Breast tissue, oral and urinary microbiomes in breast cancer

From BugSigDB
Needs review
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI Uniform resource identifier for web resources.
Authors
Wang H, Altemus J, Niazi F, Green H, Calhoun BC, Sturgis C, Grobmyer SR, Eng C
Journal
Oncotarget
Year
2017
Keywords:
breast cancer, metagenomics, microbiome, oral, urine
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.

Experiment 1


Needs review

Curated date: 2025/06/27

Curator: Ecsharp

Revision editor(s): Ecsharp

Subjects

Location of subjects
United States of America
Host species Species from which microbiome was sampled. Contact us to have more species added.
Homo sapiens
Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Breast Mamma,Mammary part of chest,Mammary region,Breast,breast
Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Breast cancer breast cancer,breast tumor,cancer of breast,malignant breast neoplasm,malignant breast tumor,malignant neoplasm of breast,malignant neoplasm of the breast,malignant tumor of breast,malignant tumor of the breast,mammary cancer,mammary neoplasm,mammary tumor,primary breast cancer,Breast cancer
Group 0 name Corresponds to the control (unexposed) group for case-control studies
healthy controls
Group 1 name Corresponds to the case (exposed) group for case-control studies
breast cancer patients
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Breast cancer patients eligible were over 18 years of age, female, had tumors greater than or equal to 2 cm in size, were undergoing mastectomy. Patients receiving neo-adjuvant therapy prior to surgery or with active clinical breast infection were excluded from the study.
Group 0 sample size Number of subjects in the control (unexposed) group
24
Group 1 sample size Number of subjects in the case (exposed) group
39

Lab analysis

Sequencing type
16S
16S variable region One or more hypervariable region(s) of the bacterial 16S gene
V3-V4
Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
Illumina

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
0.05
MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
No

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
unchanged

Signature 1

Needs review

Curated date: 2025/06/27

Curator: Ecsharp

Revision editor(s): Ecsharp

Source: Supplementary Table 4: A) Breast Tissue

Description: Taxa Significantly Different in Cancer vs. Non-Cancer Samples by Wilcoxon Rank Sum

Abundance in Group 1: increased abundance in breast cancer patients

NCBI Quality ControlLinks
Betaproteobacteria
Peptoniphilus
Alcaligenaceae
Enterobacteriaceae
Enterobacterales
Lactobacillus
Lactobacillaceae
Bifidobacteriaceae
Bifidobacteriales
Bifidobacterium
Micrococcaceae
Gammaproteobacteria

Revision editor(s): Ecsharp

Signature 2

Needs review

Curated date: 2025/06/30

Curator: Ecsharp

Revision editor(s): Ecsharp

Source: Supplementary Table 4: A) Breast Tissue

Description: Taxa Significantly Different in Cancer vs. Non-Cancer Samples by Wilcoxon Rank Sum

Abundance in Group 1: decreased abundance in breast cancer patients

NCBI Quality ControlLinks
Corynebacteriaceae
Corynebacterium
Atopobium
Methylobacterium
Methylobacteriaceae
Catonella
Gemellaceae
Order GemellalesOrder Gemellales

Revision editor(s): Ecsharp

Experiment 2


Needs review

Curated date: 2025/06/30

Curator: Ecsharp

Revision editor(s): Ecsharp

Differences from previous experiment shown

Subjects

Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
Urine Urine,urine
Group 0 sample size Number of subjects in the control (unexposed) group
19
Group 1 sample size Number of subjects in the case (exposed) group
46

Lab analysis

Statistical Analysis

Statistical test
LEfSe
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
2
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
menopause

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased

Signature 1

Needs review

Curated date: 2025/06/30

Curator: Ecsharp

Revision editor(s): Ecsharp

Source: Supplementary Table 4: B) Urine

Description: Taxa Significantly Different in Cancer vs. Non-Cancer Samples Independent of Menopausal Status

Abundance in Group 1: increased abundance in breast cancer patients

NCBI Quality ControlLinks
Actinomycetales
Actinomyces
Corynebacteriaceae
Corynebacterium
Caryophanaceae
Propionibacteriaceae
Streptococcaceae
Streptococcus
Bacillales
Alphaproteobacteria
Staphylococcaceae
Staphylococcus

Revision editor(s): Ecsharp

Experiment 3


Needs review

Curated date: 2025/06/30

Curator: Ecsharp

Revision editor(s): Ecsharp

Differences from previous experiment shown

Subjects

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
Menopause Change of Life, Female,Menopause,menopause
Group 0 name Corresponds to the control (unexposed) group for case-control studies
Premenopausal women
Group 1 name Corresponds to the case (exposed) group for case-control studies
Peri/postmenopausal women
Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
Urine samples from patients with peri/postmenopausal menopausal status from the entire cohort, consisting of both cancer and healthy patients.
Group 0 sample size Number of subjects in the control (unexposed) group
32
Group 1 sample size Number of subjects in the case (exposed) group
44

Lab analysis

Statistical Analysis

Statistical test
Mann-Whitney (Wilcoxon)
LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
Not specified
Confounders controlled for Confounding factors that have been accounted for by stratification or model adjustment
Not specified

Alpha Diversity

Shannon Estimator of species richness and species evenness: more weight on species richness
increased

Signature 1

Needs review

Curated date: 2025/06/30

Curator: Ecsharp

Revision editor(s): Ecsharp

Source: Supplementary Table 4: B) Urine

Description: Taxa Significantly Different in Premenopausal vs. Peri/Postmenopausal Patient Samples by Wilcoxon Rank Sum

Abundance in Group 1: increased abundance in Peri/postmenopausal women

NCBI Quality ControlLinks
Facklamia
Oscillospiraceae
Tissierellaceae
Peptoniphilus
Actinomycetaceae
Clostridia
Clostridiales bacterium
Aerococcaceae
Actinomycetales
Coprococcus
Campylobacterales
Campylobacteraceae
Campylobacter
Epsilonproteobacteria
Anaerococcus
Blautia
Propionibacteriaceae
Varibaculum
Dialister
Genus 1-68Genus 1-68
Porphyromonadaceae
Helcococcus
Pseudomonadota
Bacteroidia
Bacteroidales
Bacteroidota
Veillonellaceae
Actinobaculum
Porphyromonas
Bacteroidaceae
Bacteroides
Dorea
Trueperella
bacterium PH2
Corynebacteriaceae
Corynebacterium
Proteus
Ruminococcus
Prevotellaceae
Prevotella
Roseburia
Enterococcaceae
Actinomycetota
Actinomyces
Desulfovibrionales
Desulfovibrionaceae
Deltaproteobacteria
Bilophila
Finegoldia

Revision editor(s): Ecsharp

Signature 2

Needs review

Curated date: 2025/06/30

Curator: Ecsharp

Revision editor(s): Ecsharp

Source: Supplementary Table 4: B) Urine

Description: Taxa Significantly Different in Premenopausal vs. Peri/Postmenopausal Patient Samples by Wilcoxon Rank Sum

Abundance in Group 1: decreased abundance in Peri/postmenopausal women

NCBI Quality ControlLinks
Lactobacillus
Lactobacillaceae
Shuttleworthella
Lactobacillales
Bacilli
Bacillota

Revision editor(s): Ecsharp