Alan Hufton

Prevention of breast cancer in the context of a national breast screening programme.

Abstract.  Howell A, Astley S, Warwick J, Stavrinos P, Sahin S, Ingham S, McBurney H, Eckersley B, Harvie M, Wilson M, Beetles U, Warren R, Hufton A, Sergeant J, Newman W, Buchan I, Cuzick J, Evans DG (Genesis Prevention Centre and Nightingale Breast Screening Centre, University Hospital of South Manchester; School of Cancer and Enabling Sciences, University of Manchester, Manchester; Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London; School of Community Based Medicine, University of Manchester, Manchester; Genetic Medicine, Manchester Academic Health Sciences Centre, University of Manchester and Central Manchester Foundation Trust, Manchester; and Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge; UK). Prevention of breast cancer in the context of a national breast screening programme (Review). J Intern Med 2012; 271: 321–330.

A new step-wedge for the volumetric measurement of mammographic density

The volume of dense breast tissue can be calculated from an x-ray mammogram by imaging a calibrated step-wedge alongside the breast and determining the compressed breast thickness. Previously published work used a step-wedge made of PTFE with a maximum height of 35mm, length 175mm and width 15mm. Although fulfilling all theoretical requirements, it can be difficult to find space on the film for a large step-wedge when examining bigger breasts. Furthermore, the step-wedge is lead-lined, making it heavy and difficult to attach to the bucky. A more compact aluminium step-wedge has been designed to overcome these limitations, and experiments have been carried out on a prototype to evaluate its performance. Initial results show that the maximum and minimum heights of the prototype step-wedge are inadequate to sufficiently cover the range of optical densities within a breast image at the higher and lower exposures required for 6cm and 2cm Perspex (>200mAs and <40mAs respectively). However, the step increment appears to be satisfactory. Analysis of the mean pixel value and standard deviation within Regions of Interest of varying size and position indicates an optimum step length of 3mm. A new step-wedge has been constructed with an improved specification informed by the evaluation of the prototype.

Prevention of Breast Cancer on the context of National Breast Screening Programme.

Abstract.  Howell A, Astley S, Warwick J, Stavrinos P, Sahin S, Ingham S, McBurney H, Eckersley B, Harvie M, Wilson M, Beetles U, Warren R, Hufton A, Sergeant J, Newman W, Buchan I, Cuzick J, Evans DG (Genesis Prevention Centre and Nightingale Breast Screening Centre, University Hospital of South Manchester; School of Cancer and Enabling Sciences, University of Manchester, Manchester; Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London; School of Community Based Medicine, University of Manchester, Manchester; Genetic Medicine, Manchester Academic Health Sciences Centre, University of Manchester and Central Manchester Foundation Trust, Manchester; and Cambridge Breast Unit, Addenbrooke’s Hospital, Cambridge; UK). Prevention of breast cancer in the context of a national breast screening programme (Review). J Intern Med 2012; 271: 321–330.

Automated breast tissue measurement of women at increased risk of breast cancer

We have analysed data from a subgroup of thirty-nine women who had previously gained more than 10kg in adult life, and who were amongst those recruited from a family history clinic to a study examining the effects of diet and exercise on breast cancer risk. At entry to the study and after 12 months they underwent a series of investigations, including mammography during which markers were attached to the compression plate to allow accurate measurement of breast thickness. A calibrated stepwedge was placed adjacent to the breast to enable quantitative analysis. The proportions of glandular and fatty tissue were calculated at each pixel from the stepwedge and thickness data and from these, the percentage gland in the breast was computed, both by area and by volume. Statistical analysis showed that the volume of glandular tissue was not related to breast size. Over the 12 month period, the majority of the women lost weight, while some gained weight. It was found that weight change was correlated with change in the volume of fat in the breasts, with those women who lost the largest amount of weight showing the greatest reduction in volume. There was little change in volume of glandular tissue for any of the women. Percentage gland is often used as an indication of risk of developing breast cancer. These results suggest that measures of percentage of gland (e.g. Boyd groups) may be dominated by excess breast fat in overweight women.

