Perfluorinated chemicals, PFOS and PFOA, enhance the estrogenic effects of 17β‐estradiol in T47D human breast cancer cells

Sonthithai, Pacharapan; Suriyo, Tawit; Thiantanawat, Apinya; Watcharasit, Piyajit; Ruchirawat, Mathuros; Satayavivad, Jutamaad

doi:10.1002/jat.3210

Cited by 68 publications

(23 citation statements)

References 72 publications

(97 reference statements)

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“…reported that PFOS and PFOA have estrogenic activity and antithyroid hormone activity, altering steroid hormone synthesis and the expression of the major steroidogenic genes . On the other hand, another in vitro study, which analyzed PFOA and PFOS estrogenic effects on T47D hormone‐dependent BC cells, found that while these compounds did not have estrogenic activity, they enhanced the effects of estradiol on estrogen‐responsive gene expression, ERK1/2 activation and the growth of the hormone‐deprived T47D cells …”

Section: Discussionmentioning

confidence: 99%

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

Mancini

Cano-Sancho

Gambaretti

et al. 2019

Intl Journal of Cancer

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Endocrine‐disrupting chemicals are proposed to increase breast cancer (BC) incidence. Perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA), two perfluorinated alkylated substances (PFASs), are suspected to be ubiquitously present in the blood of human population worldwide. We investigated the associations between serum concentrations of these substances and BC risk. Etude Epidémiologique auprès de femmes de l'Education Nationale is a cohort of 98,995 French women born in 1925–1950 and followed up since 1990. We sampled 194 BC cases and 194 controls from women with available blood samples. Serum concentrations of PFASs were measured by liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS). Adjusted conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). All statistical tests were two sided. While PFASs concentrations were not associated with BC risk overall, we found positively linear associations between PFOS concentrations and the risk of ER+ (3rd quartile: OR = 2.22 [CI = 1.05–4.69]; 4th quartile: OR = 2.33 [CI = 1.11–4.90]); Ptrend = 0.04) and PR+ tumors (3rd quartile: OR = 2.47 [CI = 1.07–5.65]; 4th quartile: OR = 2.76 [CI = 1.21–6.30]; Ptrend = 0.02). When considering receptor‐negative tumors, only the 2nd quartile of PFOS was associated with risk (ER−: OR = 15.40 [CI = 1.84–129.19]; PR−: OR = 3.47 [CI = 1.29–9.15]). While there was no association between PFOA and receptor‐positive BC risk, the 2nd quartile of PFOA was positively associated with the risk of receptor‐negative tumors (ER−: OR = 7.73 [CI = 1.46–41.08]; PR−: OR = 3.44 [CI = 1.30–9.10]). PFAS circulating levels were differentially associated with BC risk. While PFOS concentration was linearly associated with receptor‐positive tumors, only low concentrations of PFOS and PFOA were associated with receptor‐negative tumors. Our findings highlight the importance of considering exposure to PFASs as a potential risk factor for BC.

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Section: Discussionmentioning

confidence: 99%

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

Mancini

Cano-Sancho

Gambaretti

et al. 2019

Intl Journal of Cancer

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“…In hormone-dependent T47D human breast cancer cells, neither PFOA nor PFOS, by themselves, affected cell proliferation. However, in the presence of estradiol, both chemicals did enhance the effects of estradiol on cell growth as well as the expression of several estrogen-responsive genes and ERK1/2 activation [ 382 ].…”

Section: Evidence Linking Environmental Factors and Breast Cancermentioning

confidence: 99%

State of the evidence 2017: an update on the connection between breast cancer and the environment

et al. 2017

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BackgroundIn this review, we examine the continually expanding and increasingly compelling data linking radiation and various chemicals in our environment to the current high incidence of breast cancer.AbstractSingly and in combination, these toxicants may have contributed significantly to the increasing rates of breast cancer observed over the past several decades. Exposures early in development from gestation through adolescence and early adulthood are particularly of concern as they re-shape the program of genetic, epigenetic and physiological processes in the developing mammary system, leading to an increased risk for developing breast cancer. In the 8 years since we last published a comprehensive review of the relevant literature, hundreds of new papers have appeared supporting this link, and in this update, the evidence on this topic is more extensive and of better quality than that previously available.ConclusionIncreasing evidence from epidemiological studies, as well as a better understanding of mechanisms linking toxicants with development of breast cancer, all reinforce the conclusion that exposures to these substances – many of which are found in common, everyday products and byproducts – may lead to increased risk of developing breast cancer. Moving forward, attention to methodological limitations, especially in relevant epidemiological and animal models, will need to be addressed to allow clearer and more direct connections to be evaluated.

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“…10 Both perfluorinated alkylated substances have been shown to enhance the estrogenic effect of estradiol in vitro. 11 There is also some evidence that PFOS and PFOA could affect estrogen homeostasis during human pregnancy. 12 LC-MS/MS method development.…”

Section: Chemicals and Reagentsmentioning

confidence: 99%

“…Exposure to xenoestrogens may also be a risk factor for hormone-related cancers including those of breast and the reproductive tract, especially during the sensitive, early developmental stages. [11][12][13] The proper assessment of combinatory effects of multiple xenoestrogens are a current key challenge. Numerous studies investigating the potency of individual compounds or compound classes have been published, while data on estrogenic mixtures is scarce.…”

mentioning

confidence: 99%

A Generic LC-MS/MS Exposome Method for the Determination of Xenoestrogens in Biological Matrices

Preindl¹,

Braun²,

Aichinger³

et al. 2019

Preprint

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We are constantly exposed to a variety of environmental contaminants and hormones including those mimicking endogenous estrogens. These highly heterogeneous molecules are collectively referred to as xenoestrogens and hold the potential to affect and alter the delicate hormonal balance of the human body. To monitor exposure and investigate potential health implications, comprehensive analytical methods covering all major xenoestrogen classes are urgently needed but still not available. Herein, we describe an LC-MS/MS method for the simultaneous determination of multiple classes of endogenous as well as exogenous estrogens in human urine, serum and breast milk to enable proper exposure and risk assessment. In total, 75 analytes were included, whereof a majority was successfully in-house validated in the three matrices. Extraction recoveries of validated analytes ranged from 71% to 110% and limits of quantification from 0.015 to 5 µg/L, 0.03 to 14 µg/L, and 0.03 to 4.6 µg/L in urine, serum and breast milk, respec-tively. The applicability of the novel method was demonstrated in proof of principle experiments by analyzing urine from Austrian, and breast milk from Austrian and Nigerian individuals. Thereby, we proved the methods’ feasibility to identify and quantify different classes of xenoestrogens simultaneously. The results illustrate the general importance of multi-class exposure assessment in the context of the exposome paradigm. Specifically, they highlight the need for estimating total estrogenic burden rather than single analyte or chemical class measurements and its potential impact in endocrine disruption and hormone related diseases including cancers.<br>

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Perfluorinated chemicals, PFOS and PFOA, enhance the estrogenic effects of 17β‐estradiol in T47D human breast cancer cells

Cited by 68 publications

References 72 publications

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

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

State of the evidence 2017: an update on the connection between breast cancer and the environment

A Generic LC-MS/MS Exposome Method for the Determination of Xenoestrogens in Biological Matrices

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