Study Finds Forever Chemicals May Make Breast Cancer Cells More Aggressive
Ryan Lidgett, a Ph.D. student in chemistry at UNC and the study’s lead author, was part of a team of researchers that discovered that long-term exposure to two PFAS chemicals can change the way breast cancer cells behave.
June 23, 2025 I By Dave DeFusco
They’re in your frying pan, your raincoat, your takeout box—and your blood. Known as “forever chemicals,” PFAS—per- and polyfluoroalkyl substances—are synthetic pollutants so stubborn they don’t break down for years, building up silently in our bodies and the environment with every meal, spill and wash.
Now, a team of UNC-Chapel Hill researchers show in a new study, “An Analytical Screening Platform to Differentiate Acute and Prolonged Exposures of Per- and Polyfluoroalkyl Substances on Invasive Cellular Phenotypes,” that certain PFAS may do more than just hang around. They might also make some breast cancers more aggressive over time.
“What we found is that long-term exposure to these two PFAS chemicals can change the way breast cancer cells behave,” said Ryan Lidgett, a Ph.D. student in chemistry at UNC and the study’s lead author. “They become more invasive, which is a major warning sign for cancer getting worse.”
The study, published in the Journal Toxicological Sciences, is the first to use a new kind of screening system that mimics how cancer cells move in the body. It lets scientists see how cells respond differently to short- and long-term exposures to PFAS. The results could help public health officials better understand the risks we face and why we should care about these invisible pollutants.
PFAS are a family of thousands of chemicals used for decades to make water, grease and heat-resistant products. Because they are nearly impossible to break down, they build up over time in the environment and our blood. The CDC estimates that nearly 97% of Americans have PFAS in their bodies.
Worse still, some of these chemicals, especially older “legacy compounds” like PFOA and PFOS, are linked to liver damage, diabetes, weakened immune systems and cancer, including breast cancer. In 2023, the National Cancer Institute officially labeled PFOA as a human carcinogen.
Breast cancer is the second-leading cause of cancer deaths among women in the United States. About 1 in 8 women will be diagnosed in their lifetime. Two-thirds of those cases are hormone-sensitive, meaning they respond to estrogen and other hormones. Earlier studies hinted that PFAS could increase the risk of breast cancer, especially among women after menopause. But until now, most labs have focused on the outcomes of short chemical exposure, typically just hours or days. Real life doesn’t work that way.
“People aren’t exposed to PFAS for just a few days,” said Dr. Matthew Lockett, senior author of the paper and an associate professor of chemistry. “These chemicals have long half-lives in your circulatory system; a single exposure can take years to clear the body. We wanted to see what happens when cells are exposed for weeks, not just hours, to mimic the exposures many individuals encounter.”
The UNC team built a new type of screening platform using paper-based scaffolds. Think of these paper sheets like scaffolding at a construction site but instead of holding up buildings, they hold up tiny blobs of gel filled with cancer cells. The cells are then placed in a dish with PFAS-spiked liquid and left to grow. Over time, the scientists measured how many of those cells migrated out of the paper and into the dish, a sign that they were becoming more invasive.
“The invasive cells are like dandelions in your yard,” said Lidgett. “The cells are readily identified, and if more are present, it indicates the cancer can spread more easily.”
The team, which included researchers from the UNC Department of Physics and Astronomy, Lineberger Comprehensive Cancer Center, and Biomedical Research Imaging Center, tested two well-known PFAS—PFOA and PFOS—on two types of human breast cancer cells: MCF7, which are hormone-sensitive like many breast cancers, and MDA-MB-231, which are triple-negative, a more aggressive type that doesn’t respond to hormone therapies. Then, they exposed the cells in two ways: an acute or one-time exposure lasting less than 48 hours and a prolonged exposure in which the cells were maintained in a constant concentration of PFOA, PFOS or a mixture of the two for several weeks.
Here’s what they discovered:
- Short-term exposure didn’t lead to much change in the motility or invasiveness of the cancer cells.
- Long-term exposure caused both types of cancer cells to become significantly more invasive, especially at higher concentrations of PFOA and PFOS.
- Even at concentrations found in people’s blood in polluted areas like Wilmington, North Carolina, the cancer cells showed signs of adapting over time through altered growth rates.
“These are subtle but meaningful changes,” said Lidgett. “You might not see them after a day or two, but weeks of exposure start to reveal a more dangerous pattern.”
While many toxicology tests focus on immediate effects, this research shows that slow, ongoing exposure to PFAS can have delayed consequences, particularly for diseases like cancer, which can take years to develop.
“This shows we need to rethink how we test chemicals for safety,” said Dr. Lockett. “The kind of slow, low-level exposure people get from drinking water or everyday products may be more harmful than we thought, especially over time.”
Their platform could become a faster, cheaper and more accurate way to screen not just PFAS, but other chemicals that might quietly reshape how our cells behave. Although “legacy” PFAS chemicals have already been largely phased out in the United States, they persist in the environment. Thousands of newer PFAS are in use today, many of which haven’t been properly studied. For now, the researchers hope their work sparks a broader conversation about chemical safety and public health.
“We’re not just talking about cells in a dish,” said Lockett. “We’re talking about how the environment we live in—our air, water, food—can affect real people, in real ways, over time.”