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Breast Microbiome-Immune Interactions May Influence Breast Cancer

Dr. Eng and colleagues found that the breast microbiome may modulate local immune responses that lead to breast cancer.

05/18/2021



A recent study by Cleveland Clinic researchers suggests that interactions between the breast microbiome and local immune responses may influence breast cancer development and progression. Published in Genome Medicine, the findings lay the foundation for future investigation into the factors associated with breast cancer initiation, which will help facilitate the development of improved detection and prevention strategies.

“Although several groups, including ours, have demonstrated that the community of microbes found in breast tissue differs significantly between individuals with and without breast cancer, little is known about the breast microbiome’s role in breast cancer,” said Charis Eng, MD, PhD, chair of the Genomic Medicine Institute and the study’s corresponding author. “Since interactions between the immune system and microbes in the gut are known to contribute to disease, we suspect that a similar interplay could occur in the breast.”

To uncover potential connections between the breast microbiome and breast cancer-related immune responses, the researchers compared the breast microbiota and immune profiles of 221 patients with breast cancer to those of 87 healthy controls (of which 18 were categorized as at high-risk for developing breast cancer).

Breast microbiome correlates with immune features

They found that the breast microbiome composition varied based on tissue type and predictive breast tumor features, including cancer stage, grade, histologic subtype and more. In addition, certain bacteria types were significantly associated with immune features that either promote or protect against breast cancer.

For example, Propionibacterium and Staphylococcus were prominent in healthy, high-risk and tumor-adjacent normal tissues but scarce in tumor tissue. Higher levels of the two bacteria were associated with several genes related to the activation of cancer-fighting T-cells, while lower levels were associated with cancer-promoting immune responses.

“Our study provides evidence that the breast microbiome may modulate immune function to lead to breast cancer,” said Dr. Eng. “Decreased microbial diversity or loss of certain bacteria in breast tumors could disrupt microbiome–immune interactions, resulting in immune dysregulation and tumor formation.”

While further studies are necessary to fully delineate the connection between the breast microbiome and breast cancer, the findings are an important step towards improved breast cancer prevention and treatment strategies. “Ultimately, it may become possible to use diet, probiotics, selective antibiotics or fecal microbiota transplant as well as topical, injected or surgically-applied agents to establish a more anti-tumorigenic breast microbiome that can treat or, better yet, prevent breast cancer,” said Dr. Eng.

Alice Tzeng, MD, PhD, a former medical student who trained in Dr. Eng’s lab, is first author on the study, which was supported in part by the Gray Foundation; Cleveland Clinic VeloSano; and the James and Ruth Levitan Cancer Research Award.

 




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