Two 'forever chemicals' associated with higher risk of aggressive breast cancer in analysis

by National Institutes of Health

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Women with higher blood levels of two common per- and polyfluoroalkyl substances, also familiarly known as PFAS, were more likely to develop estrogen receptor-negative, or ER-negative, breast cancer, according to a new study by the National Institutes of Health (NIH), part of the U.S. Department of Health and Human Services (HHS). PFAS are a large group of chemicals used in common consumer products. Often referred to as "forever chemicals," PFAS do not break down easily in the environment and can remain in the body for years.

The study found that higher blood plasma levels of two of these substances, perfluorooctanoic acid (PFOA) and perfluorooctanesulfonic acid (PFOS), were associated with a higher incidence of ER-negative breast cancer. No clear association was observed between the two chemicals and breast cancer risk overall.

"Women deserve clear answers about how chemicals in their environment may affect their health," said HHS Secretary Robert F. Kennedy Jr. "This NIH study links two forever 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."

ER-negative tumors lack receptors that allow the hormone estrogen to help cancer cells grow. Compared with breast cancers that respond to the hormone estrogen, ER-negative breast cancers tend to be more aggressive and have worse outcomes. Scientists know less about what raises the risk of this type of breast cancer.

"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. The findings are reported in the Journal of Clinical Oncology.

NIH researchers and their collaborators measured 17 PFAS in blood, collected years before women were diagnosed with cancer. Women in the group with the highest PFOA levels had a 67% higher rate of ER-negative breast cancer than those in the lowest group. For PFOS, the rate was 93% higher, or nearly twice as high. These numbers describe relative differences between groups, not an individual woman's chance of getting breast cancer.

The research drew on the Sister Study, led by NIH's National Institute of Environmental Health Sciences (NIEHS). The larger study enrolled 50,884 women ages 35–74 in the United States and Puerto Rico from 2003 to 2009. None had breast cancer when they joined the Sister Study, but each had a full or half-sister who had been previously diagnosed with breast cancer. For the PFAS study, researchers included 1,609 women who developed breast cancer and a comparison sample of 2,269 women.

"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."

Because the strongest associations involved tumors without hormone receptors, the authors suggest that PFAS may affect cancer risk through other nonhormonal biologic pathways. Possible pathways include changes in gene activity or the immune system. However, this study did not test those explanations. The authors say future studies should evaluate people with higher PFAS exposure and those in groups more affected by ER-negative breast cancer.

Although most individuals have measurable levels of PFOA and PFOS in their bodies, these compounds have been largely phased out and replaced with new PFAS compounds. "More research is needed, particularly evaluating the risk of breast cancer associated with newer replacement PFAS chemicals," White said.

Publication details

Per- and Polyfluoroalkyl Substance Exposure and Breast Cancer Incidence in the Sister Study, Journal of Clinical Oncology (2026). DOI: 10.1200/JCO-26-00318

Journal information: Journal of Clinical Oncology

Key medical concepts

perfluorooctanoic acidperfluorooctane sulfonic acid

Clinical categories

OncologyWomen's healthCommon illnesses & Prevention Provided by National Institutes of Health Who's behind this story?

Gaby Clark

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