Breast cancer risk factors and a novel measure of volumetric breast density: cross-sectional study

We conducted a cross-sectional study nested within a prospective cohort of breast cancer risk factors and two novel measures of breast density volume among 590 women who had attended Glasgow University (1948–1968), replied to a postal questionnaire (2001) and attended breast screening in Scotland (1989–2002). Volumetric breast density was estimated using a fully automated computer programme applied to digitised film-screen mammograms, from medio-lateral oblique mammograms at the first-screening visit. This measured the proportion of the breast volume composed of dense (non-fatty) tissue (Standard Mammogram Form (SMF)%) and the absolute volume of this tissue (SMF volume, cm3). Median age at first screening was 54.1 years (range: 40.0–71.5), median SMF volume 70.25 cm3 (interquartile range: 51.0–103.0) and mean SMF% 26.3%, s.d.=8.0% (range: 12.7–58.8%). Age-adjusted logistic regression models showed a positive relationship between age at last menstrual period and SMF%, odds ratio (OR) per year later: 1.05 (95% confidence interval: 1.01–1.08, P=0.004). Number of pregnancies was inversely related to SMF volume, OR per extra pregnancy: 0.78 (0.70–0.86, P<0.001). There was a suggestion of a quadratic relationship between birthweight and SMF%, with lowest risks in women born under 2.5 and over 4 kg. Body mass index (BMI) at university (median age 19) and in 2001 (median age 62) were positively related to SMF volume, OR per extra kg m−2 1.21 (1.15–1.28) and 1.17 (1.09–1.26), respectively, and inversely related to SMF%, OR per extra kg m−2 0.83 (0.79–0.88) and 0.82 (0.76–0.88), respectively, P<0.001. Standard Mammogram Form% and absolute SMF volume are related to several, but not all, breast cancer risk factors. In particular, the positive relationship between BMI and SMF volume suggests that volume of dense breast tissue will be a useful marker in breast cancer studies

Epidemiologic Studies of Isoflavones & Mammographic Density

Isoflavones, phytoestrogens in soy beans with estrogen-like properties, have been examined for their cancer protective effects. Mammographic density is a strong predictor of breast cancer. This review summarizes studies that have examined the association between isoflavones and breast density. Observational investigations in Hawaii and Singapore suggest slightly lower breast density among women of Asian descent with regular soy intake, but two larger studies from Japan and Singapore did not observe a protective effect. The findings from seven randomized trials with primarily Caucasian women indicate that soy or isoflavones do not modify mammographic density. Soy foods and isoflavone supplements within a nutritional range do not appear to modify breast cancer risk as assessed by mammographic density

Prediction of near-term risk of developing breast cancer using computerized features from bilateral mammograms

abstract: Asymmetry of bilateral mammographic tissue density and patterns is a potentially strong indicator of having or developing breast abnormalities or early cancers. The purpose of this study is to design and test the global asymmetry features from bilateral mammograms to predict the near-term risk of women developing detectable high risk breast lesions or cancer in the next sequential screening mammography examination. The image dataset includes mammograms acquired from 90 women who underwent routine screening examinations, all interpreted as negative and not recalled by the radiologists during the original screening procedures. A computerized breast cancer risk analysis scheme using four image processing modules, including image preprocessing, suspicious region segmentation, image feature extraction, and classification was designed to detect and compute image feature asymmetry between the left and right breasts imaged on the mammograms. The highest computed area under curve (AUC) is 0.754 ± 0.024 when applying the new computerized aided diagnosis (CAD) scheme to our testing dataset. The positive predictive value and the negative predictive value were 0.58 and 0.80, respectively.NOTICE: this is the author's version of a work that was accepted for publication in . Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in , 38, 348-357. DOI: 10.1016/j.compmedimag.2014.03.00

Mammographic density, breast cancer risk and risk prediction

In this review, we examine the evidence for mammographic density as an independent risk factor for breast cancer, describe the risk prediction models that have incorporated density, and discuss the current and future implications of using mammographic density in clinical practice. Mammographic density is a consistent and strong risk factor for breast cancer in several populations and across age at mammogram. Recently, this risk factor has been added to existing breast cancer risk prediction models, increasing the discriminatory accuracy with its inclusion, albeit slightly. With validation, these models may replace the existing Gail model for clinical risk assessment. However, absolute risk estimates resulting from these improved models are still limited in their ability to characterize an individual's probability of developing cancer. Promising new measures of mammographic density, including volumetric density, which can be standardized using full-field digital mammography, will likely result in a stronger risk factor and improve accuracy of risk prediction models

Effective radiation attenuation calibration for breast density: compression thickness influences and correction

<p>Abstract</p> <p>Background</p> <p>Calibrating mammograms to produce a standardized breast density measurement for breast cancer risk analysis requires an accurate spatial measure of the compressed breast thickness. Thickness inaccuracies due to the nominal system readout value and compression paddle orientation induce unacceptable errors in the calibration.</p> <p>Method</p> <p>A thickness correction was developed and evaluated using a fully specified two-component surrogate breast model. A previously developed calibration approach based on effective radiation attenuation coefficient measurements was used in the analysis. Water and oil were used to construct phantoms to replicate the deformable properties of the breast. Phantoms consisting of measured proportions of water and oil were used to estimate calibration errors without correction, evaluate the thickness correction, and investigate the reproducibility of the various calibration representations under compression thickness variations.</p> <p>Results</p> <p>The average thickness uncertainty due to compression paddle warp was characterized to within 0.5 mm. The relative calibration error was reduced to 7% from 48-68% with the correction. The normalized effective radiation attenuation coefficient (planar) representation was reproducible under intra-sample compression thickness variations compared with calibrated volume measures.</p> <p>Conclusion</p> <p>Incorporating this thickness correction into the rigid breast tissue equivalent calibration method should improve the calibration accuracy of mammograms for risk assessments using the reproducible planar calibration measure.</p

Diagnostic Reference Levels for digital mammography in Australia

Aims: In 3 phases, this thesis explores: radiation doses delivered to women during mammography, methods to estimate mean glandular dose (MGD), and the use of mammographic breast density (MBD) in MGD calculations. Firstly, it examines Diagnostic reference levels (DRLs) for digital mammography in Australia, with novel focus on the use of compressed breast thickness (CBT) and detector technologies as a guide when determining patient derived DRLs. Secondly, it analyses the agreement between Organ Dose estimated by different digital mammography units and calculated MGD for clinical data. Thirdly, it explores the novel use of MBD in MGD calculations, suggesting a new dose estimation called the actual glandular dose (AGD), and compares MGD to AGD. Methods: DICOM headers were extracted from 52405 anonymised mammograms using 3rd party software. Exposure and QA information were utilised to calculate MGD using 3 methods. LIBRA software was used to estimate MBD for 31097 mammograms. Median, 75th and 95th percentiles were calculated across MGDs obtained for all included data and according to 9 CBT ranges, average population CBT, and for 3 detector technologies. The significance of the differences, correlations, and agreement between MGDs for different CBT ranges, calculation methods, and different density estimation methods were analysed. Conclusions: This thesis have recommended DRLs for mammography in Australia, it shows that MGD is dependent upon CBT and detector technology, hence DRLs were presented as a table for different CBTs and detectors. The work also shows that Organ Doses reported by vendors vary from that calculated using established methodologies. Data produced also show that the use of MGD calculated using standardised glandularities underestimates dose at lower CBTs compared to AGD by up to 10%, hence, underestimating radiation risk. Finally, AGD was proposed; it considers differences in breast composition for individualised radiation-induced risk assessment