROC) curves (AUCs). RESULTS: Cases showed significantly higher BI-RADS and texture scores on average than controls (p < 0.001). All three methods were individually able to segregate women into different risk groups showing significant ORs for BI-RADS D3 and D4 (OR: 2.37; 1.32–4.25 and 3.93; 1.88–8.20), Tabár’s PIII and PIV (OR: 3.23; 1.20–8.75 and 4.40; 2.31–8.38), and the highest quartile of the texture score (3.04; 1.63–5.67). AUCs for BI-RADS, Tabár and the texture scores (continuous) were 0.63 (0.57–0–69), 0.65 (0.59–0–71) and 0.63 (0.57–0–69), respectively. Combining two or more methods increased model fit in all combinations, demonstrating the highest AUC of 0.69 (0.63-0.74) when all three methods were combined (a significant increase from standard BI-RADS alone). CONCLUSION: Our findings suggest that the (relative) amount of fibroglandular tissue (density) and mammographic structural features (texture/parenchymal pattern) jointly can improve risk segregation of screening women, using information already available from normal screening routine, in respect to future personalized screening strategies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2450-7) contains supplementary material, which is available to authorized users

The Relationship between Body Mass Index and Mammographic Density during a Premenopausal Weight Loss Intervention Study.

We evaluated the association between short-term change in body mass index (BMI) and breast density during a 1 year weight-loss intervention (Manchester, UK). We included 65 premenopausal women (35-45 years, ≥7 kg adult weight gain, family history of breast cancer). BMI and breast density (semi-automated area-based, automated volume-based) were measured at baseline, 1 year, and 2 years after study entry (1 year post intervention). Cross-sectional (between-women) and short-term change (within-women) associations between BMI and breast density were measured using repeated-measures correlation coefficients and multivariable linear mixed models. BMI was positively correlated with dense volume between-women (r = 0.41, 95%CI: 0.17, 0.61), but less so within-women (r = 0.08, 95%CI: -0.16, 0.28). There was little association with dense area (between-women r = -0.12, 95%CI: -0.38, 0.16; within-women r = 0.01, 95%CI: -0.24, 0.25). BMI and breast fat were positively correlated (volume: between r = 0.77, 95%CI: 0.69, 0.84, within r = 0.58, 95%CI: 0.36, 0.75; area: between r = 0.74, 95%CI: 0.63, 0.82, within r = 0.45, 95%CI: 0.23, 0.63). Multivariable models reported similar associations. Exploratory analysis suggested associations between BMI gain from 20 years and density measures (standard deviation change per +5 kg/m2 BMI: dense area: +0.61 (95%CI: 0.12, 1.09); fat volume: -0.31 (95%CI: -0.62, 0.00)). Short-term BMI change is likely to be positively associated with breast fat, but we found little association with dense tissue, although power was limited by small sample size

Mammographic density. Measurement of mammographic density

Mammographic density has been strongly associated with increased risk of breast cancer. Furthermore, density is inversely correlated with the accuracy of mammography and, therefore, a measurement of density conveys information about the difficulty of detecting cancer in a mammogram. Initial methods for assessing mammographic density were entirely subjective and qualitative; however, in the past few years methods have been developed to provide more objective and quantitative density measurements. Research is now underway to create and validate techniques for volumetric measurement of density. It is also possible to measure breast density with other imaging modalities, such as ultrasound and MRI, which do not require the use of ionizing radiation and may, therefore, be more suitable for use in young women or where it is desirable to perform measurements more frequently. In this article, the techniques for measurement of density are reviewed and some consideration is given to their strengths and limitations