Associations between legacy and emerging per and polyfluoroalkyl substances (PFAS) bioaccumulation and clinicopathological characteristics in breast cancer

Abstract

Inroduction Per and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants with endocrine-disrupting and carcinogenic potential. However, their bioaccumulation profiles and clinical relevance in human breast cancer remain largely unexplored. Methods In this preliminary study we quantified the absolute concentrations of 33 PFAS congeners (ng/g) in paired tumour and adjacent non-tumorous tissues from 11 breast cancer patients (n = 11) using LC–MS/MS to evaluate their tissue distribution and clinical correlations. Results The detection rates for six compounds (HFPOTA, PFOA, PFNA, PFUnDA, PFOS, and 6:2Cl-PFESA) were greater than 40%. In paired samples, several congeners showed higher concentrations in tumour than in adjacent non-tumorous tissue; using a two-sided exact Wilcoxon signed-rank test with Hodges–Lehmann effect sizes, tumour enrichment remained significant after Benjamini–Hochberg correction for HFPOTA (q = 0.041), PFNA (q = 0.047) and PFUnDA (q = 0.047). HFPOTA showed by far the highest tissue burden (median 654 ng/g). Clinically, PFOS concentrations were descriptively higher in Luminal B than in Luminal A tumours and were positively correlated with the proliferation marker Ki-67; a high 6:2Cl-PFESA–PR rank correlation was observed in four samples but was not statistically significant on the raw p-value (p ≈ 0.051) and is exploratory. Bioinformatic analyses indicated that computationally predicted shared target genes of PFAS and breast cancer are enriched in the PPAR signaling pathway, lipid metabolism, and steroid hormone biosynthesis. Discussion Collectively, PFAS bioaccumulation was associated with breast cancer clinicopathological characteristics. Because the target genes are predicted rather than experimentally validated and the cohort is small (n = 11), these are exploratory, hypothesis-generating findings that require validation in larger cohorts. This study underscores the need to reassess the biosafety of novel PFAS alternatives and provides new insights into the environmental etiology of breast cancer.