Sporadic breast cancer is a hormone dependent malignancy with a steadily increasing incidence. Although the reasons for this increase are uncertain, epidemiologic findings support an important role for environmental pollutants containing endocrine disrupting chemicals (EDCs) and their metabolites. The last six decades have witnessed a massive introduction of hormonally active synthetic chemicals into the environment. Therefore, exposure to EDCs at critical windows of opportunity during the life course may play a role in changing the susceptibility to breast carcinogenesis. Herein, we propose to explore whether exposure to three environmental compounds with different endocrine-disrupting pathways, butyl perfluorooctanoic acid (PFOA), benzyl phthalate (BBP), and Zeranol during the pubertal period will alter breast composition and/or the susceptibility to breast cancer. We will build on an existing puberty cohort of in 400 Latino girls in Chile for whom breast composition measurements at Tanner stage 4 are already available. We propose to extend this cohort to add a breast composition assessment two years after menarche as breast density tracks from this point into adulthood. We propose to study the influence of the three chemicals, PFOA, BBP, and Zeranol, individually and in combination, on breast composition in these Latino girls. To explore whether pubertal exposure to PFOA, BBP, and Zeranol has deleterious effects on mammary gland biology and susceptibility to carcinogenesis, we will study the morphology, transcriptome, and tumorigenesis of the rat mammary gland exposed to these compounds. Results from our work will be disseminated via community outreach to family members of study participants and community members in Chile. Furthermore, we will connect this project and BCERP with breast cancer advocacy in the United States, creating opportunities for translation into personal and policy change to promote health.
In this application, we are aiming to understand the biological and molecular mechanisms of pubertal exposure to butyl benzyl phthalate (BBP), perfluorooctanoic acid (PFOA), and Zeranol alone or in combination on breast composition and the susceptibility to breast cancer. To accomplish these aims, we pair animal experiments with observational studies in a puberty cohort of Latino girls. Our findings will be disseminated via community outreach in both the United States and Chile.
| Binder, Alexandra M; Corvalan, Camila; Pereira, Ana et al. (2018) Prepubertal and Pubertal Endocrine-Disrupting Chemical Exposure and Breast Density among Chilean Adolescents. Cancer Epidemiol Biomarkers Prev 27:1491-1499 |
| Binder, Alexandra M; Stiemsma, Leah T; Keller, Kristen et al. (2018) Inverse association between estrogen receptor-? DNA methylation and breast composition in adolescent Chilean girls. Clin Epigenetics 10:122 |
| Binder, Alexandra M; Corvalan, Camila; Mericq, Verónica et al. (2018) Faster ticking rate of the epigenetic clock is associated with faster pubertal development in girls. Epigenetics 13:85-94 |
