Breast tissue, oral and urinary microbiomes in breast cancer

Abstract

It has long been proposed that the gut microbiome contributes to breast carcinogenesis by modifying systemic estrogen levels. This is often cited as a possible mechanism linking breast cancer and high-fat, low-fiber diets as well as antibiotic exposure, associations previously identified in population-based studies. More recently, a distinct microbiome has been identified within breast milk and tissue, but few studies have characterized differences in the breast tissue microbiota of patients with and without cancer, and none have investigated distant body-site microbiomes outside of the gut. We hypothesize that cancerous breast tissue is associated with a microbiomic profile distinct from that of benign breast tissue, and that microbiomes of more distant sites, the oral cavity and urinary tract, will reflect dysbiosis as well. Fifty-seven women with invasive breast cancer undergoing mastectomy and 21 healthy women undergoing cosmetic breast surgery were enrolled. The bacterial 16S rRNA gene was amplified from urine, oral rinse and surgically collected breast tissue, sequenced, and processed through a QIIME-based bioinformatics pipeline. Cancer patient breast tissue microbiomes clustered significantly differently from non-cancer patients (p=0.03), largely driven by decreased relative abundance of Methylobacterium in cancer patients (median 0.10 vs. 0.24, p=0.03). There were no significant differences in oral rinse samples. Differences in urinary microbiomes were largely explained by menopausal status, with peri/postmenopausal women showing decreased levels of Lactobacillus. Independent of menopausal status, however, cancer patients had increased levels of gram-positive organisms including Corynebacterium (p<0.01), Staphylococcus (p=0.02), Actinomyces (p<0.01), and Propionibacteriaceae (p<0.01). Our observations suggest that the local breast microbiota differ in patients with and without breast cancer. Cancer patient urinary microbiomes were characterized by increased levels of gram-positive organisms in this study, but need to be further studied in larger cohorts.

Microbiome, bile acids, and obesity: How microbially modified metabolites shape anti‐tumor immunity

“…1 The largest study to examine microbes and BC was from The Cancer Genome Atlas (TCGA) wherein Proteobacteria, Actinobacteria, and Firmicutes were shown as the most abundant phyla in breast tumors, which is consistent with our work and others, and reminiscent of the gut. 1,11,14,18,21,168,[172][173][174][175][176]180,181 We detected dysbiosis in breast tumors and tumor-adjacent breast tissue compared to normal tissue from healthy subjects. Recall that Ruminococcus is high in the gut of BC patients 11 and reduced by Mediterranean diet in the mammary glands of monkeys.…”

“…167 Examination of the local microbiome in BC compared to normal tumor-adjacent or normal mammary gland has revealed interesting alterations. 11,14,168,[172][173][174][175][176] The Western diet is associated with obesity and poor tumor outcomes. 177 Cook et al showed for the first time that Mediterranean vs Western diet could alter mammary gland microbes, specifically increasing Lactobacillus by 10-fold and reducing Ruminococcus in the mammary gland of non-human primates.…”

Breast Cancer and Its Relationship with the Microbiota

“…In this regard, it has been proposed that certain gut microbes may play a role in breast carcinogenesis by promoting antitumor immunity and immune surveillance, and/or by modulating systemic estrogen levels [44,45]. BC associations with estrogen levels could reflect differences among individuals in their intestinal microbial communities [46], as shown 50 years ago by Adlercreutz and collaborators, who demonstrated one of the fundamental roles of the gut microbiota [47].…”

Gut microbiota diversity is associated with cardiorespiratory fitness in post‐primary treatment breast cancer survivors

“…Although habitual physical activity is thought to modulate this relationship (McTiernan et al., ), it is unclear whether the benefits of physical activity are driven by changes in adiposity or gut microbiota, because both are associated with systemic oestrogens. Recent comparative analyses of microbiota from urine and local breast tissue (Wang et al., ), in addition to gut microbes (Goedert et al., ), have revealed compositionally distinct microbiomic profiles between women with and without breast cancer. Thus, a complex interaction exists between gut microbiota diversity, adiposity, menopausal status and free‐living physical activity.…”