Researchers conducted a study that analyzed published research examining the genotoxicity of potentially carcinogenic chemicals and their role in breast cancer, as well as the activation of progesterone or estradiol signaling.
The objective of the research was to identify chemicals that could pose a breast cancer risk for humans.
Recent statistics show that breast cancer is the most common type of cancer and the leading cause of cancer-related mortality among women worldwide. In the United States (USA), the lifetime risk of developing breast cancer is double that of developing lung cancer.
Additionally, the incidence of breast cancer in younger women is increasing, with the mortality rate from breast cancer in women aged 20-49 years being twice as high as other cancers affecting both genders.
A nine-year survey since 2010 also shows that the diagnosis rate of breast cancer in women under 40 has increased by 1.1% each year.
One potentially effective approach to reducing breast cancer risk is to identify potentially carcinogenic or breast tumor-promoting chemicals that can cause endocrine disruption or genotoxicity and take informed measures to reduce exposure to such chemicals.
Using animal models such as rodents with similar tissue structures, genotoxicity, and humoral signaling pathways involved in breast tumors, similar to those in humans, can help identify chemicals that could potentially be carcinogens in humans.
About the Study
In the study, the researchers used databases such as monographs from the International Agency for Research on Cancer (IARC) and the US Environmental Protection Agency’s ToxCast to identify chemicals that are known to induce breast tumors and stimulate the synthesis of progesterone or estradiol and activate estrogen receptors in in vitro experiments.
These chemicals were classified based on key characteristics such as genotoxicity and the strength of endocrine activity, and these key characteristics were assessed for their ability to predict the breast tumor-inducing activity of these chemicals.
The IARC has developed a list of key characteristics for known human carcinogens to document their biological effects and provide a framework for identifying other chemicals that could potentially be carcinogenic.
Documented key characteristics include genotoxicity, increased cell proliferation, changes in cell signaling, inflammation, epigenetic changes, and immunosuppression. The presence of one or more of these key characteristics suggests potential carcinogenic effects.
While genotoxicity and the ability to alter DNA or influence DNA repair mechanisms are the two most important key characteristics for most carcinogens, hormone receptor activity and endocrine signaling are important key characteristics when considering breast cancer.
The role of progesterone and estrogen receptors is important for understanding breast cancer risk and developing treatment options.
The chemicals studied in this study were classified based on breast cancer-relevant exposures according to their endocrine activity and genotoxicity, and an existing list of breast carcinogens from 2007 was updated to include chemicals that activate breast cancer-relevant endocrine pathways.
The proportion of breast carcinogens demonstrating biological effects, such as the activation of breast cancer-relevant endocrine signaling pathways, was also calculated as a proportion of all chemicals examined in the study.
The results identified 279 breast carcinogens and 642 other chemicals with the main property of stimulating progesterone or estrogen signaling, comprising a total list of 921 breast cancer-relevant exposures.
Furthermore, other key characteristics such as genotoxicity, estrogen receptor agonism, and steroidogenesis were enriched in these breast carcinogens, indicating that key characteristics were an effective method for predicting whether a chemical is capable of inducing breast tumors in rodents and, more broadly, of posing a breast cancer risk to humans.
Among the observed key characteristics, steroidogenesis was more common in breast carcinogens than estrogen receptor agonism, with most of them increasing the secretion of progesterone and estradiol.
The researchers believed that, given the identification of numerous additional chemicals showing important breast cancer risk characteristics, it is important to develop better assessment methods and improved tests to evaluate the ability of chemicals to induce breast tumors and reduce exposure.
In summary, this study identified a total of 921 breast carcinogens or chemicals in rodents that can induce breast tumors, and thus could pose a breast cancer risk to humans.
The results underscore the importance of using the framework of key characteristics in identifying potential breast cancer agents.
- Kay JE, Brody JG, Megan S, et al. (2024). Application of the Key Characteristics Framework for Identifying Potential Breast Carcinogens Using Publicly Available In Vivo, In Vitro, and In Silico Data. Environmental Health Perspectives 132(1), 017002. doi: 10.1289/EHP13233. https://ehp.niehs.nih.gov/doi/10.1289/EHP13233