Jonathan N. Hofmann

Serum perfluorooctane sulfonate and perfluorooctanoate and risk of postmenopausal breast cancer according to hormone receptor status: An analysis in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial

Abstract Per‐ and polyfluoroalkyl substances (PFAS) are highly persistent endocrine‐disrupting chemicals that may contribute to breast cancer development; however, epidemiologic evidence is limited. We investigated associations between prediagnostic serum levels of perfluorooctane sulfonate (PFOS) and perfluorooctanoate (PFOA) and postmenopausal breast cancer risk, overall and by hormone receptor status, in a nested case‐control study of 621 cases and 621 matched controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. PFOS and PFOA levels were determined based on serum metabolomic profiling performed using ultraperformance liquid chromatography‐tandem mass spectrometry. We used multivariable conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between each PFAS and breast cancer risk, overall, by estrogen receptor (ER) or progesterone receptor (PR) status, and by joint ER/PR status. We found little evidence of association between PFOS or PFOA and breast cancer risk overall. However, in subtype‐specific analyses, we observed statistically significant increased risks of ER+, PR+, and ER+/PR+ tumors for the third vs lowest quartile of serum PFOS (ORs [95% CIs] = 1.59 [1.01‐2.50], 2.34 [1.29‐4.23], and 2.19 [1.21‐3.98], respectively) and elevated but nonstatistically significant ORs for the fourth quartile. Conversely, for PFOA, modest positive associations with ER−, PR−, ER+/PR−, and ER−/PR− tumors were generally seen in the upper quartiles. Our findings contribute evidence supporting positive associations between serum PFOS and hormone receptor‐positive tumors, and possibly between PFOA and receptor‐negative tumors. Future prospective studies incorporating tumor hormone receptor status are needed to better understand the role of PFAS in breast cancer etiology.

Serum concentrations of perfluoroalkyl and polyfluoroalkyl substances and risk of ovarian cancer

Abstract Background Perfluoroalkyl and polyfluoroalkyl substances (PFAS) are persistent, widespread environmental contaminants, and some are endocrine disrupting. Studies of gynecologic cancers are limited; we evaluated ovarian cancer, a rare, often fatal malignancy. Methods This nested case-control study included 318 ovarian cancer cases and 472 individually matched female controls in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, which recruited participants aged 55-74 years from 10 US study centers (1993-2001). We looked at cases through 2016 and quantitated 8 PFAS in prediagnostic serum samples. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) for continuous (log2-transformed) and categorized PFAS concentrations by using conditional logistic regression models, implicitly adjusting for matching factors (age, center, year of random assignment, year of blood draw, race and ethnicity) and adjusting for smoking, body mass index, family history of cancer, menopausal hormone therapy and oral contraceptive use, parity, and number of freeze-thaw cycles. Results We found a positive association with ovarian cancer for a doubling in 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA) concentrations (OR for log2 = 1.24, 95% CI = 1.03 to 1.49) and 62% greater risk among those in the highest quartile (OR for quartile 4 vs quartile 1 = 1.62, 95% CI = 1.03 to 2.54; P for trend = .02). Perfluorooctane sulfonic acid (PFOS) was associated with increased risk (OR for log2 = 1.47, 95% CI = 1.05 to 2.06), with no quartile trend (P for trend = .79). Associations with perfluorononanoic acid (OR for log2 = 1.36, 95% CI = 0.95 to 1.95) and perfluorodecanoic acid (OR for log2 = 1.35, 95% CI = 0.94 to 1.95) were suggested, with nonmonotonic quartile trends (P for trend = .12 to .21). The MeFOSAA associations were strongest in women aged 55-59 years (OR for log 2 = 1.60, 95% CI = 1.13 to 2.27), more moderate in women aged 60-64 years (OR for log2 = 1.31, 95% CI = 0.90 to 1.90), and null among women 65 years of age and older (OR for log2 = 1.02, 95% CI = 0.73 to 1.43; P for heterogeneity = .22). Associations persisted in cases diagnosed 8 years or more after blood collection. Conclusions These findings offer novel evidence for PFAS as ovarian cancer risk factors, particularly PFOS and MeFOSAA, a PFOS precursor.