High mammographic density (MD) is among the strongest markers of breast cancer risk. MD is routinely assessed using the Breast Imaging- Reporting and Data System (BI-RADS) categories (1: almost or entirely fat; 2: scattered density; 3: heterogeneously dense; 4: extremely dense). Women whose mammogram is rated as BI-RADS category 4 are at approximately 4-fold risk of breast cancer compared to women with BI-RADS category 1. MD is generally believed to be largely determined by the interplay of hormones and genetic factors. However, although it shares risks factors with breast cancer, the etiology of mammographic breast density—particularly the role of environmental exposures—remains poorly understood. Furthermore, whether breast cancer risk factors act through elevated breast density continues to be controversial.
Cadmium is a persistent heavy metal pollutant found in grains, vegetables, and legumes, as well as tobacco; thus, chronic environmental exposure at low levels is widespread in the general population. Environmental exposure to cadmium has recently been associated with breast cancer in two epidemiological studies. The carcinogenicity of cadmium in breast tissue might be due to cadmium’s action as an endocrine disruptor, or “xeno-estrogen,” as has been observed in laboratory experiments. However, the underlying mechanisms through which cadmium acts on breast tissue remain unclear.
We hypothesize that cadmium increases MD, and that this could explain part of cadmium’s potential association with breast cancer risk. In this study, we will recruit 1,000 women and estimate the association between urine cadmium, an established marker of environmental cadmium exposure, and MD. We will also explore the cadmium-breast density association among subgroups of women; if cadmium acts as a “xeno-estrogen”, we expect its association with breast density to be strongest in postmenopausal women and women who have never used hormone replacement therapy. In addition we will follow up on our preliminary evidence that cadmium is most strongly associated with increased MD among nulliparous women and smokers.
This study at the University of Wisconsin Carbone Cancer Center in Madison and the Fred Hutchinson Research Center in Seattle, Washington, is investigating whether cadmium, a heavy metal found in the environment, is related to breast density. The researchers will measure the amount of cadmium and other heavy metals found in participants' urine samples. They will also review the participants' recent mammography reports to collect data on breast density. The researchers wanted to enroll up to 1,000 volunteers. The Call to Action for this study was sent to Army of Women members on December 5, 2012. The researchers were able to close enrollment less than 26 hours later, on December 6, 2012, after the Army of Women provided them with 2,580 women who were interested in enrolling in the study.