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The Microbiome and Breast Cancer

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Breast cancer is a complex and heterogeneous disease that one in eight women will be diagnosed with, and that significantly contributes to overall female cancer mortality rates.[1,2]

The complexity of the disease is associated with both classification and aetiology, with more than 20 recognised histopathological subtypes of breast cancer exhibiting certain molecular, hormonal, genetic and clinical characteristics.[3-5]

Currently, its specific aetiology is unconfirmed but is thought to be associated with a complicated inter-relationship between micro- and macroenvironmental and genetic antecedents.[2,6]

One micro-environment that is a current area of research is the potential role of local and systemic microbiomes in the onset and progression of breast cancer.[7-10] The human microbiome is comprised of bacteria, fungi, protozoa and viruses in the body and distinct microbial genera and diversity patterns have been observed at different body locations.[9,11,12]

Recent studies have observed differences in the local breast microbiome of subjects with malignant breast cancer compared to those with benign tumours or who were disease-free.[2,9]

In this prospective study, Hieken et al investigated the microbiome in human breast tissue and the overlying skin (n = 33), and the differences in the microbiome of malignant versus benign breast tissue (n = 28).

All subjects (age range = 33-84 years) had non-mastectomy breast surgery for malignant (n = 17) or benign (n = 16) disease. Of those with malignancies, all were oestrogen and progesterone positive with 29% also being HER-2neu positive. The majority of the subjects (n = 22) were post-menopausal, with a small number pre-menopausal (n = 9).

There were two main findings from this study. Firstly, breast tissue had its own microbiome that was distinct from the overlying breast skin tissue, surface skin and buccal samples. Alpha- and beta-diversity analyses showed that breast tissue was richer in bacterial species than skin tissue and that the highly significant difference was primarily in the rare lineages (unweighted UniFrac analysis MiRKAT, p = <1e-4, weighted analysis MiRKAT, p = 0.14).

Secondly, the microbiota in breast skin tissue was significantly different in subjects with malignant versus benign disease.

Beta-diversity assessment with unweighted UniFrac analysis observed significant differences (MiRKAT, p = 0.009), but not with weighted UniFrac analysis, suggesting that the main variation also involved less common lineages (Fusobacterium, Atopobium, Hydrogoenlphaga, Gluconacetobacter and Lactobacillus, unadjusted p < 0.05).

A similar finding was noted by Urbaniak et al[2] although the specific bacterial profiles observed differed from that seen by Hieken et al.[9]

Women with malignant (n = 45) or benign (n = 13) tumours versus healthy controls (n = 23) (age range = 19-90 years) were assessed to investigate the potential role of the local microbiome in breast cancer development.

Different microbial profiles were observed in malignant breast tissue compared to the control group, with a higher abundance of Enterobacteriaceae and Staphylococcus taxa in cancer-affected subjects. Also, three E. coli isolates from the Enterobacteriaceae family and one from the Staphylococcus taxa demonstrated in vitro the capacity to cause DNA double-strand breaks, the accumulation of which may lead to cancer.

These studies suggest that in the presence of breast cancer, variations in the local tissue microbiome occurs, however whether this is a consequence of the disease or if it has mechanistic significance for disease onset and progression is yet to be determined.[10]

Potential mechanisms by which the microbiome may be involved in malignant disease onset, progression or inhibition include via the metabolism of hormones including oestrogen, the induction or modulation of inflammation, immunity or genotoxicity and the synthesis of carcinogenic metabolites.[1,2,6,10,13-15]

Further research is required to investigate the role that the microbiota has to play in the aetiology of breast cancer, the significance of specific microbial patterns and how manipulation of local or systemic microbiomes may influence disease onset and progression.

References

  1. Kwa M, Plottel CS, Blaser MJ, et al. The intestinal microbiome and estrogen receptor-positive female breast cancer. J Nat Can Inst 2016 Apr 22;108(8):djw029. [Full text]
     
  2. Urbaniak C, Gloor GB, Brackstone M, et al. The microbiota of breast tissue and its association with breast cancer. Appl Environ Microbiol 2016;82(16):5039-5048. [Full text]
     
  3. Weigelt B, Geyer FC, Reis-Filho JS. Histological types of breast cancer: how special are they? Mol Oncol 2010;4(3):192-208. [Full text]
     
  4. Sinn HP, Kreipe H. A brief overview of the WHO classification of breast tumours, 4th edition, focussing on issues and updates from the 3rd edition. Breast Care 2013;8(2):149-154. [Full text]
     
  5. Briskin C, Hess K, Jeitziner R. Progesterone and overlooked endocrine pathways in breast cancer pathogenesis. Endocrinology 2015;156(20);3422-3450. [Full text]
     
  6. Erdman SE, Poutahidis T. Gut bacteria and cancer. Biochim Biophys Acta 2015;1856(1):86-90. [Full text]
     
  7. Xuan C, Shamonki JM, Chung A, et al. Microbial dysbiosis is associated with human breast cancer. PLoS One 2014;9(1):e83744. [Full text]
     
  8. De Spiegeleer B, Verbeke F, D’Hondt M, et al. The quorum sensing peptides PhrG, CSP and EDF promote angiogenesis and invasion of breast cancer cells in vitro. PLoS One 2015:10(3):e0119471. [Full text]
     
  9. Hieken TJ, Chen J, Hoskin TL, et al. The microbiome of aseptically collected human breast tissue in benign and malignant disease. Sci Rep 2016;6:30751. [Full text]
     
  10.  Reid G. Can breast microbiota provide protective effects against cancer? Future Microbiol 2016;11(8):987-989. [Full text]
     
  11. Plottel CS, Blaser MJ. Microbiome and malignancy. Cell Host Microbe 2011;10(4):324-335. [Full text]
     
  12. The Human Microbiome Project Consortium. Structure, function and diversity of the healthy human microbiome. Nature 2012;486(7402):207-214. [Full text]
     
  13.  Sheflin AM, Whitney AK, Weir TL. Cancer-promoting effects of microbial dysbiosis. Curr Oncol Rep 2014;16(10):406. [Full text]
     
  14. Braundmeier AG, Lenz KM, Inman KS, et al. Individualized medicine and the microbiome in reproductive tract. Front Physiol 2015;6:97. [Full text]
     
  15. Rutkowski MR, Conejo-Garcia JR. Size does not matter: commensal microorganisms forge tumour-promoting inflammation and anti-tumour immunity. Oncoscience 2015;2(3):239-246. [Full text]

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georgia.marrion's picture
Georgia Marrion
Georgia is a naturopath and nutritionist of more than 12 years in the complementary medicine industry, with experience in areas including clinical practice, practitioner consultant, writing, lecturing, product development and regulatory affairs. With a Masters in Human Nutrition, her main interest areas are gastrointestinal and women's health, and she is passionate about providing information to people to help them optimise their overall health.