Endocrine disruptors from the environment affecting breast cancer (Review)
Abstract. Evaluation of carcinogenic substances from the environment is a challenge for scientists. Recently, a novel approach based on 10 key characteristics of human carcinogens classified by the International Agency for Research on Cancer (IARC) has emerged. Carcinogenesis depends on different mechanisms and factors, including genetic, infectious (bacteria, viruses) and environmental (chemicals) factors. Endocrine disruptors are exogenous chemicals that can interfere and impair the function of the endocrine system due to their interaction with estrogen receptors or their estrogen signaling pathways inducing adverse effects in the normal mammary development, originating cancer. They are heterogeneous chemicals and include numerous synthetic substances used worldwide in agriculture, industry and consumer products. The most common are plasticizers, such as bisphenol A (BPA), pesticides, such as dichlorodiphenyltrichloroethane, and polychlorinated biphenyls (PCBs). Xenoestrogens appear to serve an important role in the increased incidence of breast cancer in the United States and numerous other countries. Several studies have demonstrated the role of organochlorine xenoestrogens in breast cancer. Therefore, the overall cumulative exposure of women to estrogens results in an increased risk for this type of cancer. Factors like lifestyle and diet also serve a role in the increased incidence of this disease. The aim of the present study was to analyze these chemical compounds based on the key characteristics given by the IARC, with a special focus on breast cancer, to establish whether these compounds are carcinogens, and to create a model for future analysis of other endocrine disruptors.
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Endocrine-disrupting chemicals: implications for human health
Since reports published in 2015 and 2016 identified 15 probable exposure–outcome associations, there has been an increase in studies in humans of exposure to endocrine-disrupting chemicals (EDCs) and a deepened understanding of their effects on human health. In this Series paper, we have reviewed subsequent additions to the literature and identified new exposure–outcome associations with substantial human evidence. Evidence is particularly strong for relations between perfluoroalkyl substances and child and adult obesity, impaired glucose tolerance, gestational diabetes, reduced birthweight, reduced semen quality, polycystic ovarian syndrome, endometriosis, and breast cancer. Evidence also exists for relations between bisphenols and adult diabetes, reduced semen quality, and polycystic ovarian syndrome; phthalates and prematurity, reduced anogenital distance in boys, childhood obesity, and impaired glucose tolerance; organophosphate pesticides and reduced semen quality; and occupational exposure to pesticides and prostate cancer. Greater evidence has accumulated than was previously identified for cognitive deficits and attention-deficit disorder in children following prenatal exposure to bisphenol A, organophosphate pesticides, and polybrominated flame retardants. Although systematic evaluation is needed of the probability and strength of these exposure–outcome relations, the growing evidence supports urgent action to reduce exposure to EDCs.
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Endocrine-disrupting chemicals: economic, regulatory, and policy implications
Endocrine-disrupting chemicals (EDCs) substantially cost society as a result of increases in disease and disability but—unlike other toxicant classes such as carcinogens—have yet to be codified into regulations as a hazard category. This Series paper examines economic, regulatory, and policy approaches to limit human EDC exposures and describes potential improvements. In the EU, general principles for EDCs call for minimisation of human exposure, identification as substances of very high concern, and ban on use in pesticides. In the USA, screening and testing programmes are focused on oestrogenic EDCs exclusively, and regulation is strictly risk-based. Minimisation of human exposure is unlikely without a clear overarching definition for EDCs and relevant pre-marketing test requirements. We call for a multifaceted international programme (eg, modelled on the International Agency for Research in Cancer) to address the effects of EDCs on human health—an approach that would proactively identify hazards for subsequent regulation.
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