The Microbiota of Breast Tissue and Its Association with Breast Cancer

Study information

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study design

case-control

Citation

PMID PubMed identifier for scientific articles.

27342554

DOI Digital object identifier for electronic documents.

10.1128/AEM.01235-16

URI Uniform resource identifier for web resources.

Authors

Urbaniak C, Gloor GB, Brackstone M, Scott L, Tangney M, Reid G

Journal

Applied and environmental microbiology

Year

2016

UNLABELLED: 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.

Experiment 1

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Subjects

Location of subjects

Canada

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 patients

Group 1 name Corresponds to the case (exposed) group for case-control studies

BC patients

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Normal adjacent tissue, collected outside the marginal zone (approximately 5 cm away from the tumor), from patients with breast cancer (BC) undergoing lumpectomies or mastectomies.

Group 0 sample size Number of subjects in the control (unexposed) group

12

Group 1 sample size Number of subjects in the case (exposed) group

20

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)

3 months

Lab analysis

Sequencing type

16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene

V6

Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance

Illumina

Statistical Analysis

Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).

centered log-ratio

Statistical test

Mann-Whitney (Wilcoxon)

Significance threshold p-value or FDR threshold used for differential abundance testing (if any)

0.1

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?

Yes

Signature 1

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Source: Figure 3

Description: Differences in relative abundances of taxa exist between healthy and cancer patients. Significance was based on the Benjamini-Hochberg corrected P value of the Wilcoxon rank test (significance threshold, P < 0.1).

Abundance in Group 1: increased abundance in BC patients

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Bacillus
Staphylococcus
Enterobacteriaceae
Comamonadaceae

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Signature 2

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Source: Figure 3

Description: Differences in relative abundances of taxa exist between healthy and cancer patients. Significance was based on the Benjamini-Hochberg corrected P value of the Wilcoxon rank test (significance threshold, P < 0.1).

Abundance in Group 1: decreased abundance in BC patients

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Prevotella
Lactococcus
Corynebacterium
Streptococcus
Micrococcus

Revision editor(s): Ecsharp

Experiment 2

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Differences from previous experiment shown

Subjects

Group 1 name Corresponds to the case (exposed) group for case-control studies

patients with benign tumors

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group

Normal adjacent tissue, collected outside the marginal zone (approximately 5 cm away from the tumor), from patients with benign tumors.

Group 1 sample size Number of subjects in the case (exposed) group

11

Lab analysis

Statistical Analysis

Signature 1

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Source: Supplementary Table S4

Description: ALDEx2 summary comparing relative abundances in breast tissue from healthy women, those with benign tumours and those with cancerous tumours. Bacterial profiles in normal adjacent breast tissue from women with benign tumours are more similar to normal adjacent tissue from women with cancerous tumours rather than healthy controls.

Abundance in Group 1: increased abundance in patients with benign tumors

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Bacillus
Staphylococcus

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Source: Supplementary Table S4

Description: ALDEx2 summary comparing relative abundances in breast tissue from healthy women, those with benign tumours and those with cancerous tumours. Bacterial profiles in normal adjacent breast tissue from women with benign tumours are more similar to normal adjacent tissue from women with cancerous tumours rather than healthy controls.

Abundance in Group 1: decreased abundance in patients with benign tumors

NCBI	Quality Control	Links
Prevotella
Lactococcus

Revision editor(s): Ecsharp