Psychosocial stress exposure results in inhibition of mammary gland development and increased mammary stem cells in a rat model of breast cancer

Exposure to unremitting psychosocial stressors common to underserved populations (i.e., social marginalization and isolation, economic uncertainty, and racism) manifest in physiologic changes that are associated with highly aggressive mammary cancer. Many environmental exposures that influence breast cancer risk in adulthood occur earlier in life during the time of mammary gland development. However, the effect of stress physiology on mammary gland development and its link to breast cancer remains unknown. In a model of psychosocial stress (social isolation), we studied whether a social isolation-induced stress response would affect mammary gland development. To this end, we used the Sprague Dawley rat, where there is an established effect of psychosocial stress on increasing later-life mammary cancer risk. Here, we found that post-weaning social isolation was associated with decreased ductal differentiation and increased mammary stem cells (MaSC). Using an in vitro model, we next determined if glucocorticoid receptor activation increased MaSC survival through direct and paracrine mechanisms. Our findings provide evidence that social stressors induce glucocorticoid exposure and decrease mammary gland differentiation leading to an increased MaSC population, potentially contributing to a greater mammary cancer risk. Citation Format: Marianna B. Johnson, Joscelyn N. Hoffmann, Hannah M. You, Ahmad B. Allaw, Jordan W. Strober, Matthew J. Brady, Martha K. McClintock, Suzanne D. Conzen. Psychosocial stress exposure results in inhibition of mammary gland development and increased mammary stem cells in a rat model of breast cancer [abstract]. In: Proceedings of the Tenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2017 Sep 25-28; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2018;27(7 Suppl):Abstract nr B53.