Breast cancer is associated with dysbiosis of the microbiome

Breast cancer is the most common type of cancer among women. Some of the known main risk factors are genetic predispositions, being overweight, smoking and the use of hormone replacement therapy. A study published in February 2020 in the journal Frontiers in Oncology put an additional possible risk factor on the map: a microbiome that is out of balance (1). Interestingly, the microbiome findings were not only made in the stool and gut microbiome, that are organs in which the microbiome therein has already been associated with a plethora of diseases. Also, the breast- and milk microbiome were found to be out of balance in the cancer patients. However, the path towards a full understanding of the connection between the breast microbiome and breast cancer has only just begun.

The breast microbiome

The fact that the breast tissue isn’t sterile, but in addition to fat cells and lymph nodes also contains relatively specific microbes, is in scientific terms a relatively recent finding (2). It is very likely that in breast cancer patients specific bacteria that could protect against cancer are present in lower amounts. In any case, measures of bacterial dysbiosis are good markers of the risk of cancer development in breast tissue (2).

Infections as a cause of cancer

Indeed, in light of the above, many studies point to specific infections being a cause of tumor development. About 5-14 percent of all new cancer cases worldwide are estimated to have infections as the primary direct cause. As much as ten pathogens have been shown to have a clear correlation with different cancers. The most common of them are Helicobacter pylori, hepatitis B virus or hepatitis C virus (3). Interestingly, a correlation between Epstein-Barr virus (EBV) as well as herpes virus 4 with mammary gland cancer was found. In a study, 40 percent of all breast cancer cases a diagnosis of infection with the mentioned viruses was made (4). The same type of findings was also made with the human papilloma virus.

Conversely, it makes sense that these insights also could be applied to breast cancer prevention strategies. Trying to keep the breast microbiome balanced, by way of a good lifestyle, including “microbiome-friendly” products, can definitively be an adjunct to cancer prevention.

The milk microbiome

The composition of the milk microbiome is influenced by pregnancy, lifestyle, antibiotics, and nutrition. The bacteria in mother’s milk originate mostly from the gastrointestinal tract and is transferred to the infant through breast feeding. Also in this regard we see that breast feeding is very complex and what valuable contribution the mother can offer in terms of a strong microbiome for the youngest among us. Interestingly, there is a mutual benefit for child and mother, because the infant’s oral microbiome is to some extent transferred to the mother’s skin. 

The composition of the breast- and milk microbiome is almost identical and consists foremost of Proteobacteria, followed by Firmicutes, Actinobacteria and Bacteroidetes (5). Subsequent studies even found that the mother’s milk microbiome differ based on where in the world you live. In total, mother’s milk contains about 360 different species of procaryotes.

There is no doubt that this complex composition is important both for the development of the infant and for the foundation of the health of the breasts of the mother. Analyses of the metagenome on the species level show that healthy women harbor a diverse microbiome, whereas in women with acute mastitis Staphylococcus aureus is dominating, and in women with sub-acute mastitis Staphylococcus epidermis is dominating. Altogether, in women who suffer from mastitis, the bacterial diversity is reduced (6).

The gut microbiome

While the connection between breast cancer and the breast or milk microbiome is clear, it is all the more remarkable that changes in the intestinal microbiome can also promote cancer development in organs distant from the intestine. Microbes in the gut break down otherwise indigestible fiber into short-chain fatty acids, produce amino acids and vitamins, and help absorb minerals. At the same time, they break down toxins and carcinogens. An intact microbiome lays the foundation for an intact immune system and protects against diseases of all kinds.

As far as breast cancer is concerned, other studies indicate that the composition of the gut microbiome is decisive in terms of whether certain metabolic products that can promote or inhibit breast cancer will be produced, for example. One example is cadaverine, a metabolite that is formed from the amino acid lysine when bacterial protein is broken down. In the early stages of breast cancer, cadaverine levels are reduced, which promote cancer cell growth (7).

