Obesity increases the risk for breast cancer and is associated with poor outcomes for cancer patients. A variety of rodent models have been used to investigate these relationships; however, key differences in experimental approaches, as well as unique aspects of rodent physiology lead to variability in how these valuable models are implemented. We combine expertise in the development and implementation of preclinical models of obesity and breast cancer to disseminate effective practices for studies that integrate these fields. In this review, we share, based on our experience, key considerations for model selection, highlighting important technical nuances and tips for use of preclinical models in studies that integrate obesity with breast cancer risk and progression. We describe relevant mouse and rat paradigms, specifically highlighting differences in breast tumor subtypes, estrogen production, and strategies to manipulate hormone levels. We also outline options for diet composition and housing environments to promote obesity in female rodents. While we have applied our experience to understanding obesity-associated breast cancer, the experimental variables we incorporate have relevance to multiple fields that investigate women’s health.
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The data generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
Human epidermal growth factor receptor 2
Body mass index
Patient derived xenograft
Mouse mammary tumor virus
Whey acidic promoter
Polyoma-virus middle T antigen
Mouse-derived syngeneic transplant
NOD-SCID (non-obese diabetic, severe combined immunodeficient) IL2R-gamma
Peripheral blood mononuclear cell
Dual-energy x-ray absorptiometry
High fat/high sucrose
Low fat/high sucrose
Low fat/low sucrose
Homeostatic model assessment of insulin resistance
Quantitative magnetic resonance
National Health and Nutrition Examination Survey
Peripheral blood mononuclear cell
Standard error of the mean
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Development of these models was a team effort, and we are incredibly grateful to the members of the ‘Fat Rat’ team, who were instrumental in developing and characterizing these models. This includes: Drs. Paul MacLean, Pepper Schedin, Ann Thor, Steven Anderson, and members of each of their labs. We are equally grateful to the skilled research technicians who ensured the success of the many studies in mice and rats that contributed to this work. Summary figures were created using BioRender.com.
This work was supported by the NIH R00CA169430 (Giles), R01CA241156 (Wellberg), R01CA164166 (MacLean), Colorado Nutrition Obesity Research Center Metabolic Phenotyping Core and Pilot Grant Program P30DK48520, TREC Training Workshop R25CA203650 (Giles and Wellberg), KL2TR002534 (Wellberg), the Komen Foundation CCR17483321 (Wellberg), and seed grants from the University of Colorado’s Center for Women’s Health Research (Giles and Wellberg).
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All animal work was approved by Texas A&M and/or University of Colorado Institutional Animal Care and Use Committees.
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Giles, E.D., Wellberg, E.A. Preclinical Models to Study Obesity and Breast Cancer in Females: Considerations, Caveats, and Tools. J Mammary Gland Biol Neoplasia 25, 237–253 (2020). https://doi.org/10.1007/s10911-020-09463-2