By Dr. Ananya Mandal, MD

A new study from the researchers at the University of Virginia Cancer Center connects an unhealthy gut microbiome with breast cancer that can become invasive and spread to other organs faster. The results of the study were published in the latest issue of the journal Cancer Research. The study titled, “Pre-existing commensal dysbiosis is a host-intrinsic regulator of tissue inflammation and tumor cell dissemination in hormone receptor-positive breast cancer,” was supported by a Susan G. Komen grant.

Lead researcher, Melanie Rutkowski, from the Department of Microbiology, Immunology and Cancer Biology, in her study found that if the gut microbiome or the microbial contents of the gut of the lab mice are altered, their hormone-receptor-positive breast cancer turned more aggressive. This change in the normal health flora of bacteria within the gut of the mice altered the nature of the cancer and primed it to spread to other organs, write researchers.

The team writes that until now it has been unknown why some of the hormone-receptor positive cancers are more aggressive and invasive compared to others. They looked at intrinsic host factors such as altered gut microbiome called “commensal dysbiosis” and is association with aggressive nature of the cancer.

Rutkowski explained, “When we disrupted the microbiome’s equilibrium in mice by chronically treating them antibiotics, it resulted in inflammation systemically and within the mammary tissue. 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.” She said that in the next part of their study they transplanted the unhealthy microbiome from their test mice to other mice with HR positivie breast cancer using fecal transplant. The results were similar among the recipient mice, she explained. This proved the direct effect of the microbiome on the aggressiveness conversion of the breast cancer.

Experts say that hormone receptor positive cancers or breast cancers that grow under the influence of female hormones estrogen and progesterone form around 65 percent of all breast cancers. These cancers are more responsive to hormone therapy and often show a good outcome. Rutkowski explained that how these cancers will spread and grow is dependent of several factors seen at the time of diagnosis. She said, “One of them is having a high level of [immune] cells called macrophages present within the tissue.” She added, “There have also been studies that have demonstrated that increased amounts of the structural protein collagen in the tissue and tumor also lead to increased breast cancer metastasis.”

She went on to explain that people with an unhealthy gut microbiome have an increased inflammation of the gut. This effect is often sustained and powerful she said. She added, “Disrupting the microbiome resulted in long-term inflammation within the tissue and the tumor environment. 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. Ultimately, based upon these findings, we would speculate that an unhealthy microbiome contributes to increased invasion and a higher incidence of metastatic disease.”

Experts warn that this is an animal study and may not be extrapolated in humans. Rutkowski warns that the team used antibiotics to kill the healthy gut microbes but all antibiotics are not bad and when necessary they must be taken by women who have breast cancer. This study should not prompt women with breast cancer to shun all antibiotics, warn experts. The team adds that more research is necessary to prove the connection between continued antibiotic usage and breast cancer spread. This study was conducted in genetically modified lab mice with the HR positive breast cancer. The actual picture among humans may be different, explains the team.

Doctors and the team of researchers add that this study shows that if the gut microbiome could be maintained then there may be a positive outcome in women with breast cancers. Rutkowski said that this study highlights the importance of having a healthy gut microbiome. She added that many aspects of good health are associated with a healthy gut. This study reveals another reason for maintaining a healthy microbiome.

Rutkowski concluded, “A healthy diet, high in fiber, along with exercise, sleep – all of those things that contribute to positive overall health. If you do all of those things, in theory, you should have a healthy microbiome. And that, we think, is very much associated with a favorable outcome in the long term for breast cancer.”

Source: Pre-existing commensal dysbiosis is a host-intrinsic regulator of tissue inflammation and tumor cell dissemination in hormone receptor-positive breast cancer, Claire Buchta Rosean, Raegan R Bostic, Joshua C. M. Ferey, Tzu-Yu Feng, Francesca N Azar, Kenneth S Tung, Mikhail G Dozmorov, Ekaterina Smirnova, Paula D. Bos and Melanie R Rutkowski, DOI: 10.1158/0008-5472.CAN-18-3464, http://cancerres.aacrjournals.org/content/early/2019/05/07/0008-5472.CAN-18-3464