Potential Pro-Tumorigenic Effect of Bisphenol A in Breast Cancer via Altering the Tumor Microenvironment

SIMPLE SUMMARY: Bisphenol A (BPA) is primarily used to produce polycarbonate plastics, such as water bottles. Exposure to BPA has been shown to increase the growth of breast cancer cells that depend on estrogen for growth due to its ability to mimic estrogen. More recent studies have suggested that BPA also affects the cellular and non-cellular components that compose tumor microenvironments (TMEs), namely the environment around a tumor, thereby potentially promoting breast cancer growth via altering the TME. The TME plays an essential role in cancer development and promotion. Therefore, it is crucial to understand the effect of BPA on breast TMEs to assess its role in the risk of breast cancer adequately. This review examines the potential effects of BPA on immune cells, fibroblasts, extracellular matrices, and adipocytes to highlight their roles in mediating the carcinogenic effect of BPA, and thereby proposes considerations for the risk assessment of BPA exposure. ABSTRACT: BPA, a chemical used in the preparation of polycarbonate plastics, is an endocrine disruptor. Exposure to BPA has been suggested to be a risk factor for breast cancer because of its potential to induce estrogen receptor signaling in breast cancer cells. More recently, it has been recognized that BPA also binds to the G protein-coupled estrogen receptor and other nuclear receptors, in addition to estrogen receptors, and acts on immune cells, adipocytes, and fibroblasts, potentially modulating the TME. The TME significantly impacts the behavior of cancer cells. Therefore, understanding how BPA affects stromal components in breast cancer is imperative to adequately assess the association between exposure to BPA and the risk of breast cancer. This review examines the effects of BPA on stromal components of tumors to highlight their potential role in the carcinogenic effect of BPA. As a result, I propose considerations for the risk assessment of BPA exposure and studies needed to improve understanding of the TME-mediated, breast cancer-promoting effect of BPA.