A case-control study of the association between per- and polyfluoroalkyl substances (PFAS) and risk of postmenopausal breast cancer in the Danish diet cancer and health cohort.

BACKGROUND

Exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with breast cancer, however findings have been conflicting and few studies have examined cancer subtypes or risk among subgroups of women.

METHODS

We used an individually matched case-control design, nested within the Danish Diet Cancer and Health cohort. We identified 500 incident breast cancer cases with available plasma samples among postmenopausal women aged 50 to 64 years in the Danish Cancer Registry and for each case, we randomly selected from the study base one control woman enrolled within 180 days of the case and of the same age with an available sample. Plasma samples, taken at enrollment in 1993-97, were identified in the biobank and concentrations of PFAS were measured in 2025. Data were analyzed using logistic regression.

RESULTS

No association between PFAS exposure and overall breast cancer was found with odds ratios per interquartile range of perfluorooctanoic acid (PFOA) = 0.89 (0.76-1.05), of perfluorohexane sulfonic acid (PFHxS) = 1.02 (0.98-1.06), of perfluorononanoic acid (PFNA) = 0.94 (0.87-1.02), of perfluoroheptanesulfonic acid (PFHpS) = 0.94 (0.79-1.11), of perfluorooctane sulfonate (PFOS) = 0.93 (0.78-1.11), and of N-ethyl perfluorooctane sulfonamido acetic acid (N-EtFOSAA) = 0.93 (0.79-1.09). Likewise, no clear association was observed for subtypes of breast cancer (ER, PR and HER2 status) nor with tumor size, or lymph node involvement. PFHpS, PFOS and N_EtFOSAA exposure was associated with a non-significant increased risk of breast cancer among current and previous hormone therapy (HT) users, whereas no association was found for never users.

CONCLUSION

We found no association between exposure to six commonly used PFAS and overall breast cancer risk in postmenopausal women. The results indicated that exposure to some PFAS might be associated with increased risk of breast cancer among current/previous HT users. These results warrant replication in future prospective studies.