BREAST-CANCER RISK AND MEASURED MAMMOGRAPHIC DENSITY

It has been well established that there is a positive correlation betw een the dense appearance of breast stroma and parenchyma on a mammogra m and the risk of breast cancer. Subjective assessment by radiologists indicated relative risks on the order of 4 to 6 for the group of wome n whose mammograms showed a density of over 75% or more of the project ed area compared to those with an absence of density. In order to obta in a more quantitative, continuous and reproducible means of estimatin g breast density, which is sensitive to small changes, we have develop ed quantitative methods for the analysis of mammographic density, whic h can be applied to digitized mammograms. These techniques have been v alidated in a nested case-control study on 708 women aged 40-59 years (on entry) who participated in a national mammographic screening study . An interactive image segmentation method and two completely automate d techniques based on image texture and grey scale histogram measures have been developed and evaluated. While our methods all show statisti cally significant risk factors for dense breasts, the interactive meth od currently provides the highest risk values (relative risk 4.0, 95% confidence interval (CI) = 2.12-7.56) compared to a measure based on t he shape of the image histogram (relative risk 3.35, 95% CI = 1.57-7.1 2) or the fractal dimension of the mammogram (relative risk 2.54, 95% CI = 1.14-5.68). All methods were highly consistent between images of the left and right breast and between the two standard views (cranio-c audal and medio-lateral oblique) of each breast, so that studies can b e done by sampling only one of the four views per examination. There i s a large number of factors in addition to breast density which affect the appearance of the mammogram. In particular, the assessment of den sity is made difficult where the breast is not uniformly compressed, e . g. at the periphery. We have designed and are currently evaluating a n image processing algorithm that effectively corrects for this proble m and have considered methods for controlling some of the variables of image acquisition in prospective studies. Measurements of breast dens ity may be helpful in assigning risk groups to women. Such measurement s might guide the frequency of mammographic screening, aid the study o f breast cancer aetiology, and be useful in monitoring possible risk-m odifying interventions. Using our techniques, we have been able to sho w that reduction of the proportion of fat in the diet can result in re ductions of breast density, although the direct connection to risk has not yet been made. The relationship between breast density and hormon e-related and genetic factors is also of great interest. It is often n ot possible or ethical to obtain mammograms on some groups of women fo r whom information on density would be very useful. This includes youn ger women as well as groups in which it would be desirable to obtain s uch information at frequent intervals. For this reason, we are explori ng the use of imaging approaches such as ultrasound and magnetic reson ance imaging, which do not require ionizing radiation, to make measure ments analogous to those now being performed by using X-ray mammograms . (C) 1998 Rapid Science Ltd.