Menopausal Transition: A Window of Susceptibility for the Promotion of Breast Cancer by Environmental Exposures
Breast Cancer & the Environment Research Program
Beckman Research Institute of the City of Hope
NIEHS Grant: U01ES026137
Other Community and Academic Partners:
Breast Cancer Care and Research Fund
City of Hope's Center of Community Alliance for Research and Education
There is substantial evidence suggesting that environmental disrupting chemicals (EDCs) initiate and promote the development of breast cancer. In this project, researchers are studying an under-investigated window of susceptibility for exposure: the menopausal transition. This transition begins when ovarian function begins to decline and ends at menopause when there is a cessation of ovarian function resulting in low levels of estrogens. During this important window of susceptibility, the Women's Health Initiative (WHI) reported that hormone therapy increased both the incidence of and mortality from breast cancer. The WHI results are explained by a biologically-based breast tumor model; it suggests that hormone therapy in the menopausal transition promotes the growth of pre-existing occult lesions and minimally initiated de novo tumors.
The research team is investigating the hypothesis that EDCs mimic hormone therapy and promote the development of breast cancer during the menopausal transition. They are focusing on polybrominated diphenyl ethers (PBDEs) because of their persistence in the environment and human tissue and on bisphenol A (BPA) because of its widespread use in food-grade plastics and thermal paper. Both EDCs are recognized as major health concerns. Their research allows us to evaluate the role of these EDCs, individually and combined, on the development of breast cancer during the menopausal transition. To determine the mechanisms, they are applying a transdisciplinary approach using cell culture, samples collected from women during the menopausal transition, and mouse models.
The researchers aim to:
- 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.
- 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.
- 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.
This transdisciplinary approach capitalizes on the strengths of each study type and allows the researchers to conduct a more comprehensive assessment than any single approach. This is possible because of their experienced, multidisciplinary team.
With community partners, the team is providing 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, they are developing, testing, and disseminating educational materials to multi-culturally diverse communities. They also will share their expertise/work with other multidisciplinary teams in the BCERP to produce valuable results and increase the amount of relevant scientific knowledge on the mechanisms and effects of EDC exposure.