Abstract 4455: Mild and moderate early-life stressors differentially affect stress reactivity and mammary tumorigenesis in BALB/c mice: A new look at the stress and breast cancer relationship

Many studies have produced inconsistent support for the hypothesized role of stressful life events in breast cancer risk. One major factor contributing to the inconsistent data could be that differences in premorbid physiological (e.g., endocrine levels) and psychological (e.g., emotional reactivity to challenges) characteristics were not taken into account and therefore, nor was the enduring impact of these differences on many aspects of endocrine activity and mammary gland development. It is difficult to gain information on human childhood variables that affect breast development and even more still on the influence of those variables into adulthood. Thus, evidence for factors influencing breast development and increased cancer risk during this time is limited. To this end, we use an established rodent model in which mild and moderate chronic neonatal stressors of brief and long maternal separation (BMS and LMS, respectively) over the first 3 weeks of life cause enduring functional changes to limbic-pituitary-adrenal axis activity. With this model, we show that BMS and LMS experiences differentially alter emotion- and stress-related behaviors of adult female BALB/c offspring. Circulating, corticosterone (CORT) and estrogen (E2) levels were also differentially altered by the BMS and LMS experiences as were transcript or protein levels of estrogen receptor (ER)α and ERα in ‘normal’ mammary glands. Interestingly, increased mammary tumorigenesis in LMS mice following adulthood carcinogen (7,12-dimethylbenz[α]anthracene; DMBA) administration was related to lower circulating plasma CORT and E2 levels, higher ERα protein (but not transcript), and lower ERα transcript (but not protein) levels in mammary glands. We suggest that early-life physical and psychosocial environments influence breast cancer risk by shaping the behavioral phenotype and altering circulating hormone levels which in turn alter the cellular and molecular architecture of the breast predisposing some to increased risk of carcinogenesis. A better understanding of the biobehavioral pathways that govern the complex interplay among environment, phenotype, and normal and malignant breast development will facilitate the creation of effective behavioral and cellular strategies for cancer prevention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AAC