Abstract 24: The effect of chronic psychological stress during puberty and early adulthood on mammary gland development and mammary cancer risk in adulthood

Abstract

Abstract Breast cancer is the second most common cancer among women in the United States. Puberty is a well-established sensitive period in women when breast cancer (BC) risk is increased by the physical environment for example exposure to chemical carcinogens, synthetic estrogens, endocrine disrupters, radiation, etc. However, relatively little is known about effects of exposure to chronic psychological stress from the social environment during this time period (puberty and early adulthood). In previous studies using the Sprague-Dawley rat model of spontaneous mammary cancer, chronically heightened glucocorticoid stress reactivity arising from imposed social isolation after weaning increased duration of glucocorticoid release in response to everyday stressors, impeded mammary gland ductal development, and caused earlier and more aggressive mammary gland cancer incidence during adulthood. However due to the period of isolation lasting from weaning to death, a critical time period in which these changes occurred was not established. Here we found that chronic social isolation only during puberty and early adulthood results in alterations in mammary gland gene expression patterns and preservation of mammary stem/progenitor cells. We have observed that social isolation beginning at five weeks and ending at 21 weeks leads to a 4-fold increase in the key metabolic lipogenic enzymes ATP citrate lyase (ACLY; p-value = 0.008), 2-fold increase in acetyl-CoA carboxylase (Acaca; p-value=0.01), and 1.88-fold change in stearoyl-CoA desaturase 1 (Scd1; p-value = 0.50). Interestingly, we have also observed that social isolation during this time period, leads to a slight decrease (0.70-fold change) in hexokinase 2 (HK2; p-value= 0.007). Regarding mammary stem/progenitor cell preservation, we found that social isolation beginning at five weeks and ending at 17 weeks leads to a significant increase in the number of mammary gland stem/progenitor cells (isolated by FACS sorting). This correlation was only observed in response to corticosterone reactivity, and null to exposure to estrogen or progesterone. In summary, our findings suggest that social isolation during puberty and early adulthood correlates to increased glucocorticoid exposure resulting in metabolic reprogramming in the mammary gland and inappropriate preservation of mammary stem/progenitor cells. Altogether these factors may increase the risk of mammary cancer occurrence later in adulthood. Citation Format: Briana Banks, Marianna Johnson, Joscelyn Hoffmann, Hannah You, Matt Piron, Suzanne Conzen, Martha McClintock, Matthew Brady. The effect of chronic psychological stress during puberty and early adulthood on mammary gland development and mammary cancer risk in adulthood [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 24.