PFOA and PFOS linked to ER-negative breast cancer in Sister Study cohort
In a case-cohort analysis of 1,609 cases, higher plasma PFOA and PFOS were associated with ER-negative breast cancer, a type with few established risk factors.
A case-cohort study within the Sister Study, published online on November 5, 2026 in the Journal of Clinical Oncology, examined 17 per- and polyfluoroalkyl substances (PFAS) in plasma collected before diagnosis. It included 1,609 breast cancer cases and 2,269 subcohort participants doi.org
Journal of Clinical Oncologydoi.orgOpen source ↗. The authors, led by Chang C-J, report that PFOA and PFOS were associated with estrogen receptor (ER)-negative tumors.
The Sister Study enrolled more than 50,000 women aged 35 to 74 years who have a full or half-sister with a breast cancer diagnosis.
Design and methods
To improve statistical power, the researchers oversampled ER-negative cases: the analysis included 324 ER-negative and 1,120 ER-positive tumors. PFAS were quantified using liquid chromatography-high-resolution mass spectrometry. Sampling-weighted Cox models estimated associations with overall breast cancer incidence and by hormone receptor status, adjusting for confounders and coexposures.
Median baseline age was 57.2 years in the case population and 55.6 years in the subcohort, with median follow-up of 5.9 and 9.7 years, respectively. PFAS concentrations were similar in cases and the subcohort and comparable to levels in the US population survey NHANES.
Associations by receptor status
Comparing the highest and lowest exposure quartiles, ER-negative tumors were positively associated with PFOA (hazard ratio 1,67; 95% CI 1,10 to 2,53) and PFOS (hazard ratio 1,93; 95% CI 1,15 to 3,22) doi.org
Journal of Clinical Oncologydoi.orgOpen source ↗. N-MeFOSAA showed a possible association (hazard ratio 1,42; 95% CI 0,99 to 2,04). PFTrDA was inversely associated with ER-negative tumors (hazard ratio 0,63; 95% CI 0,41 to 0,97).
PFOSA, detected in 6.9% of samples, was positively associated with ER-positive tumors when detectable versus nondetectable (hazard ratio 1,36; 95% CI 1,03 to 1,81). No associations were found between PFOA or PFOS and ER-positive tumors.
The meta-analysis of seven studies with prediagnostic blood PFAS measurements gave a relative risk of 1,30 (95% CI 1,05 to 1,62) for PFOA and 1,20 (95% CI 0,91 to 1,58) for PFOS with ER-negative breast cancer. The authors concluded that PFOA and PFOS may increase ER-negative breast cancer risk, and recommended that future studies support targeted prevention and characterize newer PFAS replacement chemicals.
