Abstract

There is increasing recognition that environmental exposure to chemicals, such as endocrine-disruptive chemicals (EDCs), contributes to the development of breast cancer. Parabens are a group of EDCs commonly found in personal care products, foods, and pharmaceuticals. Systemic exposure to parabens has been confirmed by the ubiquitous detection of parabens in human blood and urine samples. Although evidence from in vivo and epidemiological studies linking parabens exposure to breast cancer is limited, the current evidence suggests that parabens may negatively interfere with some endocrine and intracrine targets relevant to breast carcinogenesis. So far, most studies have focused on a single paraben’s effects and the direct modulating effects on estrogen receptors or the androgen receptor in vitro. Recent studies have revealed that parabens can modulate local estrogen-converting enzymes, 17β-hydroxysteroid dehydrogenase 1 and 2 and increase local estrogen levels. Also, parabens can crosstalk with the human epidermal growth factor receptor 2 (HER2) pathway and work with ER signaling to increase pro-oncogenic c-Myc expression in ER+/HER2+ breast cancer cells. Future studies investigating paraben mixtures and their crosstalk with other EDCs or signaling pathways both in vitro and in vivo in the context of breast cancer development are warranted.

Highlights

  • Academic Editors: Zhaomin Dong, Breast cancer remains the second leading cause of cancer deaths in women in the US in 2021

  • We summarize the current advances in understanding paraben exposure in humans and the mechanisms by which parabens may increase breast cancer risks

  • The estimated total intake of parabens via personal care product usage ranges from 31–766 μg/kg body weight, with infants being at the upper end [11]

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Summary

Introduction

Academic Editors: Zhaomin Dong, Breast cancer remains the second leading cause of cancer deaths (only second to lung cancer) in women in the US in 2021. The average risk of a woman developing breast cancer at some time in her life is about 13% [1]. The most commonly known modifiable risk factors for breast cancer are obesity, sedentary lifestyle, having a first child after 30, post-menopausal hormone and oral contraceptives use, and xenoestrogen exposure [3]. A growing body of evidence from animal and human studies links exposure to environmental chemicals with increased risks of developing breast cancer. Emerging evidence has revealed the endocrine-disrupting propensity of parabens based on their adverse impact on development and reproduction from both in vitro and in vivo studies [9,10]. We summarize the current advances in understanding paraben exposure in humans and the mechanisms by which parabens may increase breast cancer risks

Human Parabens Exposure
Parabens Exposure and Breast Cancer
Limitations
Estrogenic Effects of Parabens
The Nongenomic Activity of Parabens
Intracrinology
Antiandrogenic Effects of Parabens
Findings
Crosstalk with Human Epidermal Growth Factor Receptor 2 Pathway by Parabens
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