Living near Superfund sites increases risk of aggressive breast cancer

Women living close to federally designated Superfund sites are more likely to develop aggressive breast cancers - including the hard-to-treat triple-negative subtype - according to new studies from Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine.

According to a National Institutes of Health study, some especially aggressive forms of breast cancer that are resistant to treatment are on the rise. Now, three recent studies by Sylvester researchers have uncovered links between breast cancer, Superfund sites and social adversity. A Superfund site is a location that has been contaminated by hazardous waste and identified by the Environmental Protection Agency as needing cleanup because it poses a risk to human health or the environment.

The rise in breast cancer cases - particularly aggressive, hard-to-treat types such as triple-negative breast cancer - highlights the need to examine potential environmental factors contributing to these trends. In Florida, the presence of 52 active Superfund sites has become a focus, prompting members of Sylvester's Community Advisory Committee to raise awareness and connect with the cancer center about these issues.

"Members of our community raised concerns that where they lived was making people sick," said Erin Kobetz, Ph.D., M.P.H., an epidemiologist and associate director for community outreach and engagement at Sylvester and Judy H. Schulte Senior Endowed Chair in Cancer Research.

"Overwhelmingly, the people who were speaking up about this lived in a neighborhood relatively close to a Superfund site. There's a growing body of evidence that living in neighborhoods close to these sites is associated with poor health outcomes," she added.

Although health and Superfund sites have been studied for decades, ties between environmental degradation and pollution and breast cancer remain under-researched, Kobetz said. So, she set up a multidisciplinary team of physicians, basic scientists and epidemiologists to dive in and study breast cancer and proximity to Superfund sites in Florida. Using Sylvester's SCAN360 data portal, her team was able to retrieve very granular data of South Florida's neighborhood characteristics and cancer risks.

Proximity to Superfund sites

The first study examined more than 21,000 cases of breast cancer in Florida diagnosed from 2015 to 2019. Kobetz and her co-authors wondered whether proximity to a Superfund site was related to whether breast cancer was metastatic. The researchers found that living in the same census tract as at least one Superfund site raised the likelihood of metastasized breast cancer by about 30%.

The researchers then turned to specifically study triple-negative breast cancer (TNBC) and found that living in proximity to a Superfund site is also associated with increased risk for this aggressive subtype of breast cancer. Kobetz and her colleagues wanted to further explore the ties between TNBC and a certain pollutant, particulate matter 2.5 (PM2.5), which is a pollutant smaller than 2.5 microns. They report that higher exposure to PM2.5 leads to higher risk of TNBC in South Florida.

The two studies were published in Scientific Reports and Cancer Epidemiology Biomarkers and Prevention. Together, they highlight the risk that simply living close to a Superfund site may pose in terms of breast cancer.

These studies, as well as federal funding priorities, give an increasing emphasis on the role of the environment in health outcomes. We need to better appreciate how environmental conditions may be driving variability in cancer outcomes."

 Erin Kobetz, Ph.D., M.P.H., epidemiologist and associate director for community outreach and engagement at Sylvester and Judy H. Schulte Senior Endowed Chair in Cancer Research

Biomarkers in tumors

Clinicians and researchers are concerned about environmental factors in a patient's health journey, but there's still a lot to learn about how those factors may be influencing diseases at the molecular level.

That's why Aristeidis Telonis, Ph.D., a research assistant professor of biochemistry and molecular biology at the Miller School, wanted to dig into what might leave a chemical fingerprint in patients, a biomarker or even shape the progression of cancer.

The team, co-led by Kobetz, analyzed breast cancer samples from 80 patients in the Miami area. They went deeper than merely genetic testing of the DNA; they also checked the instruction notes (epigenome) and the real-time messages (RNA) that show how the DNA is being put into action.

The researchers then compared the genetic biomarkers to a composite measure of neighborhood context, and elements known to influence health outcomes. They observed that patients from neighborhoods with fewer health-promoting resources were more likely to exhibit these biomarkers and experience more aggressive forms of breast cancer.

"This deprivation index is very strongly associated with more aggressive breast cancers," Telonis said. "It's a simple, but very important correlation." The study is published in Cancer Epidemiology Biomarkers and Prevention and is among the first to do a deep dive into these associations with molecular events inside a tumor, he said. The findings open the door to highly personalized care, with treatment plans that can best address the specific tumor conditions that a patient presents.

"The goal is that when a patient comes in, the doctor not only assesses the tumor characteristics, but also considers the patient's resources and what that may mean molecularly," Telonis said. "Eventually, that should help inform treatment."

Community first for a healthy future

Kobetz stressed that this work was in direct response to the community's concerns.

"We have a signal, and we're compelled and encouraged by our Community Advisory Committee to pursue it," Kobetz said. "The community had a perspective, and now we have empirical and scientific data to suggest that their concerns may be valid. These studies are the first puzzle pieces that will help us figure out what we should be focusing on next."