Regular consumption of lignans, such as those found in sunflower or pumpkin seeds, flaxseed or legumes, has been shown to promote a resilient gut microbiome. It has also been shown that women who consumed more than 30 g of fiber, fruit or seeds daily had a lower risk of breast cancer than a control group. Eating more raw vegetables reduced the risk of breast cancer by as much as 34% (8).

Prevention and treatment

In addition to the tips mentioned for microbiome-friendly nutrition, the authors of a study also ventured into other research approaches. Experiments in mice were able to show that feeding milk fermented with Lactobacillus helveticus R389 slowed tumor growth in estrogen-dependent breast cancer. This is probably also due to the reduction in IL-6, an inflammatory signaling substance in our immune system that plays a major role in estrogen-dependent tumors (9).

On the other hand, there are also promising attempts to inhibit specific bacterial enzymes that slow down the metabolism of cancer drugs such as irinotecan. Strong side effects of certain cytostatics (cancer drugs) can thus be reduced to a large extent (10).

Targeted and scientifically based probiotic treatments could promote the functionality of the microbiome in the future or restore the intestinal microbiome and thus support the body's natural defenses.

As a preventive measure, the authors suggest developing antibacterial agents in such a way that only specific microorganisms and only certain sections of the intestinal tract are affected.

Sources / References:

1. Eslami-S Z, Majidzadeh-A K, et al. Microbiome and Breast Cancer: New Role for an Ancient Population. Front. Oncol. 2020, https://www.frontiersin.org/articles/10.3389/fonc.2020.00120/full

2. O'Connor H, MacSharry J, Bueso YF, Lindsay S, Kavanagh EL, Tangney M, et al. Resident bacteria in breast cancer tissue: pathogenic agents or harmless commensals? Disc Med. 2018, https://www.discoverymedicine.com/Hugh-OConnor/2018/09/resident-bacteria-in-breast-cancer-tissue-pathogenic-agents-or-harmless-commensals/

3. De Martel C, Ferlay J, et al. Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. Lancet Oncol. 2012, https://pubmed.ncbi.nlm.nih.gov/?Db=pubmed&Cmd=ShowDetailView&TermToSearch=22575588

4. Fina F, Romain S, et al. Frequency and genome load of Epstein-Barr virus in 509 breast cancers from different geographical areas. Br J Cancer, 2001, https://pubmed.ncbi.nlm.nih.gov/?Db=pubmed&Cmd=ShowDetailView&TermToSearch=11259092

5. Costantini L, Magno S, et al. Characterization of human breast tissue microbiota from core needle biopsies through the analysis of multi hypervariable 16S-rRNA gene regions. Sci Rep., 2018, https://pubmed.ncbi.nlm.nih.gov/?Db=pubmed&Cmd=ShowDetailView&TermToSearch=30442969

6. Jiménez E, de Andrés J, et al. Metagenomic analysis of milk of healthy and mastitis-suffering women. J Human Lactation, 2015, https://journals.sagepub.com/doi/abs/10.1177/0890334415585078

7. Kovács T, Mikó E, et al. Cadaverine, a metabolite of the microbiome, reduces breast cancer aggressiveness through trace amino acid receptors. Sci Rep., 2019, https://www.nature.com/articles/s41598-018-37664-7

8. Sieri S, Krogh V, Pala V, Muti P, Micheli A, Evangelista A, et al. Dietary patterns and risk of breast cancer in the ORDET cohort. Cancer Epidemiol Prev Biomark., 2004, https://cebp.aacrjournals.org/content/13/4/567.short

9. de Moreno de LeBlanc A, Matar C, Theriault C, Perdigon G. Effects of milk fermented by Lactobacillus helveticus R389 on immune cells associated to mammary glands in normal and a breast cancer model. Immunobiology., 2005, https://www.sciencedirect.com/science/article/abs/pii/S0171298505001014

10. Wallace B, Roberts A, et al. Structure and inhibition of microbiome β-glucuronidases essential to the alleviation of cancer drug toxicity. Chem Biol., 2015, https://www.sciencedirect.com/science/article/pii/S1074552115003257