Obese women have 'stiffer' breast tissue, increasing breast cancer risk

Obesity is a risk factor for breast cancer, but it’s not clear why. Researchers have now found that obesity involves changes that stiffen breast tissue, which in turn promotes tumor development.

The discovery also led researchers to conclude that using adipose tissue and cells from obese patients for breast reconstruction surgery may actually plant the seed for cancer to recur, according to the study published August 19, 2015 in Science Translational Medicine.

“We all know that obesity is bad. The metabolism changes and hormones change, so when looking for links to breast cancer, researchers almost exclusively have focused on the biochemical changes happening,” said senior author Claudia Fischbach-Teschl, PhD, MS, Associate Professor of Biomedical Engineering at Cornell University in Ithaca, NY. “But what these findings show is that there are also biophysical changes that are important.”

In this study, the researchers first examined female mice and found that obesity induces fibrotic remodeling of the mammary fat pad, which leads to changes in extracellular matrix (ECM), the material that surrounds fat cells in the breast. That is, the obese mice had stiffer ECMs in the absence of tumors. The researchers also examined tumor-free human breast tissues from obese women and normal-weight women, and found the same type of stiffness in the ECMs of obese women. The researchers determined that these biomechanical changes were induced by excess myofibroblasts and adipose stem cells (ASCs).

Next, the researchers took human breast cancer cells and planted them on the ECMs from obese mice and from normal-weight mice. They found that the ECMs from obese mice had more cancer cell growth, as well as the growth of premalignant breast cells.

Although obese women are encouraged to get regular mammograms, these biomechanical signs of disease won’t often appear because fat cells can obscure dense fibrosis on conventional imaging. The findings “may inspire use of higher resolution imaging techniques to detect those changes,” Dr. Fischbach-Teschl said. “Right now, people don’t look for [stiffer extracellular matrices] as a clinical biomarker.”

In terms of potentially putting this research into clinical practice, the investigators found good news and bad news.

The good news: When the researchers put obese mice on a restricted calorie diet, they found that fibrosis in their mammary fat decreased, which suggests a possible therapy for obesity-related cancers.

The bad news: When performing breast reconstructive surgery in patients after mastectomy, the use of adipose tissue and cells from obese individuals may have the capacity to promote breast cancer recurrence.

“What our data suggests is that it is really important where these cells are being taken from,” Dr. Fischbach-Teschl said. “If you use these cells from an obese patient, they are very different and you may actually be driving malignancies if you implant them.”