NIH Study Links Two Common PFAS to Increased Risk of Aggressive Breast Cancer

November 5, 2026

National Institutes Of Health

Overview

In a Sister Study analysis, higher prediagnostic blood concentrations of PFOA and PFOS were associated with higher incidence of estrogen receptor-negative (ER-negative) breast cancer. The highest exposure groups had 67% and 93% higher rates, respectively, than the lowest groups; neither chemical showed a clear association with overall breast cancer risk.

Background

Per- and polyfluoroalkyl substances (PFAS) are a broad class of chemicals used in consumer products that degrade slowly in the environment and may persist in the body. ER-negative breast cancers lack estrogen receptors and are generally more aggressive and associated with poorer outcomes than estrogen-responsive breast cancers. The article notes that fewer risk factors are established for ER-negative disease. Evidence syntheses cited in the supplied context have not found a clear association between PFAS and overall breast cancer risk.

Data Highlights

Measure	Finding	Study context
PFOA and ER-negative breast cancer	67% higher rate in the highest versus lowest blood-level group	Prediagnostic blood concentrations; relative difference between groups
PFOS and ER-negative breast cancer	93% higher rate in the highest versus lowest blood-level group	Prediagnostic blood concentrations; relative difference between groups
Overall breast cancer risk	No clear association with either PFOA or PFOS	Reported by the NIH analysis
PFAS analysis population	1,609 women who developed breast cancer and 2,269 comparison participants	Drawn from the Sister Study; participants had a sister with breast cancer
PFAS assessed	17 substances	Measured in blood samples collected years before cancer diagnoses

Key Findings

The NIH analysis associated higher prediagnostic plasma concentrations of PFOA and PFOS with increased incidence of ER-negative breast cancer.
The highest PFOA group had a 67% higher rate of ER-negative disease than the lowest group; the corresponding difference for PFOS was 93%. These are relative group differences, not individual probabilities.
The analysis found no clear association between either chemical and overall breast cancer risk.
Researchers assessed 17 PFAS in the Sister Study, which recruited 50,884 women aged 35–74 years in the United States and Puerto Rico from 2003 to 2009; the PFAS analysis included 1,609 cases and 2,269 comparison participants.
The investigators reported that a meta-analysis of earlier research supported the ER-negative breast cancer finding. The supplied context also describes prior evidence syntheses as finding no clear association between PFAS and overall breast cancer risk.
The authors proposed non-hormonal pathways, including altered gene activity or immune-system effects, as possible explanations, but the study did not examine these mechanisms. They called for further research, including assessment of newer PFAS replacements.

Clinical Implications

The findings describe an association and do not establish that PFOA or PFOS causes ER-negative breast cancer. The authors state that further research is needed, particularly in populations with greater PFAS exposure and for newer replacement PFAS; the supplied material does not report a change to breast cancer screening guidance based on PFAS exposure.

Conclusion

Higher PFOA and PFOS concentrations were associated with ER-negative breast cancer incidence in this analysis, while no clear association with overall breast cancer risk was observed. The authors identify further research as necessary to clarify the findings and assess newer PFAS.