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Breast Cancer Microbiota Study

Ece Mutlu, MD, Rush University Medical Center, Chicago, IL
Study abstract

We intend to study the role of the gastrointestinal (GI) microbiota in the pathogenesis of breast cancer (BC) in women. Humans are super organisms that represent a fusion of eukaryotic cells of their own, as well as bacteria and archaea that reside in and over the body, primarily in the GI tract. Little is known about the GI microbiota, which represents the most dense and least diverse ecosystem known on earth. It is believed that GI microbiota is passed on from the mother to her infants and remains fairly stable through life. Bacterial cells in the GI tract outnumber human cells in the body by about 10 fold and carry thousands of additional genes which can rapidly evolve under the pressure of changing environmental factors. The GI tract microbiota approximately weighs about 1 kg in a human being and is estimated to have a metabolic activity comparable to the human liver. A recent metagenomic survey of this activity shows that the bacterial genes for xenobiotics (important in carcinogen and hormone metabolism) are enhanced in the human GI tract.

BC incidence is rising and current genetic factors explain only 5% of the cases seen in clinical practice. The most important factor for BC risk is a family history. The GI microbiota may be a familial factor in BC pathogenesis that is passed on from the mother partly explaining the familial clustering not accounted by known genetic factors. The GI microbiota is also affected by and may be responsible for the observed effects of environmental factors on BC, such as diets, phytoestrogens, alcohol, and obesity. It is also well known that GI microbiota can convert estrogens to their active or inactive forms depending on the bacterial groups present, and can affect the enterohepatic circulation of estrogen and carcinogen metabolism. The GI microbiota can also alter signaling pathways involved in BC pathogenesis or metastasis, such as Rho GTPases, Cox-2 and MAPK. Most recently, infection with an enteric organism that alters GI microbiota was shown to cause BC in animal models. Despite all of this evidence pointing toward a role for GI microbiota in BC and the availability of new molecular biology tools which allow for a wide survey of the GI microbiota and alterations in its gene expression, this topic has not been studied.

Study review

The purpose of this study was to learn more about the types of bacteria that are found in the intestines and how these bacteria metabolize estrogen and other female hormones. The researchers compared bacteria from healthy women, women who had been diagnosed with breast cancer within the last 5 years, and women who had not been diagnosed with breast cancer but had a first-degree relative with breast cancer. The researchers wanted to enroll 700 women. The Call to Action for this study was sent to Army of Women (AOW) members on October 9, 2009. The researchers were able to close enrollment on December 1, 2016, after the AOW provided them with 1,359 women who were interested in enrolling in the study.