Diffraction-enhanced imaging: improved contrast and lower dose x-ray imaging

Conventional x-ray imaging relies almost entirely on differences in the absorption of x-rays between tissues to produce contrast. While these differences are substantial between bone and soft tissue, they are very small between different soft tissue types resulting in poor visualization of soft tissues. Diffraction enhanced imaging (DEI) is currently in development by several groups as a new imaging modality that exploits information contained within the x- ray scattering distribution at low angles. We have used the SYRMEP beam line at the Elettra Synchrotron facility in Trieste, Italy to image a variety of tissue specimens, together with several phantoms. Mono-energetic photons in the range 17 keV to 25 keV were used with an analyzer crystal which diffracted the x-rays onto a detector. We have obtained some spectacular images which display remarkable contrast and resolution. The images can be processed to separate the pure absorption and pure refraction effects in a quantitative manner. These images demonstrate that DEI provides tissue morphology information not accessible with conventional radiographic imaging. The contrast caused primarily by refraction as the x-ray passes from one tissue type to another in the specimen is evident. Since x-ray refraction is much less energy dependent than absorption there is considerable potential for extremely low dose imaging. We believe that the potential of this technique is considerable and we present dat to illustrate the quality of the images.

Quantifying Breast Thickness for Density Measurement

The largest source of error in the estimation of volumetric breast density typically arises from inaccuracies in the measurement of breast thickness. We present a method which accounts for paddle tilt and show that the variation within the compressed breast region may be as much as 21.2mm in the chest wall to nipple direction. The system-indicated value of breast thickness results in an average underestimation of compressed breast volume of 10.5% which has implications for density measurement. Paddle deformation in the lateral direction is shown to be insignificant in comparison. A method of modelling the thickness at the breast periphery is presented with examples of the thickness maps generated.

Volumetric and area-based breast density measurement in the predicting risk of cancer at screening (PROCAS) study

Mammographic density, defined as the proportion of the breast area in a mammogram that contains fibroglandular tissue, is associated with risk of breast cancer. However, measures of mammographic density are subject to variation in the underlying imaging process and in the assessments of observers. Automatic volumetric measures of breast density remove much of this variability, but their association with risk is less well established. We present density measurements produced using area-based visual analogue scales (VAS) and by volumetric assessment software (QuantraTM, Hologic Inc.) in the PROCAS study. The distributions of VAS scores (n = 22 327) and volumetric quantities (n = 11 653) are given, as are their relationships for subjects with results by both (n = 11 096), but these are not directly comparable as one is area-based and the other volumetric. Inter-observer variability in visual area-based estimation is examined by a scatter plot matrix.

Feasibility and acceptability of stepwedge-based density measurement

A link between increased breast density, as visualised in mammograms, and increased risk of developing breast cancer has been established. Recently, a number of objective, quantitative methods for measuring breast density have been described. One such method requires a calibration object to be imaged alongside the breast. However, it is important that this should not interfere with the routine imaging process. In this paper, we investigate the amount of space in mammographic images which is not currently occupied by the breast or existing patient labels and markers, and which would therefore be available for imaging an additional calibration device. We do this with a view to estimating the likelihood of failure of the method, and also to determining whether, without detriment to the imaging process, a device could be permanently fixed to the breast support platform. We also examine the impact of markers attached to the compression plate on the visibility of breast tissue. The results show that our existing calibration device may be used successfully without interfering with the routine imaging process, although permanently fixing such a device may present problems in a small minority of cases, and we demonstrate that the number of cases which would fail can be reduced by using a smaller stepwedge.

Estimating Individual Cancer Risks in the UK National Breast Screening Programme: A Feasibility Study

Conventional risk models for the development of breast cancer use inputs such as age, weight, hormonal factors and family history to compute individual breast cancer risk. These are employed in the management of women at high risk. The addition of breast density as an input has been shown to improve the accuracy of such models. An improved risk model could facilitate risk-based population screening. However, in order to use breast density in risk models there is a need to employ objective methods for measuring the density. A feasibility study has been carried out to assess the practicality of using a stepwedge-based technique for measuring breast density from mammograms in the UK National Health Service Breast Screening Programme and to determine whether additional information, relevant to risk, can be collected by questionnaire. Preliminary results suggest that it is practical to use such a technique in the screening environment. In a sample of 100 women, the mean density was 27% (range 2 - 81%). A negative trend in breast density was observed with Body Mass Index.

Breast cancer diagnosis using scattered X-rays?

We have performed small angle X-ray scattering measurements at the Synchrotron Radiation Source at Daresbury to make an initial assessment of the diagnostic information obtainable from various breast tissues. These experiments have indicated that high quality interpretable diffraction data can be rapidly produced from breast core cut biopsy specimens. We have demonstrated a remarkable and systematic difference between the X-ray scattering from normal, benign and malignant breast tissue collagen. Our findings indicate that it may be possible to use molecular structure characteristics of breast tissue as novel markers of disease progression.