Impact of Obesity on Breast Cancer Recurrence and Minimal Residual Disease. Mus musculus

To determine whether the obese phenotype could be generated in MTB/TAN mice on a FVB/N background, 3 week old female mice were randomized to a high fat diet (HFD), consisting of 60% calories from fat – comparable to the percentage fat content of certain human fast food options, or a matched control low fat diet (LFD), comprising 10% calories from fat, in the context of a recurrence assay. In brief, doxycycline was provided to HFD- and LFD-fed mice to drive oncogene-dependent primary breast tumorigenesis, following which tumor regression was induced by doxycycline withdrawal. Obese and non-obese mice were then monitored for tumor recurrence to determine the impact of obesity. Notably, genetically identical mice had varying responses to HFD. In order to define obesity in an analogous manner as in humans, mice that experienced a 20% increase in body weight relative to age-matched LFD at time of enrollment into the recurrence assay were defined as “HFD-Obese”, which corresponded with the weight increase for an average height U.S. female to move from a BMI of 24.9 (normal) to a BMI of 30 (obese). HFD-Obese mice weighed significantly more than LFD and HFD-Lean mice at enrollment, which persisted at study end. Increased body weight corresponded to greater fat mass, including a 22% absolute increase in body fat percentage between HFD-Obese and LFD mice at time of enrollment, which parallels the 15% absolute difference in body fat percentage between lean (BMI <25 kg/m2) and obese (≥30 kg/m2)