Breast cancer risk and serum levels of per- and poly-fluoroalkyl substances: a case-control study nested in the California Teachers Study

Abstract

BackgroundPer- and poly- fluoroalkyl substances (PFASs) are a large family of synthetic chemicals, some of which are mammary toxicants and endocrine disruptors. Their potential as breast carcinogens is unclear. Our objective was to evaluate the risk of breast cancer associated with serum PFAS concentrations in a nested case-control study within the California Teachers Study.MethodsParticipants were 902 women with invasive breast cancer (cases) and 858 with no such diagnosis (controls) who provided 10 mL of blood and were interviewed during 2011–2015, an average of 35 months after case diagnosis. PFASs were measured using automated online SPE-HPLC-MS/MS methods. Statistical analyses were restricted to six PFASs with detection frequencies ≥ 95%: PFOA (Perfluorooctanoic acid), PFNA (Perfluorononanoic acid), PFUnDA (Perfluoroundecanoic acid), PFHxS (Perfluorohexane sulfonic acid), PFOS (Perfluorooctane sulfonic acid), and MeFOSAA (2-(N-Methyl-perfluorooctane sulfonamido) acetic acid. Unconditional logistic regression was used to calculate adjusted odds ratios (ORs), estimating the breast cancer risk associated with each PFAS.ResultsFor all cases of invasive breast cancer, none of the adjusted ORs were statistically significant but marginally significant ORs < 1.0 were observed for PFUnDA and PFHxS (p-trend = 0.08). Adjusted ORs < 1.0 for PFUnDA and PFHxS were statistically significant (p ≤ 0.05) among the 107 cases with hormone-negative tumors but not the 743 with hormone-positive tumors.ConclusionOverall, these findings do not provide evidence that serum PFAS levels measured after diagnosis are related to breast cancer risk. The few inverse associations found may be due to chance or may be artifacts of study design. Future studies should incorporate information about genetic susceptibility, endogenous estrogen levels, and measurements of PFASs prior to diagnosis and treatment.Electronic supplementary materialThe online version of this article (10.1186/s12940-018-0426-6) contains supplementary material, which is available to authorized users.

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

“…No association was found between PFOS or PFOA serum concentrations and BC risk neither in a case‐control study nested in the Danish National Birth Cohort, nor in the case‐control study nested in the California Teachers Study . Concerning the case‐control study nested in the Danish National Birth Cohort (based on 250 cases and 233 controls), it should be noted that there are two main differences between this study and ours: first, the Danish study was conducted in a younger population for whom the average age at BC diagnosis was 40.8 years, while in our study the average age at diagnosis was 68.4 years.…”

“…With regard to the case‐control study nested in the California Teachers Study (based on 902 cases and 858 controls), the main difference compared to our study is that cases' blood sampling was performed post‐diagnosis and posttreatment. As for the Inuit studies, the reverse causation bias cannot be fully ruled out due to the fact that that PFOS and PFAS internal levels could have been affected both by the onset and treatment of BC …”

“…17 No association was found between PFOS or PFOA serum concentrations and BC risk neither in a case-control study nested in the Danish National Birth Cohort, nor in the casecontrol study nested in the California Teachers Study. 18,19 Concerning the case-control study nested in the Danish National Birth Cohort (based on 250 cases and 233 controls), it should be noted that there are two main differences between Table 3. Conditional logistic regression models to estimate the association between quartiles of serum levels of PFOS and breast cancer risk in postmenopausal women: adjusted odds ratios (ORs) and 95% confidence intervals (CIs) (N = 388) Model 3: adjusted for total serum lipids (unit), BMI (kg/m 2 ), smoking status (non-smoker vs. smoker), physical activity (MET-h/week), education level (≤14 vs. >14 years), personal history of benign breast disease (yes vs. no), family history of breast cancer (yes vs. no), parity*age at first full-term pregnancy (nulliparous, 1 or 2 children and <25 years old at delivery, ≥3 children and <25 years old at delivery, ≥25 years old at delivery), total breastfeeding duration (never, ≤6 months, >6 months), age at menarche, age at menopause, use of oral contraceptives (ever vs. never), current use of menopausal hormone therapy (yes vs.no), score of adherence to the Western diet and to the Mediterranean diet, age (years) at blood draw, BMI (kg/m 2 ) at blood draw, menopausal status (premenopausal vs. postmenopausal) at blood draw and year of blood draw.…”

“…As for the Inuit studies, the reverse causation bias cannot be fully ruled out due to the fact that that PFOS and PFAS internal levels could have been affected both by the onset and treatment of BC. 19 Few animal and in vitro studies are available on the effects of PFOS and PFOA on the mammary gland. In order to assess the potential chronic toxicity and tumorigenicity of PFOA, Butenhoff et al conducted a 2-year dietary study on rats demonstrating that gestational exposure to this compound was Table 5.…”

Serum Levels of Commonly Detected Persistent Organic Pollutants and Per- and Polyfluoroalkyl Substances (PFASs) and Mammographic Density in Postmenopausal Women

“…Data on other classes of POPs such as polybrominated diphenyl ethers (PBDEs) and per-and poly-fluoroalkyl substances (PFASs) remain scarce and inconsistent [12][13][14][15][16][17][18][19][20][21][22]. Five studies using post-diagnostic samples have investigated serum or adipose-level PBDEs in relation to breast cancer risk [12,[14][15][16]22].…”