One Step Closer to a Promising Breast Cancer Prevention Strategy

Wednesday, November 10, 2021

A non-steroidal anti-inflammatory drug lowers breast density, a risk factor for breast cancer, according to new study from University of Arizona Health Sciences researchers.

Researchers at the University of Arizona Health Sciences and Stony Brook University have provided the first clinical evidence that a non-steroidal anti-inflammatory (NSAID) may lower the risk of breast cancer and recurrence.

“We wanted to see if there are ways to decrease fibrosis, inflammation and other breast cancer markers to lower the risk of cancer actually happening in the first place, and to prevent existing cancer from growing and spreading,” said Pavani Chalasani, MD, MPH, associate professor of medicine at the UArizona Cancer Center and principal investigator of the Arizona study site.

The results were published in the journal Clinical Cancer Research. Around 50 postmenopausal women at the University of Arizona or Stony Brook Cancer Center agreed to take the NSAID sulindac for 12 months in addition to their standard aromatase therapy. Breast density was measured by magnetic resonance imaging (MRI) and was compared to that of a similar group of women taking aromatase inhibitors, but not sulindac.

For most breast cancers, growth is driven by the hormone estrogen. Following surgery, women with early-stage estrogen receptor (ER+) breast cancer often receive hormone therapy called aromatase inhibitors that block the body from making estrogen. Despite this, the cancer will return in around 1 in 5 women with ER+ disease.

Denser, more fibrous breasts are a known risk factor for breast cancer and are screened through mammograms. Back in 2012, researchers at the University of Arizona received a National Cancer Institute grant to test whether the NSAID sulindac could lower breast density when added to hormone therapy. The study took place at the University of Arizona and Stony Brook Cancer Centers.

At one year, women taking sulindac had lower breast density than at the start of the study. In contrast, there was no significant change in the group of women not taking sulindac.

“This study was exciting because sulindac reduced breast density, which we believe correlates with a lower risk of breast cancer,” said Jessica A Martinez, PhD, assistant research professor in the UArizona Department of Nutritional Sciences and Wellness and Cancer Center associate.

Additionally, aromatase inhibitors often lead to muscle and joint pain, so the researchers looked at whether sulindac helped to reduce pain and improve quality of life. These results will be published at a later date. Building on the results, the UArizona Cancer Center researchers are studying the physical and molecular changes that lead to muscle and joint pain after starting an aromatase inhibitor. Their goal is to identify biomarkers that could guide treatment decisions.

“Sulindac is generally regarded as safe but there are some side effects associated with NSAIDs, so you don't want to just start everyone on it,” said Dr. Martinez. “You want to make sure you're targeting treatment to the people who need it.”

NSAIDs target a pathway in cells that make pro-inflammatory molecules such as prostaglandins. Since inflammation is strongly implicated in cancer, scientists have studied NSAIDs as a possible means of preventing cancer. However, strong evidence from human studies was lacking.

The researchers chose to test sulindac over more common NSAIDs such as ibuprofen. Ibuprofen targets one step in the inflammation pathway while sulindac is non-selective, inhibiting multiple parts of the pathway, as well as possibly having other anti-tumor effects. In preclinical models, NSAIDs reduce mammary tumor growth as well as aromatase levels.

This was the first study to show that sulindac reduces breast density in women, but the authors caution that it is too early to say sulindac definitively lowers the chances of breast cancer. Additional studies are needed to confirm this finding, but this is the first step forward.

“Through research into new approaches we hope to one day prevent detrimental effects from cancer  therapies” Dr. Chalasani said.

Media contact:
Megan Guthrie