Insulin resistance increases breast cancer aggressiveness

Insulin resistance makes breast cancer more aggressive and promotes brain metastasis.

Metabolic conditions like type 2 diabetes and pre-diabetes foster a pro-metastatic tumor microenvironment, reducing survival. Patients should always be monitored for this and appropriate metabolic interventions made part of the treatment plan.

A research article just published in Molecular Cancer Research explores how insulin resistance of adipose tissue drives worse outcomes for breast cancer. The authors state:

“Patients with triple negative breast cancer (TNBC) and comorbid Type 2 Diabetes (T2D), characterized by insulin resistance of adipose tissue, have higher risk of metastasis and shorter survival.”

They further note:

“Adipocytes are the main non-malignant cells of the breast tumor microenvironment (TME). However, adipocyte metabolism is usually ignored in oncology…”

Spread via Exosomes

Exosomes are tiny vesicles formed inside cells that contain cellular proteins, DNA, and RNA. They get released into the blood by cells, including cancer cells, and travel to other parts of the body where they can transfer the proteins, DNA, and RNA they contain into other cells. This is how they promote the spread of cancer and can also keep immune cells from killing cancer cells.*

The authors set out to investigate how exosomes secreted by the TME breast adipocytes might drive epithelial-to-mesenchymal transition (EMT) [malignant transformation] and metastasis in TNBC via miRNAs. It’s difficult to over emphasize the importance of their results:

“EMT, proliferation and angiogenesis [growth of tumor-feeding blood vessels] were elevated in IR [insulin resistant] vs. control and IS [insulin sensitive].”

Moreover:

“Brain metastases showed more mesenchymal morphology and EMT enrichment in the IR group. MiR- 145a-3p is highly differentially expressed between IS and IR, and potentially regulates metastasis.”

Implications

Highlighting their conclusions, they emphasize:

“IR [insulin resistant] adipocyte exosomes modify the TME, enhance EMT, and promote brain metastasis—likely via miRNA pathways—suggesting that metabolic diseases like T2D foster a pro-metastatic TME, reducing survival, warranting close monitoring and potential metabolic interventions in TNBC patients with T2D.”

It is crucially important for providers to be aware that clinically significant insulin resistance is a major factor prior to worsening to the point of crossing the line into type 2 diabetes, and that this pertains to other cancers as well as breast cancer. For more on this see The Triglyceride–Glucose Index is a powerful biomarker for cardiovascular disease, depression, dementia, cancer and much more.

How widespread is this? Consider that approximately 40% of the United States population has fatty liver disease which is driven by insulin resistance—and very few know it.

Quoted in Technology Networks Cancer Research, the lead author states:

“Our study highlights the growing understanding that cancer does not develop in isolation—it is influenced by a person’s overall health, including metabolic conditions like diabetes. This problem is urgent because the epidemic of obesity-driven diabetes is worsening and now affects over 537 million adults worldwide. This finding adds to the idea that treating underlying conditions, not just cancer itself, could improve patient outcomes,” said Denis, who also is co-director of the BU-BMC Cancer Center.”

*Exosome science is already used in the ExoDx Prostate Test, a urine test for more accurate risk assessment of prostate cancer when PSA is elevated.