Abstract 1982: Obesity reversibly enhances mammary epithelial estrogen receptor alpha expression and progenitor activity

Abstract

Listen

Translate article

Abstract Obesity has been identified as an important risk factor for breast cancer in post-menopausal women and is significantly correlated with poor prognosis in breast cancer patients. Women with an increasing body mass index (BMI) are more likely to develop estrogen receptor alpha (ERα) positive tumors that are larger at the time of diagnosis and demonstrate an increased risk for metastasis. Given that obesity is becoming a global epidemic, understanding how obesity alters the biology of the normal breast is of significant clinical relevance. To examine the effects of obesity on mammary tissue, mice were fed a high fat diet to induce obesity and compared with mice fed a control diet. We also examined reduction mammoplasty tissue from women with a known BMI. In both obese female mice and women, mammary epithelial cell populations demonstrated significant decreases in basal/myoepithelial cells, when examined using either flow cytometry or cell type-specific markers (SMA and p63) in tissue. ERα expression was significantly increased in luminal cells in obese mammary tissue, compared with control mice or breast tissue from lean women. Functional assays demonstrated significantly enhanced mammary epithelial progenitor activity in obese mammary epithelial cells as well as elevated numbers of ERα positive epithelial cells that were co-labeled with markers of proliferation. Weight loss in a group of obese mice reversed increases in progenitor activity and ERα expression observed in obese mammary tissue. Obesity enhances the percentage of ERα positive epithelial cells and reduces the number of basal/myoepithelial cells within normal mammary tissue in both women and female mice. Both aspects of this phenotype have been linked to breast tumor susceptibility. These changes may contribute to lifetime risk for the development of ERα positive tumors in postmenopausal women. However, the changes in epithelial cell populations induced by obesity are reversible with weight loss, suggesting that weight loss interventions in obese women may effectively reduce breast cancer risk by decreasing the number of potential tumor progenitor cells in the breast epithelium. Citation Format: Tamara Chamberlin, Joseph V. D'Amato, Lisa M. Arendt. Obesity reversibly enhances mammary epithelial estrogen receptor alpha expression and progenitor activity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1982.