The incidence of breast cancer is continuing to rise in Western countries, and there has been increasing interest in understanding the contribution of exposure to endocrine disrupting chemicals (EDCs) to this increase. A large group of EDCs, for which the long-term health effects remain uncharacterized with regards to breast cancer, are perfluoroalkyated compounds (PFAS). PFAS are a group of synthetic compounds that are stable, persistent and bioaccumulative. Among PFAS, perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) are the most frequent compounds found in food and are ubiquitously present in the blood of Western populations. The objective of this study was to investigate the associations between serum levels of PFOS and PFOA and the risk of breast cancer in a nested case-control study.

E3N (“Étude Épidémiologique auprès de femmes de l’Éducation Nationale”) is a French prospective cohort that enrolled 98,995 women aged 40–65 years at inclusion in 1990. After inclusion, women were followed-up every 2–3 years through self-administered questionnaires. We identified 198 cases of incident invasive breast cancer with available blood samples, collected between 1994 and 1999. For each case, one control was randomly sampled from women in the cohort who were free of breast cancer at the time of diagnosis of the corresponding case. Controls were matched to cases by age and menopausal status at blood collection, study center, and year of blood collection. Serum levels of PFOS and PFOA were measured for each woman included in the study (n=396) by liquid chromatography coupled to tandem mass spectrometry. Women were divided into quintiles based on serum levels of PFOS and PFOA separately. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs). After running univariate models, all models were adjusted for total serum lipids, body mass index, smoking status, physical activity, education level, family history of breast cancer, history of benign breast disease, parity/age at first full-term pregnancy, total breastfeeding duration, age at menarche, age at menopause, current use of menopausal hormone therapy, use of hormonal contraceptives, adherence to a Western dietary pattern and adherence to a Mediterranean dietary pattern.

The average serum levels of PFOS and PFOA were 19.08ng/mL (Standard deviation [SD] 8.19) and 7.32ng/mL (SD 3.49), respectively. Since serum levels were right skewed, all values were log-transformed in order to achieve a normal distribution. In univariate analyses, no statistically significant association was found between PFOS or PFOA serum levels and breast cancer risk. After adjustment, PFOS serum levels were positively and linearly associated with breast cancer risk (highest quintile: OR 3.46, 95% CI 1.40–8.52, compared with the lowest; P_trend=0.006). In contrast, when considering PFOA levels, only women in the 2nd quintile group had a significantly increased risk of breast cancer (OR 2.41, 95% CI 1.08–5.35), suggesting a non-monotonic dose-response pattern.

This study provides evidence of an association between circulating levels of PFAS and breast cancer risk. In particular, PFOS was linearly associated with breast cancer risk starting from internal values equal to 13.3ng/mL, while only a low dose effect was highlighted for PFOA, with a increased risk for values between 4.7 and 5.8ng/mL. This study reflects real-life exposure of a non-professionally exposed population of women in France. Our results highlight the importance of focusing on low-dose effects when studying EDCs, as well as the importance of considering exposure to EDCs, and in particular to PFAS, as a relevant risk factor for breast cancer, thus as a serious public health issue.