乳腺癌(BC)的发生与雌激素密切相关。随着环境污染加剧，多溴联苯醚(PBDEs)等环境雌激素(EEs)在人群中的暴露水平持续升高。PBDEs是否影响BC的发生、发展及其内分泌治疗敏感性，目前尚无报道。本课题将开展大样本的病例对照研究，探索PBDEs暴露与BC发生风险的关系，及与其内分泌治疗耐受的相关性。机制方面，已证实某些EEs主要通过与ERα/β或G蛋白偶联受体30(GPR30)结合发挥生物学效应，尤其与GPR30的亲和力较ERα/β高，其中GPR30-EGFR-ERK是一条参与BC细胞侵袭和转移的重要信号通路。PBDEs是否通过上述受体途径和信号通路影响BC的增殖、迁移和内分泌治疗耐受，值得探索。本研究将通过系列体外和体内实验，探索PBDEs在BC发生、发展及内分泌治疗耐受中的可能作用及相关机制，为研究PBDEs与激素相关肿瘤的关系提供理论依据，同时为BC内分泌治疗抵抗研究提供新思路。

The occurrence of breast cancer is closely related to estrogens. The role of environmental estrogens (EEs) played in the development of breast cancer has gotten elevated concern in recent years. EEs also as xenoestrogens, environmental hormones, or estrogen-like chemicals, are the chemicals with the capacity of imitating estrogen, by binding to classical estrogen receptors (ERs) such as ERα/β or G-protein-coupled receptor 30 (GPR30), and activating ER signaling pathways. As the environmental pollution is aggravating, EEs such as polybrominated diphenyl ethers (PBDEs) exposure levels continue to rise in the population. It is reported that some EEs can cause many reproduction and developmental problems and different kinds of cancers, and studies over the last decades have helped people to believe that the exposure of these compounds can affect the occurrence and/or development of breast cancer, but evidences about the associations were not enough or the results turned out to be inconsistent. Whether PBDEs may affect the occurrence and development of breast cancer, and whether they maybe affect the endocrine therapy tolerance of breast cancer is still unclear, as well as the mechanism is. This project will carry out case-control studies with large sample size, to explore the relationships between PBDEs exposure and breast cancer risk; and association with the resistance of endocrine therapy. To the mechanism aspect, in the recent years scientists found that GPR30-EGFR-ERK might be one of the important signaling pathways to the proliferation and invasion of breast cancer cells. As a new type of membranous estrogen receptor,GPR30 is independent of ERα/β, which mediates the rapid response and transcriptional regulation of estrogen-like substance through the activation of epidermal growth factor receptor (EGFR) and second messenger system, to participate in a variety of diseases and tumor biological processes. EEs such as PBDEs have the higher affinity with GPR30 than ER α,β, and bring forth estrogen effect. Therefore, whether PBDEs can influence the occurrence and development of breast cancer,and endocrine therapy resistance of breast cancer through this signal pathway is worth to explore. We will perform in vitro and in vivo experiments, to study the impact of GPR30-EGFR-ERK pathway in the role of breast cancer cell proliferation and invasion, and endocrine therapy resistance influenced by PBDEs exposure. Through this study, we aim to preliminary clarify the associations between PBDEs exposure and the risk of getting breast cancer, and lay the foundation for other environmental estrogens research.