Menopausal Transition - A Window of Susceptibility for the Promotion of Breast Cancer by Environmental Exposures
Location(s): United States
The goal of this application is to determine the effects of environmental exposures on the development of breast cancer during the menopausal transition, a period when 30% of breast cancers are diagnosed. The breast cancer promoting effects of two types of environmental chemicals, bisphenol A (BPA) and polybrominated diphenyl ethers (PBDEs; a class of persistent organic pollutants) will be investigated by a transdisciplinary approach integrating in vitro cell line experiments, in vivo mouse models, and a population-based study of women during the menopausal transition. We expect this work to ultimately result in future prevention strategies to reduce or mitigate exposures in order to reduce the incidence of breast cancer.
In Specific Aim 1, we will determine the biologic actions and mechanisms of EDCs, singly and in combination, using the AroER-Tri screen cell culture system developed by the joint-Principal Investigator, Dr. Chen.
In Specific Aim 2, we will assess the effects of EDCs in women during the menopausal transition on estrogenic activity and the epigenome, as well as the association of the EDCs and breast cancer.
In Specific Aim 3, we will test the effects of these EDCs on the development of mammary lesions in a mouse model of menopause, and compare to the effects in an ovarectomized mouse model. Our transdisciplinary approach will capitalize on the strengths of each study type and allow us to conduct a more comprehensive assessment than any single approach. This is possible because of our experienced, multidisciplinary team.
In Specific Aim 4, with our community partners, we will provide a one-stop web-based resource for evidence-based materials on the role of environmental exposures and development of breast cancer, particularly during the menopausal transition. Furthermore, we will develop, test, and disseminate educational materials to multi-culturally diverse communities. We will share our expertise/work with other multi-disciplinary teams in the BCERP to produce valuable results and increase the amount of relevant scientific knowledge on the mechanisms and effects of EDC exposure. We expect this work to result in future prevention strategies to reduce or mitigate exposures and promote effective communication of scientifically sound findings to the general public and policy makers.