Researchers Identify Specific Associations Between Cancer Risk and Breast Density

Previous research indicates that dense breast tissue is a risk factor for breast cancer development. Some studies have suggested that women who have highly dense breasts (≥60%-75% dense tissue) were as much as six times more likely to develop carcinoma of the breast than women whose breasts consisted primarily of fatty tissue.

A group of researchers from the Mayo Clinic evaluated samples of breast tissue from 60 women age 40-85 years (mean age, 50.1 years) who volunteered for the study. Inclusion criteria included no symptoms of breast cancer, a normal mammogram within six months of study onset, and no personal history of breast cancer. Women were excluded if they had breast-related symptoms or bleeding tendencies, or if they were receiving endocrine therapy.

Using ultrasonography-guided core-needle biopsy, investigators obtained tissue samples from both dense and non-dense areas of the breast from each participant. Next, they determined the percentage of epithelium tissue, stroma (connective tissue), and fat content in each sample. The authors said their study was the first to analyze both types of tissue taken from the same breast. Karthik Ghosh, MD, breast cancer researcher and physician with the Mayo Clinic, led the research team. Dr. Ghosh said they “found a dramatic difference in tissue composition between dense and non-dense tissue in the breast.”

Consistent with earlier studies, the preliminary results from 34 patients showed that dense tissue contained much higher concentrations of epithelium and stroma but less fat than tissue samples obtained from less-dense areas of the breast.

Area Sampled Epithelium, % Stroma, % Fat, %

Dense 6 64 30

Non-dense 1 20 80

“This shows us that both the epithelium and stroma contribute to density and suggests that the large difference in stroma content in dense breast tissue may play a significant role in breast cancer risk,” Dr. Ghosh explained.

Researchers also noted greater evidence of lobular involution in the non-dense tissue. Lobular involution refers to a decrease in the size and number of milk ducts. This lobular regression typically accelerates with age and is associated with a reduced risk of breast cancer. Investigators found “no involution” in 24% of the dense tissue samples versus 8.8% in non-dense tissue samples; they found “complete involution” in 82.5% of the non-dense samples compared with 35.2% of the dense samples. The authors concluded that their study documents a “dramatic difference in tissue composition” between these two types of breast tissue.

A second team of researchers at the Mayo Clinic, led by Celine Vachon, PhD, analyzed the biopsy samples for aromatase expression. They found a greater concentration of aromatase and increased intensity of expression in the stromal cells of dense tissues samples compared with non-dense samples. Aromatase enzyme is integral to the conversion of androgen into estrogen, a hormone highly implicated in breast cancer development. Dr. Vachon believes that her group’s findings may help explain why women whose breasts have a higher ratio of dense tissue to fatty tissue are at greater risk for breast cancer.