THE ARISING · Longevity & Healthspan
Higher Blood PFAS Levels Linked to ER-Negative Breast Cancer in Sister Study
Women with the highest blood levels of PFOA and PFOS had higher rates of estrogen receptor-negative breast cancer in an observational Sister Study analysis. The findings do not establish causality or an individual risk prediction.
The work is an observational study in people. Researchers used a case-cohort design within the Sister Study, which follows women who have a sister with breast cancer. They analysed 1,609 women who developed breast cancer and a comparison subcohort of 2,269 women. The team deliberately oversampled estrogen receptor (ER)-negative cases, including 324 ER-negative and 1,120 ER-positive cases, to give the analysis enough statistical power.
PFAS are per-and polyfluoroalkyl substances, often called forever chemicals. The researchers measured 17 of them in plasma collected before diagnosis, using liquid chromatography-high-resolution mass spectrometry. The models adjusted for confounders and coexposures. ER-negative tumors lack receptors that let estrogen help cancer cells grow.
Women in the highest quarter of PFOA levels had a hazard ratio of 1.67 for ER-negative tumors compared with the lowest quarter (95% confidence interval 1.10 to 2.53). For PFOS, the hazard ratio was 1.93 (95% CI 1.15 to 3.22). In plain terms, the highest-exposure groups had about 67% and 93% higher rates of ER-negative breast cancer. These are comparisons between groups, not a prediction for any one woman.
A third compound, N-MeFOSAA, showed a possible positive link (hazard ratio 1.42, 95% CI 0.99 to 2.04). One other PFAS, PFTrDA, ran in the opposite direction, with a hazard ratio of 0.63 for ER-negative tumors (95% CI 0.41 to 0.97). PFOSA, detected in only 6.9% of samples, was linked to ER-positive tumors (hazard ratio 1.36, 95% CI 1.03 to 1.81).
The authors also pooled their results with six other studies that measured PFAS in blood before diagnosis. In that meta-analysis of seven studies, PFOA was associated with ER-negative breast cancer (relative risk 1.30, 95% CI 1.05 to 1.62). PFOS showed a similar but less certain pattern (relative risk 1.20, 95% CI 0.91 to 1.58). The authors concluded that PFOA and PFOS may increase ER-negative breast cancer risk.
The authors highlight the public-health importance of studying widespread exposures alongside the limited established risk factors for ER-negative disease. The findings warrant further research rather than proving that reducing these exposures prevents cancer.