Abstract A63: The impact of psychosocial stress on pubertal mammary gland development in a rat model of spontaneous breast cancer

Social stressors cause reproducible changes in neuroendocrine physiology and can thereby disrupt developmental processes leading to increased susceptibility to disease later in life. Social circumstances that manifest as psychological stressors place individuals at a distinct disadvantage in health and disease. Recent research has highlighted that a myriad of psychosocial and environmental stressors, including those that are common in the medically underserved (e.g. social marginalization and isolation, economic uncertainty, and racism), can result in changes in cellular gene expression and phenotype. Less is known about the specific physiological, cellular and molecular pathways that mediate deviations that result from psychosocial stress, particularly from a developmental perspective when the risk factors are set in motion. We expect that these pathways will be tissue and disease specific. Therefore, we have chosen to focus specifically on breast cancer and use an animal model, Sprague-Dawley rats, where there is an established effect of social marginalization/isolation on mammary gland development and increased mammary cancer risk. When exposed to post-weaning social isolation, a well-characterized psychosocial stressor, Sprague-Dawley rats exhibit more invasive tumors than their group-housed counterparts and a greater overall tumor burden. The shift toward malignancy in social isolates is also associated with changes in pubertal mammary gland development. Because the mammary gland is particularly susceptible to environmental stressors during development, we hypothesized that puberty is a critical developmental window during which social isolation can increase the risk of mammary gland tumor burden later in life. To this end, we isolated or group-housed female pubertal rats and characterized ductal development in a variety of ways. To determine gross morphology, we analyzed the architecture of mammary gland whole mounts. During early puberty, animals exposed to psychosocial stressors showed a decrease in terminal end buds, structures involved in ductal extension. These early changes correlated with decreased ductal extension in the social isolates later in puberty. To investigate the possible impact of the mammary microenvironment on cell proliferation in ductal extension, we made media conditioned with the mammary adipose tissue from group or isolated rats and tested its relative ability to drive mammary epithelial cell proliferation. These results indicate a potential relationship between exposure to psychosocial stressors and disruption of pubertal mammary gland development, which may increase cancer risk. Citation Format: Marianna Johnson, Joscelyn N. Hoffmann, Hannah You, Kyle Kunze, Sully Fernandez, Matthew Brady, Martha McClintock, Suzanne Conzen. The impact of psychosocial stress on pubertal mammary gland development in a rat model of spontaneous breast cancer. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr A63.