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Br J Cancer. 2018 Feb 20;118(4):471-479. doi: 10.1038/bjc.2017.435. Epub 2018 Jan 23.

Postmenopausal breast cancer and oestrogen associations with the IgA-coated and IgA-noncoated faecal microbiota.

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Division of Cancer Epidemiology and Genetics, National Cancer Institute, 9609 Medical Center Drive, Room 6E106, MSC 9767, Bethesda, MD 20892, USA.
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 21702, USA.
Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa 252-0374, Japan.
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Department of Clinical Pathology, Japanese Red Cross Medical Center, Shibuya-ku, Tokyo 150-0012, Japan.
Cancer Research Technology Program, Leidos Biomedical Research Inc., Frederick National Laboratory for Cancer Research, Frederick, MD 21702, USA.
University of Maryland Medical School, Baltimore, MD 21201, USA.
Institute for Health Research, Kaiser Permanente Colorado, Denver, CO 80237, USA.



The diversity and composition of the gut microbiota may affect breast cancer risk by modulating systemic levels of oestrogens and inflammation. The current investigation tested this hypothesis in postmenopausal women by identifying breast cancer associations with an inflammation marker, oestrogen levels, and faecal microbes that were or were not coated with mucosal immunoglobulin A (IgA).


In this population-based study, we compared 48 postmenopausal breast cancer cases (75% stage 0-1, 88% oestrogen-receptor positive) to 48 contemporaneous, postmenopausal, normal-mammogram, age-matched controls. Microbiota metrics employed 16S rRNA gene amplicon sequencing from IgA-coated and -noncoated faecal microbes. High-performance liquid chromatography/mass spectrometry (HPLC/MS) and radioimmunoassay were used to quantify urine prostaglandin E metabolite (PGE-M), a possible marker of inflammation; urine oestrogens and oestrogen metabolites were quantified by HPLC/MS-MS.


Women with pre-treatment breast cancer had non-significantly elevated oestrogen levels; controls' (but not cases') oestrogens were directly correlated with their IgA-negative microbiota alpha diversity (P=0.012). Prostaglandin E metabolite levels were not associated with case status, oestrogen levels, or alpha diversity. Adjusted for oestrogens and other variables, cases had significantly reduced alpha diversity and altered composition of both their IgA-positive and IgA-negative faecal microbiota. Cases' faecal microbial IgA-positive imputed Immune System Diseases metabolic pathway genes were increased; also, cases' IgA-positive and IgA-negative imputed Genetic Information Processing pathway genes were decreased (P⩽0.01).


Compared to controls, breast cancer cases had significant oestrogen-independent associations with the IgA-positive and IgA-negative gut microbiota. These suggest that the gut microbiota may influence breast cancer risk by altered metabolism, oestrogen recycling, and immune pressure.

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