Women with higher blood levels of two common “forever chemicals” may face an increased risk of developing a particularly aggressive form of breast cancer, according to a new study from the National Institutes of Health (NIH), part of the U.S. Department of Health and Human Services (HHS).
The study identified a link between estrogen receptor-negative, or ER-negative, breast cancer and two widely encountered chemicals: perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS). Women with higher concentrations of these substances in their blood were more likely to develop this type of cancer. However, researchers found no clear link between either chemical and overall breast cancer risk.
Both substances belong to a large family of per- and polyfluoroalkyl substances, commonly known as PFAS. These chemicals have been used in many everyday consumer products and are often described as “forever chemicals” because they are resistant to degradation in the environment. They can also accumulate in the human body and stay there for years.
“Women deserve clear answers about how chemicals in their environment can affect their health,” said HHS Secretary Robert F. Kennedy, Jr. “This NIH study links two permanent chemicals to a higher risk of ER-negative breast cancer and demands further investigation. Under President Trump’s leadership, we will pursue the evidence, confront environmental health risks, and give women the information they need to protect their health.”
Why this aggressive breast cancer is concerning
ER-negative breast cancer differs from more common forms of the disease because its tumor cells lack the receptors that allow estrogen to stimulate cancer growth. These cancers are often more aggressive and generally have poorer outcomes than tumors that respond to estrogen.
Despite their seriousness, researchers still have relatively little information about what makes a person more likely to develop ER-negative breast cancer. The new findings suggest that exposure to certain persistent environmental chemicals may be a contributing factor.
“Our findings, which we confirmed using a meta-analysis of previous research, indicate that some existing PFAS, including PFOA and PFOS, are associated with a higher risk of ER-negative breast cancer, a more aggressive tumor type with few known risk factors,” explained Alexandra White, Ph.D., a researcher at NIH Stadtman, who led the study.
The results were published in the Journal of Clinical Oncology.
Ever-higher levels of chemicals linked to greater cancer risk
To study the possible link, NIH scientists and their collaborators examined blood samples collected years before the participants were diagnosed with cancer. The researchers measured the concentrations of 17 different PFAS chemicals, allowing them to compare past exposure levels with later breast cancer outcomes.
The results revealed substantial differences for two chemicals. Women in the highest PFOA exposure group had a 67% higher rate of ER-negative breast cancer than women in the lowest group. The association was even stronger for PFOS, with the highest exposure group showing a 93% higher rate, almost twice that of the lowest group.
These percentages represent relative differences between groups rather than the absolute probability that a woman will develop breast cancer. The results also establish an association, but do not prove that the chemicals directly cause the disease.
The analysis used data from the Sister Study, a major research project led by the NIH’s National Institute of Environmental Health Sciences (NIEHS). Between 2003 and 2009, the study included 50,884 women aged 35 to 74 in the United States and Puerto Rico.
Not all participants had breast cancer when they enrolled, although each had a full or half-sister who had already been diagnosed with the disease. For the PFAS survey, researchers analyzed information from 1,609 women who later developed breast cancer and a control group of 2,269 women.
Could reducing exposure to PFAS reduce cancer risk?
Although PFAS can remain in the environment and in the body for long periods of time, researchers emphasize that exposure is not necessarily inevitable. The findings could potentially help identify new ways to reduce the risk of aggressive breast cancer.
“These findings are important for women’s health in general,” said first author Che-Jung Chang, Ph.D., who previously worked as a researcher at the NIH and is now a researcher at DLH, a scientific research organization. “Although PFAS are persistent in the environment and in our bodies, their exposure is still potentially modifiable, meaning people can take steps to reduce their exposure, and these findings could open new avenues for prevention.”
Researchers also want to understand how these chemicals might influence the development of cancer. Because the strongest associations appeared in tumors lacking estrogen receptors, the results suggest that PFAS may act through biological processes unrelated to hormone signaling.
Potential explanations include changes in gene activity or alterations in the immune system. However, the study did not directly investigate these mechanisms, so their involvement remains unclear.
New Forever Chemicals products raise unanswered questions
Although PFOA and PFOS have been largely eliminated and replaced with other PFAS compounds, measurable amounts of both substances are still present in most people’s bodies. Their persistence means that exposure to these older chemicals remains a potential public health problem.
Researchers say additional research should focus on populations most exposed to PFAS, as well as groups that experience higher rates of ER-negative breast cancer. Such research could help clarify the strength of observed associations and determine whether certain populations face higher risks.
Scientists also need to determine whether new chemicals introduced to replace PFOA and PFOS raise similar health concerns.
“More research is needed, particularly to assess the breast cancer risk associated with new replacement PFAS chemicals,” White said.
The findings add to growing questions about the long-term health effects of perennial chemicals and highlight the importance of understanding how environmental exposures may contribute to aggressive forms of breast cancer.
The research was supported by NIEHS grants Z01ES044005; Z1AES103332; and R01ES032831.
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