Women Living Near Federally Designated Toxic Superfund Sites Face Higher Risk of Developing Aggressive Breast Cancer

Despite progress made in diagnosing and treating breast cancer, this disease remains of the most common malignancies affecting women worldwide. According to data from the American Cancer Society (ACS), breast cancer also represents a major portion of cancer-related morbidity and mortality among women diagnosed this form of cancer.[1]

Results from a study by a team of researchers at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine suggests that women living close to federally designated Superfund sites are more likely to develop aggressive breast cancers — including treat triple-negative breast cancer (TNBC), a hard to treat sub type of breast cancer that that is recognized as for its aggressive behavior and poor prognosis.* This sub type of breast cancer is also known for overall poorer survival when compared to ER/PR-positive or HER2-positive breast cancers.[2] In addition, the heterogeneity of TNBC, with varying molecular sub-types influencing prognosis, treatment options** and response, further contributes to the complexity of the disease.

Superfund sites
According to a study by the National Institutes of Health (NIH), 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 (EPA) as needing cleanup because it poses a risk to human health or the environment. [3] In 1980, the US Congress established a federal environmental remediation program known as the Comprehensive Environmental Response, Compensation, and Liability Act of 1980 (CERCLA) which identifies and pays for the cleanup for these Superfund sites.[4] Today, the EPA has identified more than 1,700 sites. 

Environmental factors
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,” noted 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 explained.

“Although health and Superfund sites have been studied for decades, ties between environmental degradation and pollution and breast cancer remain under-researched, Kobetz added.

This let her to  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%. [5]

The researchers then turned to specifically study TNBC and found that living in proximity to a Superfund site is also associated with increased risk for this aggressive sub-type 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. [6]

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,” Kobetz noted. “We need to better appreciate how environmental conditions may be driving variability in cancer outcomes,” she added.

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 explained, adding “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.[7]

“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,” she concluded.

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Note: * The American Society of Clinical Oncology and College of American Pathologists guidelines define Triple Negative Breast Cancer (TNBC), which represent approximately 10–15% of all diagnosed breast cancers, as a cancer where estrogen receptor (ER) and progesterone receptor (PR) are less than 1% by immunohistochemistry (IHC), and human epidermal growth factor receptor 2 (HER2) is either 0 to 1+ by IHC, or IHC 2+ with negative fluorescence in situ hybridization (FISH).

** In treating TNBC, therapies directed to specific molecular targets have rarely achieved clinically meaningful improvements and outcomes with chemotherapy remaining an important treatment modality. However, over the last 2 decades, a better understanding of TNBC’s unique biology have resulted on the development of promising treatment strategies. For example, molecular profiling has revealed distinct sub-types within TNBC. This understanding resulted in the developing of targeted therapies and immunotherapies that have emerged a possible practice-changing treatments, offering new hope for patients diagnosed with TNBC.[8]

Reference
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[2] Li X, Yang J, Peng L, Sahin AA, Huo L, Ward KC, O’Regan R, Torres MA, Meisel JL. Triple-negative breast cancer has worse overall survival and cause-specific survival than non-triple-negative breast cancer. Breast Cancer Res Treat. 2017 Jan;161(2):279-287. doi: 10.1007/s10549-016-4059-6. Epub 2016 Nov 25. PMID: 27888421.
[3] Agelidis A, Ter-Zakarian A, Jaloudi M. Triple-Negative Breast Cancer on the Rise: Breakthroughs and Beyond. Breast Cancer (Dove Med Press). 2025 Jun 26;17:523-529. doi: 10.2147/BCTT.S516125. PMID: 40599557; PMCID: PMC12209529.
[4] United States. Comprehensive Environmental Response, Compensation, and Liability Act of 1980. Pub. L. 96–510, approved December 11, 1980. 42 U.S.C. § 9601
[5] Borowsky PA, Nahodyl L, Herbach E, Lee M, Elliott NS, Telonis AG, Goel N, Kobetz EN. Residential proximity to national priorities list superfund sites is associated with increased likelihood of metastatic breast cancer presentation. Sci Rep. 2025 Jul 2;15(1):23256. doi: 10.1038/s41598-025-05722-6. PMID: 40603361; PMCID: PMC12222789.
[6] Borowsky PA, Nahodyl L, Sable S, Sierra MA, Gonzalez S, Herbach EL, Elliott NS, Telonis AG, Goel N, Kobetz EN. Residential Proximity to NPL Superfund Sites and High Particulate Matter Exposure is Associated with Increased Likelihood of Triple Negative Breast Cancer. Cancer Epidemiol Biomarkers Prev. 2025 Aug 11. doi: 10.1158/1055-9965.EPI-25-0677. Epub ahead of print. PMID: 40788043.
[7] Telonis AG, Hernandez AE, Borowsky PA, Reguero Hernandez ED, Lyon PD, Cimmino L, Garcia-Martinez L, Zha M, Morey L, Net J, Yepes M, Collado-Mesa F, Boone M, Merchant NB, Kobetz EN, Kesmodel SB, Figueroa ME, Goel N. Molecular Portraits of Social Adversity in Breast Cancer: Neighborhood Disadvantage is Associated with Epigenetic Deregulation of Key Oncogenic Pathways. Cancer Epidemiol Biomarkers Prev. 2025 Aug 14. doi: 10.1158/1055-9965.EPI-25-0123. Epub ahead of print. PMID: 40810618.
[8] Bianchini G, De Angelis C, Licata L, Gianni L. Treatment landscape of triple-negative breast cancer – expanded options, evolving needs. Nat Rev Clin Oncol. 2022 Feb;19(2):91-113. doi: 10.1038/s41571-021-00565-2. Epub 2021 Nov 9. PMID: 34754128.

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