New research from the University of Virginia suggests an unhealthy gut microbiome can actively promote the spread of breast cancer. Through a series of animal experiments the new study demonstrated how disruptions to gut bacterial populations can drive metastatic spread of tumor cells.
Hormone receptor-positive breast cancer, accounting for around 65 percent of all breast cancers, is known to rapidly spread to lymph nodes and lungs. This metastatic progression is one of the biggest challenges in effectively treating the disease. While the cancer does respond effectively to hormone therapy, it is challenging for clinicians to predict what factors promote early metastatic spread.
This new research set out to investigate the connection between an impaired gut microbiome, known as dysbiosis, and the metastatic spread of breast cancer. Using a mouse model of hormone receptor-positive breast cancer the study discovered that disrupting the animals' microbiome through strong antibiotics resulted in enhanced circulation of tumor cells, particularly to lymph nodes and the lungs.
"When we disrupted the microbiome's equilibrium in mice by chronically treating them antibiotics, it resulted in inflammation systemically and within the mammary tissue," explains Melanie Rutkowski, corresponding author on the new study. "In this inflamed environment, tumor cells were much more able to disseminate from the tissue into the blood and to the lungs, which is a major site for hormone receptor-positive breast cancer to metastasize."
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The study verified the causal relationship between the microbiome dysbiosis and metastatic cancer spread by replicating the experiment using fecal microbiota transplantation to disrupt the animals' microbiome. The results were similar, suggesting the gut microbiome plays a role in regulating tissue inflammation and metastatic cancer spread.
The researchers are careful to note that the volume of antibiotics used in the animal studies were significantly higher than what a human would take in regular clinical scenarios. So this research does not at all imply women with breast cancer should avoid taking courses of antibiotics to treat infections.
Instead, this study points to the potential of using the health of a person's microbiome as a way to evaluate whether they could be at a higher risk of metastatic disease. Having this information at the time of initial diagnosis could help clinicians better calibrate treatments to improve long-term outcomes.
"These findings suggest that having an unhealthy microbiome, and the changes that occur within the tissue that are related to an unhealthy microbiome, may be early predictors of invasive or metastatic breast cancer," says Rutkowski. "Ultimately, based upon these findings, we would speculate that an unhealthy microbiome contributes to increased invasion and a higher incidence of metastatic disease."
The new study was published in the journal Cancer Research.