Intermittent fasting modulates breast cancer pathogenesis Nikita Thakkar1,2, Kafi Ealey1, Ju Hee Lee1,2, Min Choe1, Christy Yeung1,2, Navkiran Verma1,2, Mehr Rakhshani1,2, Hoon-Ki Sung1,2 1 Translational Medicine Program, The Hospital for Sick Children 2 Department of Laboratory Medicine and Pathobiology, University of Toronto Toronto, ON, Canada Obesity is a known risk factor for the development of breast cancer and prognosis. As adipose tissue (AT) constitutes a major component of the breast tissue microenvironment, obesity driven AT inflammation and fibrosis (fibro-inflammation) is tightly associated with breast cancer pathogenesis and treatment outcomes. Intermittent Fasting (IF) is an effective dietary intervention characterized by periodic energy restriction and has been used to improve whole-body metabolism and combat obesity. Since our previous studies have shown IF to decrease AT inflammation, we postulate that IF may modulate breast cancer pathogenesis. Our current study aims to investigate the impact of IF on mammary tumor onset, progression, and metastasis as well as the regimens therapeutic potential. Using spontaneous mammary tumor developing model, polyomavirus middle T antigen (MMTV-PyMT), we conducted IF consisting of 2 days of feeding followed by 1 day of fasting on females. Tumor stromal cell analysis shows that fasting is able to regulate the characteristics of the tumor immune cell phenotype. Taken together, our study provides a novel insight on IF as an intervention for adipose-rich breast cancer development and progression through the modulation of tumor microenvironment. A tangible and comprehensive approach such as IF is an attractive intervention to mitigate breast cancer pathogenesis and to improve treatment outcome.