Women with higher blood levels of two common per- and polyfluoroalkyl substances face a higher incidence of developing estrogen receptor-negative breast cancer, according to a new National Institutes of Health analysis published in the Journal of Clinical Oncology.
The Blood Plasma Findings on PFOA and PFOS
The research measured 17 different PFAS compounds in blood samples collected years before the participating women received a cancer diagnosis. Investigators focused specifically on perfluorooctanoic acid, known as PFOA, and perfluorooctanesulfonic acid, commonly called PFOS. These synthetic compounds belong to a large group often dubbed “forever chemicals” because they resist environmental breakdown and can remain in the body for years.
The numbers from the study show distinct differences between exposure tiers. Women falling into the group with the highest PFOA blood plasma levels experienced a 67% higher rate of ER-negative breast cancer compared to those in the lowest exposure group. For PFOS, the rate was 93% higher, or nearly twice as high. The analysis did not, however, find a clear association between these two specific chemicals and overall breast cancer risk.
Legacy PFAS Drive Aggressive ER-Negative Breast Tumors
ER-negative breast tumors lack the specific receptors that allow the hormone estrogen to help cancer cells grow. Because they do not respond to hormone therapies that target estrogen receptors, these aggressive cancers tend to have worse outcomes. Medical science knows less about what triggers this specific subtype compared to hormone-responsive tumors.
Alexandra White, Ph.D., an NIH Stadtman Investigator who led the study, explained the significance of these findings. 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,
she stated.
1/3 NIH study: PFOA & PFOS “forever chemicals” linked to higher rates of ER-negative breast cancer. Association ≠ causation. Watch:https://t.co/MtdBETi8KC NIH:https://t.co/OA2k0vZYph@SusanGKomen @BCRFcure
Sister Study Links Toxic Chemicals to Cancer Diagnoses
The study drew upon data from the Sister Study, a large-scale project led by the NIEHS that enrolled 50,884 women ages 35 to 74 across the United States and Puerto Rico between 2003 and 2009. None of the participants had breast cancer at enrollment, but each had a sister previously diagnosed with the disease. The specific analysis on PFAS evaluated 1,609 women who developed breast cancer alongside a comparison sample of 2,269 women.
Robert F. Kennedy, Jr., HHS Secretary, addressed the public health implications following the publication. Women deserve clear answers about how chemicals in their environment may affect their health,
Kennedy noted. 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.
People Can Reduce Exposure to Persistent Chemicals
Che-Jung Chang, Ph.D., a former NIH research fellow and current researcher at DLH, a scientific research organization, who served as the study’s first author, emphasized that exposure remains a variable people can influence. 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,
Chang said.
Because the strongest associations involved tumors without hormone receptors, the authors suggest that these chemicals may operate through other non-hormonal biologic pathways, such as changes in gene activity or immune system. Although PFOA and PFOS have been largely phased out and replaced with new PFAS compounds, most individuals still retain measurable levels of the legacy compounds in their bodies. White noted that more research is needed, particularly evaluating the risk of breast cancer associated with newer replacement PFAS chemicals.
