The Microbiota of Breast Tissue and Its Association with Breast Cancer

Abstract

In the United States, 1 in 8 women will be diagnosed with breast cancer in her lifetime. Along with genetics, the environment contributes to disease development, but what these exact environmental factors are remains unknown. We have previously shown that breast tissue is not sterile but contains a diverse population of bacteria. We thus believe that the host's local microbiome could be modulating the risk of breast cancer development. Using 16S rRNA amplicon sequencing, we show that bacterial profiles differ between normal adjacent tissue from women with breast cancer and tissue from healthy controls. Women with breast cancer had higher relative abundances of Bacillus, Enterobacteriaceae and Staphylococcus. Escherichia coli (a member of the Enterobacteriaceae family) and Staphylococcus epidermidis, isolated from breast cancer patients, were shown to induce DNA double-stranded breaks in HeLa cells using the histone-2AX (H2AX) phosphorylation (γ-H2AX) assay. We also found that microbial profiles are similar between normal adjacent tissue and tissue sampled directly from the tumor. This study raises important questions as to what role the breast microbiome plays in disease development or progression and how we can manipulate this for possible therapeutics or prevention. IMPORTANCE This study shows that different bacterial profiles in breast tissue exist between healthy women and those with breast cancer. Higher relative abundances of bacteria that had the ability to cause DNA damage in vitro were detected in breast cancer patients, as was a decrease in some lactic acid bacteria, known for their beneficial health effects, including anticarcinogenic properties. This study raises important questions as to the role of the mammary microbiome in modulating the risk of breast cancer development.

Breast Cancer and Its Relationship with the Microbiota

“…In cancer patients, adjacent histologically normal and non-cancer samples showed no significantly differences in Shannon diversity index or number of observed OTUs. These data are consistent with Urbaniak et al’s findings [67] but disagree with those of Xuan et al [44]. Nevertheless, cancer patient breast tissue microbiota clustered significantly differently from non-cancer patients ( p = 0.03), mainly due to the fact that breast tissue in cancer patients exhibited a significantly decreased relative abundance of Methylobacterium (while this was increased at the site of the tumor in the study of Xuan et al [44]; median 0.10 vs. 0.24, p = 0.03).…”

The development of probiotics for women’s health

“…Hypothesizing that species more accustomed to causing disease and carcinogenic reactions might be present and associated with breast cancer, we conducted 2 studies. We were the first to describe a breast microbiome and demonstrate the differences in the breast microbiome between women with cancer and those who are healthy, suggesting a breast microbiome may indeed have some protective properties (Urbaniak et al 2014(Urbaniak et al , 2016b. While not proving cause and effect, the discoveries could open a new line of investigation into "environmental" factors inducing cancer, and a new method to modify this microbiome to one associated with health.…”

“…In hospital settings, recognition of the value of beneficial microbes is happening, with use of probiotics to reduce mortality and morbidity of low-birth-weight premature babies (Sawh et al 2016) (including in London, Ontario, after 10 years of advocating) and to prevent antibiotic-associated diarrhea including Clostridium difficile infections (Hickson et al 2007;Maziade et al 2015), albeit not all studies have shown efficacy (Allen et al 2013). The success of fecal microbiota transplant in curing C. difficile infections further emphasizes the impact of beneficial microbes (van Nood et al 2013). However, this use is far from universal, in part because some clinicians are not convinced, products may not be available, or administrators are concerned with law suits.…”

Dynamic relationships among tumor, immune response, and microbiota

“…Although results of their analysis were different from ours, some interesting studies may offer support for certain envi ronmental factors being associated with an increased incidence of breast cancer [36,37] . Urbaniak et al demonstrated that breast tissue contains a diverse population of bacteria [38,39] . Using the analysis of 16S rRNA, they showed that the pattern of microbiome is completely different between the adjacent normal breast tissue from women with breast cancer and breast tissue from healthy controls.…”