The findings, published in the Journal of Clinical Oncology, add to growing questions about the long-term health effects of per- and polyfluoroalkyl substances (PFAS), often called ‘forever chemicals’ because they resist breaking down in the environment and can accumulate in the human body for years.
To investigate the possible connection, NIH scientists and their collaborators examined blood samples collected years before participants received a cancer diagnosis. They measured concentrations of 17 different PFAS chemicals in 1,609 women who subsequently developed breast cancer and a comparison group of 2,269 women. The data came from the Sister Study, a major research project conducted by NIH’s National Institute of Environmental Health Sciences that enrolled 50,884 women between 2003 and 2009.
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. For PFOS, the highest exposure group showed a 93% higher rate, nearly twice that of the lowest group. These percentages represent relative differences between groups rather than the absolute probability that an individual woman will develop breast cancer. The findings establish an association, not proof that the chemicals directly cause the disease.
ER-negative breast cancer differs from more common forms 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. Despite their severity, researchers still have relatively little information about risk factors for ER-negative 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.
HHS Secretary Robert F. Kennedy, Jr. said: “Women deserve clear answers about how chemicals in their environment may affect their health. 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.”
Although PFOA and PFOS have largely been phased out and replaced with other PFAS compounds, measurable amounts of both substances are still present in most people’s bodies. The researchers say additional investigations should focus on populations with greater PFAS exposure, as well as groups that experience higher rates of ER-negative breast cancer.
“More research is needed, particularly evaluating the risk of breast cancer associated with newer replacement PFAS chemicals,” White said.
First author Che-Jung Chang, Ph.D., who previously worked as an NIH research fellow and is now at the scientific research organization DLH, noted: “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.”
The research received support from NIEHS grants Z01ES044005; Z1AES103332; and R01ES032831.