An unhealthy gut triggers changes in normal breast tissue that may help breast cancer metastasize, according to new, early research from the University of Virginia (UVA) Cancer Center published by Feng et al in Cancer Immunology Research. The researchers found that when the gut microbiome is disrupted by poor diet, long-term antibiotic use, obesity, or other factors, it reprograms mast cells in healthy breast tissue to facilitate cancer’s spread.
The findings could help scientists develop ways to keep breast cancer from metastasizing. When it does, it is often deadly: only 29% of women with metastatic breast cancer survive 5 years; for men with metastatic breast cancer, that figure is just 22%. The discovery may also assist doctors in predicting which patients are at greatest risk of cancer recurrence after treatment.
“We showed [that] gut commensal dysbiosis, an unhealthy and inflammatory gut microbiome, systemically changes the mammary tissues of mice that do not have cancer. The tissue changes enhance infiltration of mast cells that, in the presence of a tumor, facilitate breast tumor metastasis,” said researcher Melanie R. Rutkowski, PhD, of UVA Cancer Center and Associate Professor of Microbiology, Immunology, and Cancer Biology at the UVA School of Medicine. “Mast cells recruited into the tissue environment during dysbiosis restructure the tissue architecture in such a way that tumor cells metastasize to other organs.”
The Microbiome and Breast Cancer
Dr. Rutkowski has been a pioneer in unveiling the surprising relationship between gut health and breast cancer. Her latest work reveals complex interactions between our gut microbes and mast cells in the breast. The current study suggests that the gut microbiome can systemically influence mast cell behavior and function in the presence of tumors.
Dr. Rutkowski and her team found that an unhealthy microbiome caused mast cells to accumulate in the breast. These changes continued after tumor formation in a mouse model of hormone receptor (HR)-positive breast cancer, making the breast tissue a prime launching ground for the spread of cancer into other parts of the body.
Furthermore, the scientists found that the mast cells increased the amount of collagen in the mice’s breast tissue and spurred earlier cancer spread. Blocking the process that led to mast-cell accumulation prevented both, significantly reducing the spread of tumors to the lungs.
Based on their lab results, the researchers examined tissue samples taken from human patients with HR-positive breast cancer. They found that these patients, like the mice, had an increased number of mast cells and increased deposits of collagen. The number of mast cells correlated with the amount of collagen and, notably, the patients’ risk for a recurrence of breast cancer.
“Mast cells have had a controversial role in breast cancer, with some studies identifying a positive correlation with outcome, while others have identified negative associations,” said Dr. Rutkowski. “Our investigation suggests that to better define the relationship between mast cells and risk for breast tumor metastasis, we should consider the mast cell functional attributes, tissue collagen density, and mast cell location with respect to the tumor.”
Ultimately, she said, doctors may be able to target the gut–mast cell relationship in patients with breast cancer to help prevent the cancer from recurring and spreading. They also may be able to use the discovery to identify patients at risk for disease recurrence, allowing them to tailor the treatment strategy for the prevention of metastatic disease.
“Personalized medicine in oncology is a promising approach to facilitate better outcomes for patients,” said first study author Tzu-Yu Feng, PhD, a research associate at UVA. “Our research on the gut–mast cell axis has identified possible intervention points that could be targeted for a customized approach to therapy. The ultimate goal would be to improve survival for patients diagnosed with breast cancer.”
Disclosure: The work was supported by Susan G. Komen, the National Institutes of Health’s National Cancer Institute (NCI), and the American Cancer Society. Additional support came from the UVA Cancer Center, the Biotechnology and Biological Sciences Research Council Strategic Programme in Gut Microbes and Health, and Cancer Research UK. For full disclosures of the study authors, visit aacrjournals.org.
