Questions the Study Will Address
What are the questions we are hoping to answer with this study?
We are examining ways to expand the utility of the mammogram beyond only screening for the presence of cancer. In particular, we are examining features on the mammogram that might help identify groups of women who are at higher or lower risk of developing breast cancer in years following the mammogram. The features of interest reflect the variations in the amount and location of dense vs. fatty breast tissue, viewed as variations in the light and dark regions on the mammogram image. Below, we describe the different features of the mammogram image that we will study over the next five years.
Dense area and percent density
Fatty breast tissue is radiologically more translucent than dense, or fibroglandular, breast tissue. This means that regions of a breast that are comprised of fatty tissue will be darker on a mammogram image than regions that are comprised mainly of dense tissue. Therefore, mammograms of primarily fatty breasts will appear darker than mammograms of primarily dense breasts. The two figures below illustrate mammograms of breasts with very different amounts of dense tissue on the image. The mammogram on the left is of a primarily fatty breast, and the mammogram on the right is of a primarily dense breast. The fatty breast appears quite dark relative to the dense breast since it is the dense tissue that results in the light or white regions on the mammogram.
The two quantities that are commonly used to describe the differences in the amount of dense tissue in a breast, as reflected on a mammogram, are dense area, or the absolute area on the mammogram that is bright enough to be considered dense tissue, and percent density, the percent area of the breast image on the mammogram that is bright or white and considered dense tissue.
In our study, we will estimate both dense area and percent density using a computer program, which is illustrated below. The use of this computerized method requires a trained technician to set two values. The first of these defines the region on the mammogram image that corresponds to the breast. The second defines the brightness level in the mammogram image that corresponds to the dense tissue in the breast. We hypothesize that for the same age and weight, women with increased percent density and increased dense area have a higher risk of developing breast cancer.
Distribution or patterns of density
The simple amount or percent of dense tissue on a mammogram may not tell the entire story. Two breasts can have the same percent density, but the dense tissue can be distributed in different patterns throughout the breast. For example, the breasts imaged in the two mammograms pictured below have the same percentage of dense tissue. However, the mammogram on the left shows one central area or cluster of dense tissue, while the mammogram on the right shows many smaller regions of dense tissue scattered throughout the breast. We will investigate whether the different patterns of dense tissue in a breast, such as illustrated below, are associated with differences in the risk of developing breast cancer.
As you know, the mammogram is a 2-dimensional image. Therefore, a mammogram image is not a perfect illustration of the total amount of dense breast tissue. Looking at the image below, you see that not all of the areas with dense breast tissue that are highlighted on the mammogram have the same brightness. Some areas of dense tissue appear whiter than other areas. One reason for this is that the dense tissue is not of the same thickness at all points throughout the breast. As an example, think of a marble and a glass disc of similar size, placed side by side at some position when a breast is imaged in a mammogram. The marble and glass disc will be of very similar shape (a circle) and size on the mammogram. However, the marble will be brighter than the glass wafer, since it has a greater volume.
With a mammogram, it is only possible to estimate two-dimensional areas of dense tissues in the breast. However, the actual three-dimensional volume of dense breast tissue is the quantity that is likely to be important. In this study, using a standard included on each mammogram, we will be able to estimate the actual volume of dense tissue in the imaged breast. We will then investigate whether volumetric density is associated with the risk of developing breast cancer.
Changes in density due to HRT
Two questions in our study address whether changes in a woman's percent density are important in breast cancer. The first question examines whether the changes in percent density over a woman's life are associated with the risk of developing breast cancer.
Pictured below is a series of mammograms taken from the same woman over the course of 10 years. Notice how there are differences in the amount and proportion of white tissue over time. We will examine whether these types of changes in breast density are associated with the risk of developing breast cancer.
The second question looks specifically at changes in percent density induced by hormone replacement therapy (HRT). The goal is to determine if these HRT induced changes are associated with the risk of developing breast cancer.
Pictured below is an example of a change that can occur in some women when they use HRT. The set of mammograms on the left is from a woman before she began taking HRT. The mammograms on the right were taken from the same woman one year after she started to use HRT. This woman experienced a dramatic increase in breast density that corresponded to her HRT use. In this study, we are asking whether these changes in breast density, as measured on a mammogram, can help us identify women whose risk of developing breast cancer increases in response to taking HRT. We think that women who experience a dramatic increase in breast density as a response to HRT use are at a greater risk for breast cancer than women who do not experience such an increase.
We are interested in obtaining information from women who are currently on HRT, as well as from those who have stopped their HRT use. Using this information, we hope to provide current and past users a clearer estimate of the risk of developing breast cancer that corresponds to their use of HRT.
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