Perfluorinated alkylated substances serum concentration and breast cancer risk: Evidence from a nested case-control study in the French E3N cohort

By Francesca Romana Mancini, Germano Cano-Sancho, Juliette Gambaretti, Philippe Marchand, Marie-Christine Boutron-Ruault, Gianluca Severi, Patrick Arveux, Jean-Philippe Antignac, and Marina Kvaskoff
Int. J. Cancer
April 22, 2019
DOI: 10.1002/ijc.32357

Endocrine-disrupting chemicals are proposed to increase breast cancer (BC) incidence. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), two perfluorinated alkylated substances (PFASs), are suspected to be ubiquitously present in the blood of human population worldwide. We investigated the associations between serum concentrations of these substances and BC risk. E3N is a cohort of 98,995 French women born in 1925-1950 and followed-up since 1990. We sampled 194 BC cases and 194 controls from women with available blood samples. Serum concentrations of PFASs were measured by LC-MS/MS. Adjusted conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). All statistical tests were two-sided. While PFASs concentrations were not associated with BC risk overall, we found positively linear associations between PFOS concentrations and the risk of ER+ (3 quartile: OR=2.22 (CI=1.05-4.69); 4 quartile: OR=2.33 (1.11-4.90); P =0.04) and PR+ tumors (3 quartile: OR=2.47 (CI=1.07-5.65); 4 quartile: OR=2.76 (CI=1.21-6.30); P =0.02). When considering receptor-negative tumors, only the 2 quartile of PFOS was associated with risk (ER-: OR=15.40 (CI=1.84-129.19); PR-: OR=3.47 (CI=1.29-9.15)). While there was no association between PFOA and receptor-positive BC risk, the 2 quartile of PFOA was positively associated with the risk of receptor-negative tumors (ER-: OR=7.73 (CI=1.46-41.08); PR-: OR=3.44 (CI=1.30-9.10)). Circulating levels PFASs circulating levels were differentially associated with BC risk. While PFOS concentration was linearly associated with receptor-positive tumors, only low concentrations of PFOS and PFOA were associated with receptor-negative tumors. Our findings highlight the importance of considering exposure to PFASs as a potential risk factor for BC. 

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