HIGHER blood levels of two widely used ‘forever chemicals’ were associated with greater incidence of oestrogen receptor-negative breast cancer in a new study, although no clear association emerged for breast cancer overall.
The research, examined exposure to per- and polyfluoroalkyl substances (PFAS) before diagnosis. The findings suggest that associations between environmental chemicals and breast cancer may differ according to tumour characteristics.
Researchers conducted a case-cohort analysis within the Sister Study, including 1,609 women who developed breast cancer and a comparison subcohort of 2,269 women. All participants had a sister previously diagnosed with breast cancer.
The team measured 17 PFAS in blood samples collected before diagnosis and examined associations with subsequent cancer incidence. Their statistical models accounted for potential confounding factors and other chemical exposures.
Collecting samples before diagnosis strengthens the assessment of whether exposure preceded disease. However, the observational design cannot establish that the chemicals caused cancer.
Women in the highest quarter of exposure to perfluorooctanoic acid (PFOA) had a 67% higher hazard of ER-negative breast cancer than those in the lowest quarter. For perfluorooctanesulfonic acid (PFOS), the corresponding increase was 93%.
These are relative differences between exposure groups, rather than estimates of an individual woman’s absolute likelihood of developing cancer. The absence of a clear association with breast cancer overall also makes the distinction between tumour subtypes central to interpreting the findings.
A meta-analysis of seven studies using blood samples collected before diagnosis provided additional context. The pooled relative risk for ER-negative disease was 1.30 for PFOA, with a 95% confidence interval of 1.05–1.62. For PFOS, it was 1.20, although the confidence interval of 0.91–1.58 included no association. Evidence across studies was therefore more statistically conclusive for PFOA.
The results support further investigation of environmental exposures in ER-negative breast cancer, while leaving important questions unresolved.
Because participants all had a family history of breast cancer, studies in other populations will help establish how broadly the findings apply. Further research should also distinguish the effects of individual PFAS and examine newer replacement compounds.
For clinicians, the study adds evidence about a possible risk factor. It does not establish a role for routine PFAS blood testing in breast cancer assessment or demonstrate that reducing exposure lowers cancer incidence.
Reference
Chang CJ et al. Per- and polyfluoroalkyl substance exposure and breast cancer incidence in the Sister Study. J Clin Oncol. Published online 5 November 2026. doi:10.1200/JCO-26-00318.
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