Saturday, 08 July 2017 13:53

The Breast Microbiome: A Role for Probiotics in Breast Cancer Prevention

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Published in Microbial Sciences

The Role of Bacteria in Breast Cancer

Breast cancer is the leading cause of death among women globally. In the United States, 1 in 8 women will be diagnosed with breast cancer. Modern therapeutic approaches include chemotherapy, radiation therapy, and/or surgery, and we are learning that the breast microbiome may play a major role in the effectiveness of such therapies. For example, antibiotics can impact the effectiveness of chemotherapy, and some cancer drugs, such as cyclophosphamide, may depend on health gut flora. As bariatric surgery has been shown to affect the intestinal microbiome, the effects of breast surgery on the breast microbiome are of great interest—especially as more high-risk women choose to undergo prophylactic mastectomy.

 

Microbes can have a systemic impact, in that they influence the induction, training and function of the immune response and can cause postsurgical infections. Bacterial dysbiosis may also be linked to breast cancer recurrence, particularly for women undergoing breast reconstruction or those who develop post-surgery infections. Some endotoxins, such as TNF, have also been linked to metastatic spread. The breast microbiome may therefore influence cancer susceptibility and recurrence, and commensal bacteria may influence response to therapy by modulating the tumor microenvironment.

 

Characterizing the Breast Microbiome

A diverse population of bacteria can be found within breast tissue, and this diversity is present irrespective of a history of lactation. In a study of 81 women in Canada and Ireland, the most abundant phylum in the healthy breast microbiome was Proteobacteria. The most abundant taxa in the Canadian samples were Bacillus (11.4%), Acinetobacter (10.0%), Enterobacteriaceae (8.3%), Pseudomonas (6.5%), Staphylococcus (6.5%), Propionibacterium (5.8%), Comamonadaceae (5.7%), Gammaproteobacteria (5.0%), and Prevotella (5.0%). In the Irish samples the most abundant taxa were Enterobacteriaceae (30.8%), Staphylococcus (12.7%), Listeria welshimeri (12.1%), Propionibacterium (10.1%), and Pseudomonas (5.3%). In Figure 1, regions of breast tissue sampling are depicted.

 

media 20170708Figure 1. Locations within the breast of tissue samples collected for bacterial analysis. Tissue samples were collected from 43 women from London, Canada, and 38 women from Cork, Ireland, undergoing different breast surgeries. Source

Women with breast cancer have a higher abundance of Enterobacteriaceae, Staphylococcus, and Bacillus when compared to women without breast cancer. Studies that compare microbial profiles in healthy women and those with breast cancer may strengthen our understanding of breast cancer development and assist in the development of therapeutics. E. coli, a member of the Enterobacteriaceae family, is common hospital-borne infectious agent that may have multiple links to breast cancer. Historically, we have seen the association of bacterial species with other human cancers. For example, gastric cancer was linked to Helicobacter pylori infections in the 1990s, and we now also know that Salmonella typhi is linked to some forms of gallbladder cancer. Of note, S. typhi is also a promising carrier of therapeutic agents for melanoma, colon, and bladder cancers.

 

Urbaniak et al. observed that E. coli and S. epidermidis isolated from breast cancer patients induced DNA double-stranded breaks in HeLa cells. They authors state that higher abundances of bacteria that can cause DNA damage in vitro were detected in breast cancer patients. Metabolites of certain bacteria may also be capable of damaging DNA and leading to cancer, but this has not yet been shown in breast cancer.

 

Probiotics: Prevention, Therapy, and Health

Researchers at the University of California San Francisco discussed the human microbiome and breast cancer in a 2017 podcast. Lactobacillus acidophilus, a familiar probiotic found in yogurt and kimchi, can reach the mammary gland and has a number of anti-cancer effects. Women who ingest fermented milk products may experience protective antioxidant effects. Lactobacillus and Lactococcus spp. are more common in healthy breast tissues than in cancerous tissues, and may have a role in breast cancer prevention. For example, Lactobacillus helps to upregulate the immune system and decreases the abundance of C-reactive protein and IL-6, which are pro-inflammatory factors.

 

Harnessing the microbiome for breast cancer therapy is an exciting field of research. According to the UCSF researchers, breastfeeding women who develop lactation mastitis from Staphylococcus may also benefit from Lactobacillus supplements, but studies are pending. For women undergoing mastectomy or breast-conserving surgery, there may also be a role for probiotics in the therapy of postsurgical infections. “Since medical interventions and surgical manipulation of the host are part of everyday practice,” write the authors of a 2017 article on the microbiome and probiotics, “it would be of great interest and importance to examine the precise mechanisms and correlate the reported alterations of the microbiome with the infectious complications in the surgical and/or critically ill patient.” Whether supplementation with Lactobacillus directly prevents breast cancer has yet to be studied.

 

Probiotic treatment is correlated with a significant decrease in the abundance of Escherichia coli and a significant increase in Bifidobacterium, a beneficial gut bacterium. The interplay between gut microbiomes and breast microbiomes have important consequences for breastfeeding—studies suggest that a breastfeeding mother’s gut microbiome has an important role in immune education in her infant. While much is known about breast milk microbiomes, separate sites within the breast (including breast skin tissue, breast skin swabs, and cheek swabs) have unique microbiome signatures. As stated previously, these microbes reside within breast tissue regardless of a history of infection or lactation.

 

Microbes as Diagnostic Markers

RNA extracted from patient saliva samples can provide medically relevant information about the oral microbiome, oral carcinoma, breast cancer, and pancreatic cancer, and salivary RNA assays are therefore a promising tool for medical diagnosis. For oral cancer, the presence of specific salivary microbes (such as Capnocytophaga gingivalis, Prevotella melaninogenica and Streptococcus mitis) can be diagnostic markers. Whether or not certain microbes are coincidental or diagnostic for breast cancer is currently unknown.

 

Considering the Whole Person

The American Association for Cancer Research compared the oral and gut microbiomes in a correlative study of patients with and without breast cancer, and concluded that patients with periodontal disease were at an increased risk of postmenopausal breast cancer. As we continue to learn more about the breast microbiome, it’s important to consider the interactions between various organs and microenvironments within the human body. Characterizing the human microbiome throughout the body may play an important role in calculating cancer risk, diagnosis, and prognosis.

Further Reading

UCSF Podcast on The Human Microbiome and Breast Cancer

Chemotherapy, immunity and microbiota—a new triumvirate?

 

Thumbnail image on the front page: histologic slide of breast cancer cells that have grown out the ducts and into the surrounding tissue displacing normal cells. Stained with H&E and magnified to 200x. By: Dr. Cecil Fox. NIH

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Last modified on Saturday, 08 July 2017 15:01
Jennifer Brubaker

Jennifer Brubaker is a medical student at Ohio University Heritage College of Osteopathic Medicine. She received her graduate degree from Johns Hopkins University in Biotechnology, where she studied Human Molecular Genetics and Emerging Infectious Diseases. She graduated from Boston College with a degree in Biology in 2012.

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