- Breast Density and its Implications for Your Patients
- Screening the Patient with Dense Tissue
- Measuring and Using Breast Density
Breast Density and its Implications for Your Patients
Screening mammography has made tremendous inroads into reducing the mortality rate from breast cancer over the past 30-years. During that period studies have demonstrated that it is early detection of breast cancer that is responsible for the reduction in mortality, Tabar, et al., Cancer 1999.
Unfortunately, mammography is not a perfect screening tool. Its sensitivity is highly dependant upon the radiographic density of the breast tissue. Digital mammography was intended to increase sensitivity with higher tissue densities, but the large-scale trial of digital mammography still found that mammography was less than 60% sensitive when used with women who have high-density breast tissue, vs. 98% sensitive in women with fatty breast tissue, Pisano et al., Radiology 2008.
The sensitivity problem is caused by the fact that fibroglandular tissue appears white on the mammographic image. Because cancers also appear white, the fibroglandular tissue, which is what causes tissue density, can mimic, obscure or hide breast cancers.
In addition to its confounding effect on the interpretation of mammograms, high tissue density has been determined in many studies to be an independent risk for breast cancer. Women with extremely dense breast tissue have 4-6 times more risk of getting cancer than the women whose breast tissue is mostly fat (low density), Boyd, et al., JNCI 2010. The significance of this density-related risk is so great that the American Cancer Society ranks its importance just below the risk for women who have tested positive for the BRCA 1 or 2 breast cancer genes, those with 2 or more relatives who have had pre-menopausal diagnoses of breast cancer and women with a prior history of breast cancer, ACS, Breast Cancer Facts and Figures 2009-10.
As might be expected, dense breast tissue is most often found in pre-menopausal women, and tissue density can be expected to decline from menopause on in a woman’s life. It is not, however, unusual to find post menopausal women with relatively high tissue density, and HRT and drugs like Tamoxifen have established effects on tissue density. The number of women with high tissue density is estimated at over 50% of women age 50 and under, and over 30% of women who are over the age of 50, Stomper, et al., AJR 1996. The challenge of tissue density is obviously of major importance.
Screening the Patient with Dense Tissue
While mammography may not be as effective with dense breast tissue as fatty tissue, tissue density is transparent to ultrasound and to MRI. No one has suggested that screening mammography not be continued by women with high tissue density, but in a recent large scale study, the addition of ultrasound for patients with high tissue density increased the yield of detected breast cancers by approximately 60%, Berg, et al., JAMA 2008.
Adjuvant screening is not perfect, as it results in high negative biopsy rates, but it disproportionately benefits younger women and therefore has a higher yield in terms of life years saved. Early detection is of even greater importance in this population because of the shorter sojourn time before cancers become clinically detectible, Duffy, et al., International Journal of Epidemiology 1996.
Measuring and Using Breast Density
Breast tissue density is the percentage of fibroglandular tissue that exists in the breast. Density has historically been measured by radiologists comparing the light and dark parts of a mammogram, and is reported using the BI-RADS™ density categories. Such a view works to provide a relative picture of density, but suffers from 2 significant detractions. First, it is entirely qualitative, with agreement between interpreting physicians in estimating density by quartile at only about 60% in the middle two BI-RADS density categories, in which the differentiating line between low and high tissue density is found, Nicholson, et al., Academic Radiology 2006.
The second challenge of the BI-RADS reporting system for tissue density is that it is two dimensional and the breast is a three dimensional organ that varies dramatically in shape, size and composition between individuals. An area that appears almost white on a mammogram could be a single highly dense area or it could be several densities overlying each other. Density could be evenly distributed in the breast, or the area near the skin could be dense with the center of the breast being largely replaced by fatty tissue. It is impossible to tell from simply viewing the two dimensional measurements. Kopans, Radiology 2008.
While it may be argued that sensitivity of the mammogram is a function more of the obstruction of the physician’s view of the breast in two dimensions, it is very clear that risk can only be accurately assessed with volumetric findings due to the confusion and inaccuracy that is inherent in the two dimensional projection. We know, for example, that tissue density typically decreases with age, as a woman’s breasts cease to be prepared for lactation with the onset of menopause, and the glandular tissue of the breast becomes increasingly replaced by fat. Fat replacement is observable on the mammogram, but it cannot be measured with sufficient accuracy to make subtle changes in density evident. These subtle changes, if they trend upward, may be a very early indicator of cancer development and, at the very least, should prompt an examination of non-cancer factors that can cause an increase in density (e.g., hormone replacement therapy, discontinuance of Tamoxifen or other SERM drugs, etc.).
Volpara is a technology that provides an easy to implement, objective volumetric assessment of breast tissue density. Using the “for processing” digital images from a mammogram, and a state-of-the-art algorithm developed by the world’s top imaging scientists, Volpara presents interpreting physicians with an assessment of the percentage of dense tissue contained within the breast and a mapping of that percentage to a Volpara Density Grade (VDG). The VDG is a number from 1 to 4 and the mapping has been set so as to optimize the relationship between VDG and BIRADS breast density category.
Volumetric breast tissue density is defined as the volume of fibroglandular tissue divided by the total volume of tissue within the breast. The skin should be excluded, because breast cancers occur in fibroglandular tissue, not skin and, likewise, breast fat cells do not become cancerous. The breast tissue density equation can then be written:
Volumetric Breast Density = Fibroglandular Tissue / Fibroglandular Tissue + Fat
In simple terms, determining volumetric density involves knowing the volume of the breast and defining the amount of fat within that volume. Within the image, the critical factor is being able to define a grayscale value for fat. Using new approaches to imaging physics, Volpara has been able to determine the unique “fat value” for each patient’s mammogram, subtract the volume of fat from the total volume of the breast to provide the volume of fibroglandular tissue.
Volpara’s unique approach to determining a unique value for fat in the individual breast makes its volumetric assessment very robust for clinical and research applications. The Volpara breast density will remain constant regardless of the mammographic imaging equipment allowing values from one year to be compared with other years, and values between populations to be compared one to the other as well as temporally.
Robustness provides quantitative reliability, allowing Volpara to be incorporated in both research and imaging protocols. Imaging protocols are becoming increasingly important as adjuvant imaging is being added to traditional screening mammography.
Examples of Volpara volumetric breast density as compared to BI-RADS density assessment are shown here:
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