Women with higher blood concentrations of two widely used industrial chemicals may face an increased risk of developing an aggressive form of breast cancer, according to a new study by the US National Institutes of Health (NIH). The research identified an association between per- and polyfluoroalkyl substances (PFAS), specifically PFOA and PFOS, and estrogen receptor-negative (ER-negative) breast cancer.
Published in the Journal of Clinical Oncology, the study found no clear association between these chemicals and breast cancer risk overall. However, women with higher levels of the two substances had higher rates of ER-negative breast cancer, a subtype associated with more aggressive disease and fewer established risk factors.
PFOA and PFOS Associated With Higher Rates of ER-Negative Breast Cancer
PFAS are a large group of chemicals used in various consumer and industrial products. Commonly called “forever chemicals”, they break down very slowly in the environment and can remain in the human body for years.
The NIH research found that higher blood plasma concentrations of two legacy PFAS compounds, perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), were associated with increased rates of ER-negative breast cancer.
Researchers reported that women in the group with the highest PFOA concentrations had a 67% higher rate of ER-negative breast cancer than those with the lowest levels. For PFOS, the rate was 93% higher, representing nearly twice the rate observed in the lowest-exposure group. These figures describe relative differences between groups rather than an individual’s absolute probability of developing breast cancer.
ER-negative tumours lack estrogen receptors, meaning the hormone cannot promote cancer cell growth through those receptors. Compared with hormone receptor-positive breast cancers, ER-negative tumours tend to be more aggressive and are associated with poorer outcomes.
“Our findings, which we confirmed using a meta-analysis of prior research, indicate that certain legacy 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 NIH Stadtman Investigator Alexandra White, Ph.D., who led the study.
Researchers Analyse Blood Samples From More Than 3,800 Women
The research team measured 17 different PFAS compounds in blood samples collected years before the participants received a breast cancer diagnosis. The analysis drew on data from the Sister Study, a long-term research project conducted by NIH’s National Institute of Environmental Health Sciences (NIEHS).
The Sister Study enrolled 50,884 women aged 35 to 74 across the United States and Puerto Rico between 2003 and 2009. None had breast cancer when they joined, although all had a full or half-sister who had previously been diagnosed with the disease.
For the PFAS analysis, researchers examined 1,609 women who subsequently developed breast cancer and compared their results with those of 2,269 women who did not develop the disease.
The study’s findings add to growing evidence that environmental exposures may influence women’s health and contribute to differences in breast cancer risk.
“These findings matter for women’s health broadly,” said first author Che-Jung Chang, Ph.D., a former research fellow at NIH and a current researcher at DLH, a scientific research organization. “Although PFAS are persistent in the environment and in our bodies, exposure to them is still potentially modifiable, meaning people can take steps to reduce their exposure, and these findings could open new avenues for prevention.”
More Research Needed Into PFAS Exposure and Cancer Risk
The researchers suggested that PFAS may influence ER-negative breast cancer through biological mechanisms unrelated to hormone receptors. Potential explanations include changes in gene activity or immune system function. However, the study did not directly investigate these mechanisms, and further research is needed to establish how the chemicals may affect cancer development.
The findings also raise questions about newer PFAS compounds. Although PFOA and PFOS have been largely phased out and replaced by other PFAS chemicals, exposure to these substances remains widespread because of their persistence in the environment and the human body.
“More research is needed, particularly evaluating the risk of breast cancer associated with newer replacement PFAS chemicals,” White said.
The researchers recommend further investigation involving populations with higher PFAS exposure and groups more affected by ER-negative breast cancer. The study establishes an association, not proof that exposure to PFOA or PFOS directly causes breast cancer.
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