Preclinical Models to Study Obesity and Breast Cancer in Females: Considerations, Caveats, and Tools

J Mammary Gland Biol Neoplasia. 2020 Dec;25(4):237-253. doi: 10.1007/s10911-020-09463-2. Epub 2020 Nov 4.

Abstract

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.

Keywords: Adipose tissue; Breast cancer; Carcinogen; Diet; Menopause; Obesity; Ovariectomy; Preclinical model; Thermoneutrality; Tumor subtype.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adiposity / physiology
  • Animals
  • Breast / pathology*
  • Breast Neoplasms / etiology*
  • Breast Neoplasms / pathology
  • Breast Neoplasms / physiopathology
  • Carcinogenesis / chemically induced
  • Carcinogenesis / pathology
  • Carcinogens / administration & dosage
  • Carcinogens / toxicity
  • Cell Line, Tumor
  • Diet, High-Fat / adverse effects
  • Dietary Sugars / administration & dosage
  • Dietary Sugars / adverse effects
  • Female
  • Humans
  • Mammary Glands, Animal / drug effects
  • Mammary Glands, Animal / pathology*
  • Mammary Neoplasms, Experimental / etiology
  • Mammary Neoplasms, Experimental / pathology*
  • Mammary Neoplasms, Experimental / physiopathology
  • Menopause / physiology
  • Mice
  • Mice, Transgenic
  • Obesity / complications*
  • Obesity / pathology
  • Obesity / physiopathology
  • Rats
  • Xenograft Model Antitumor Assays

Substances

  • Carcinogens
  • Dietary Sugars