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Breast Cancer Research
Published in: Breast Cancer Research 1/2022

Open Access 01-12-2022 | Obesity | Research article

Preventing ovariectomy-induced weight gain decreases tumor burden in rodent models of obesity and postmenopausal breast cancer

Authors: Elizabeth A. Wellberg, Karen A. Corleto, L. Allyson Checkley, Sonali Jindal, Ginger Johnson, Janine A. Higgins, Sarina Obeid, Steven M. Anderson, Ann D. Thor, Pepper J. Schedin, Paul S. MacLean, Erin D. Giles

Published in: Breast Cancer Research | Issue 1/2022

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Abstract

Background

Obesity and adult weight gain are linked to increased breast cancer risk and poorer clinical outcomes in postmenopausal women, particularly for hormone-dependent tumors. Menopause is a time when significant weight gain occurs in many women, and clinical and preclinical studies have identified menopause (or ovariectomy) as a period of vulnerability for breast cancer development and promotion.

Methods

We hypothesized that preventing weight gain after ovariectomy (OVX) may be sufficient to prevent the formation of new tumors and decrease growth of existing mammary tumors. We tested this hypothesis in a rat model of obesity and carcinogen-induced postmenopausal mammary cancer and validated our findings in a murine xenograft model with implanted human tumors.

Results

In both models, preventing weight gain after OVX significantly decreased obesity-associated tumor development and growth. Importantly, we did not induce weight loss in these animals, but simply prevented weight gain. In both lean and obese rats, preventing weight gain reduced visceral fat accumulation and associated insulin resistance. Similarly, the intervention decreased circulating tumor-promoting growth factors and inflammatory cytokines (i.e., BDNF, TNFα, FGF-2), with greater effects in obese compared to lean rats. In obese rats, preventing weight gain decreased adipocyte size, adipose tissue macrophage infiltration, reduced expression of the tumor-promoting growth factor FGF-1 in mammary adipose, and reduced phosphorylated FGFR indicating reduced FGF signaling in tumors.

Conclusions

Together, these findings suggest that the underlying mechanisms associated with the anti-tumor effects of weight maintenance are multi-factorial, and that weight maintenance during the peri-/postmenopausal period may be a viable strategy for reducing obesity-associated breast cancer risk and progression in women.
Appendix
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Metadata
Title
Preventing ovariectomy-induced weight gain decreases tumor burden in rodent models of obesity and postmenopausal breast cancer
Authors
Elizabeth A. Wellberg
Karen A. Corleto
L. Allyson Checkley
Sonali Jindal
Ginger Johnson
Janine A. Higgins
Sarina Obeid
Steven M. Anderson
Ann D. Thor
Pepper J. Schedin
Paul S. MacLean
Erin D. Giles
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2022
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-022-01535-x

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