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Meta-Analysis
. 2024 Aug 5;193(8):1182-1196.
doi: 10.1093/aje/kwae010.

Exposure to per- and polyfluoroalkyl substances and breast cancer risk: a systematic review and meta-analysis of epidemiologic studies

Che-Jung Chang  1 , Jennifer L Ish  1 , Vicky C Chang  2 , Meklit Daniel  1 , Rena R Jones  2 , Alexandra J White  1
Affiliations
Meta-Analysis

Exposure to per- and polyfluoroalkyl substances and breast cancer risk: a systematic review and meta-analysis of epidemiologic studies

Che-Jung Chang et al. Am J Epidemiol. .

Abstract

We synthesized the epidemiologic evidence on the associations between per- and polyfluoroalkyl substances (PFAS) exposure and breast cancer risk. Our systematic review and meta-analysis included 18 and 11 articles, respectively, covering studies up to February 2023. The summary relative risks (RRs) estimated by random-effects meta-analyses did not support an association between PFAS and overall breast cancer risk (eg, a natural log (ln)-unit increase in serum/plasma concentrations [ng/mL] for perfluorooctanoate [PFOA] RR = 0.95; 95% CI, 0.77-1.18; perfluorooctane sulfonate [PFOS] RR = 0.98; 95% CI, 0.87-1.11). However, when limiting to studies that assessed exposures prior to a breast cancer diagnosis, we observed a positive association with PFOA (a ln-unit increase, RR = 1.16; 95% CI, 0.96-1.40). We also observed some possible heterogeneous associations by tumor estrogen and progesterone receptor status among postmenopausal breast cancer cases. No meaningful changes were observed after excluding the studies with high risk of bias (Tier 3). Based on the evaluation tool developed by the National Toxicology Program, given the heterogeneity across studies and the variability in timing of exposure measurements, the epidemiologic evidence needed to determine the association between PFAS exposure and breast cancer remains inadequate. Our findings support the need for future studies with improved study designs to determine this association.

Keywords: PFAS; breast cancer; epidemiologic study; meta-analysis; per- and polyfluoroalkyl substances; systematic review.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Figure 1
Figure 1
Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram. PFAS, per- and polyfluoroalkyl substances.
Figure 2
Figure 2
Summary of the risk-of-bias assessment, for the included studies across multiple countries, up to 2023. A) Risk of bias for each study; B) number of studies by each risk-of-bias domain and rating.
Figure 3
Figure 3
Reported relative risks, 95% CIs, and meta-analyses for per-natural-log-unit increase in serum/plasma per- and polyfluoroalkyl substances (PFAS) concentrations (ng/mL) and breast cancer risk, overall and by timing of blood sample collection, across multiple countries, up to 2023. A) perfluorooctanoate (PFOA); B) perfluorooctane sulfonate (PFOS); C) perfluorohexane sulfonate (PFHxS); D) perfluorononanoate (PFNA). Effect estimates from Chang et al, Mancini et al, and Velarde et al were provided by authors. n, number of studies; formula image, Higgins and Thompson’s statistic; formula image, Cochran’s Q statistic.
Figure 4
Figure 4
Reported relative risks, 95% CIs, and meta-analyses for per-natural-log-unit increase in serum/plasma perfluorooctanoate (PFOA) concentrations (ng/ml) and breast cancer risk by estrogen receptor (ER) and progesterone receptor (PR) status among overall and postmenopausal breast cancer diagnoses, across multiple countries, up to 2023. Test for subgroup difference: ER− vs ER+, P = 0.77; postmenopausal ER+ vs postmenopausal ER−, P = 0.16; PR− vs PR+, P = 0.51; postmenopausal PR+ vs postmenopausal PR−, P = 0.57. Effect estimates from Chang et al, Itoh et al, and Mancini et al were provided by authors. The outcomes were “ER+ or PR+” for Hurley et al and “ER+ and PR+” for Itoh et al in our ER+ and PR+ analyses, and “ER− and PR−” for both Hurley et al and Itoh et al in our ER- and PR- analyses.
Figure 5
Figure 5
Reported relative risks, 95% CIs, and meta-analyses for per-natural-log-unit increase in serum/plasma perfluorooctane sulfonate (PFOS) concentrations (ng/mL) and breast cancer risk by estrogen receptor (ER) and progesterone receptor (PR) status among overall and postmenopausal breast cancer diagnoses, across multiple countries, up to 2023. Test for subgroup difference: ER− vs ER+ P = 0.11; postmenopausal ER+ vs postmenopausal ER− P = 0.62; PR− vs PR+ P = 0.16; postmenopausal PR+ vs postmenopausal PR− P = 0.03. Effect estimates from Chang et al, Itoh et al, and Mancini et al were provided by authors. The outcomes were “ER+ or PR+” for Hurley et al and “ER+ and PR+” for Itoh et al in our ER+ and PR+ analyses, and “ER− and PR−” for both Hurley et al and Itoh et al in our ER− and PR− analyses.
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