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. 2025 Mar 28;24(1):13.
doi: 10.1186/s12940-025-01168-5.

Plasma perfluoroalkyl substances and breast cancer risk in Brazilian women: a case-control study

Hiroaki Itoh  1   2 , Kouji H Harada  3 , Gerson Shigeaki Hamada  4 , Zhaoqing Lyu  3 , Tomoko Fujitani  3 , Mariko Harada Sassa  3 , Taiki Yamaji  5 , Shoichiro Tsugane  6   7 , Motoki Iwasaki  5   7
Affiliations

Plasma perfluoroalkyl substances and breast cancer risk in Brazilian women: a case-control study

Hiroaki Itoh et al. Environ Health. .

Abstract

Background: Per- and polyfluoroalkyl substances (PFAS) are persistent environmental pollutants, and have been detected in human blood. Although PFAS may increase the risk of breast cancer in humans, findings from previous epidemiological studies on the link between PFAS and breast cancer are controversial. Additionally, most studies of PFAS to date did not distinguish between isomers. Here, we examined the association of PFAS exposure and breast cancer risk in Brazilian women, who represent a racially and ethnically diverse group.

Methods: We conducted a case-control study of 471 women with breast cancer and 471 matched controls attending hospitals in São Paulo, Brazil from 2001 to 2006. Plasma concentrations of PFAS congeners were measured using in-port arylation gas chromatography-isotope dilution mass spectrometry with electron capture negative ionization. Linear and branched PFAS isomers were isolated and quantified separately. We derived multivariable-adjusted odds ratios and 95% confidence intervals for breast cancer and hormone-receptor subtypes according to plasma PFAS concentration.

Results: In overall analyses, higher plasma concentrations of n-perfluoroheptane sulfonate (n-PFHpS), perfluoro-3-methyl-heptane sulfonate (3 m-PFOS), and n-perfluorononanoic acid were significantly associated with increased risk of breast cancer. Adjusted odds ratios for low, medium, and high n-PFHpS concentrations were 1.00, 1.28, and 2.00 (95% confidence interval = 1.15, 3.48), respectively (P for trend = 0.015). Furthermore, plasma 3 m-PFOS concentration and total perfluorooctanoic acid concentration were significantly associated with increased risk of breast cancer among mixed-ethnicity women. In Caucasian women, a higher plasma perfluoro-4-methyl-heptane sulfonate concentration was also associated with increased risk of breast cancer. Increased plasma n-PFHpS concentration was significantly associated with higher risk of hormone receptor-positive breast cancer but not with increased risk of hormone receptor-negative breast cancer.

Conclusions: Several plasma PFAS appear to increase the risk of breast cancer. Our findings suggest the importance of isomer analysis, subgroup analysis by ethnicity, and breast cancer subtype analysis for accurately characterizing this risk.

Clinical trial number: Not applicable.

Keywords: Breast cancer; Multiethnic; Per- and polyfluoroalkyl substances; Southern hemisphere.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: The study protocol was reviewed and approved by Comissão Nacional de Ética em Pesquisa (Brasília, Brazil); the institutional review board of the National Cancer Center (Tokyo, Japan); the Research Ethics Committee, Faculty of Medicine, Juntendo University (Tokyo, Japan); and the Kyoto University Graduate School and Faculty of Medicine Ethics Committee (Kyoto, Japan). Written informed consent was obtained from all participants. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

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