“We know that there are over a dozen cancers that are associated with obesity and breast cancer is one of them.
The increased risk for cancer associated with obesity is mediated partly by changes in the immune system. Hypertrophic adipocytes undergo phenotypic changes and begin to secrete inflammatory adipokines (bioactive molecules released from an adipocyte) and cytokines (immune signaling molecules involved in inflammation, immunity, and cell communication).
These act locally and systemically to induce persistent, low-grade inflammation that fails to resolve.
Obesity-associated adipose tissue thus functions as an inflammatory endocrine organ, particularly in visceral tissue producing TNF-α, IL-6, IL-1β, Monocyte chemoattractant Protein 1 (MCP-1, which is associated with tamoxifen resistance), and leptin while reducing adiponectin (an anti-inflammatory adipokine) levels, thereby promoting chronic low-grade inflammation, insulin resistance, and tumor-promoting signaling pathways.
This increases cancer risk by two distinct mechanisms – both through the promotion of chronic inflammation, and through inhibition of the acute inflammation that is important to halt tumorigenesis (anti-tumor immunity). GLP-1 analogs both increase adiponectin expression and reduce adipose-associated inflammation, including reductions in TNF-α, IL-6, and leptin.
Additionally, in the case of breast cancer, fat cells produce estrogen and the majority of breast cancers express estrogen receptors and grow in response to estrogen. So maintaining a healthy weight in peri-menopause and menopause is important.
GLP-1 agonists, through weight loss dependent mechanisms, reduce estrogen and inflammation. They also have metabolic effects and help decrease insulin resistance.
While it is plausible biologically and supported by clinical trials that weight loss alone would decrease breast cancer risk, GLP-1 agonists are likely working through other pathways.
We do not yet know whether they directly affect tumor growth and development independent of weight loss benefits, or if and how they impact the metabolic activity of tumors or influence inflammation within the tumor microenvironment.”
— Elizabeth McDonald, MD, PhD
