Modulating Microbiota as a New Strategy for Breast Cancer Prevention and Treatment

Abstract

Breast cancer (BC) is the most common cancer in women in the United States. There has been an increasing incidence and decreasing mortality rate of BC cases over the past several decades. Many risk factors are associated with BC, such as diet, aging, personal and family history, obesity, and some environmental factors. Recent studies have shown that healthy individuals and BC patients have different microbiota composition, indicating that microbiome is a new risk factor for BC. Gut and breast microbiota alterations are associated with BC prognosis. This review will evaluate altered microbiota populations in gut, breast tissue, and milk of BC patients, as well as mechanisms of interactions between microbiota modulation and BC. Probiotics and prebiotics are commercially available dietary supplements to alleviate side-effects of cancer therapies. They also shape the population of human gut microbiome. This review evaluates novel means of modulating microbiota by nutritional treatment with probiotics and prebiotics as emerging and promising strategies for prevention and treatment of BC. The mechanistic role of probiotic and prebiotics partially depend on alterations in estrogen metabolism, systematic immune regulation, and epigenetics regulation.

Keywords: breast cancer; breast microbiota; epigenetics; gut microbiota; prebiotics; probiotics.

Figure 1

The origin and anti-cancer roles of breast microbiota and milk microbiota. NAF, nipple aspirate fluid; HMOs, human milk oligosaccharides; DC, dendritic cell; SCFAs, short-chain fatty acids; LPS, lipopolysaccharides; and EMT, epithelial–mesenchymal transition.

Figure 2

Probiotics and beneficial bacteria with probiotics effects in BC. A higher abundance of ben eficial bacteria was associated with induced protective immune responses and improved conventional immunotherapy treatments. Bacterial metabolite profiles were changed. Anti-cancer mechanistic roles of probiotics were mediated by inhibited tumor cell survival and induced apoptosis.

Figure 3

Prebiotics and dietary supplements having prebiotic effects in BC. Prebiotics consumption increased fiber and bioactive phytochemicals levels in situ and promoted the growth of probiotics. Tumor size, weight, metastasis, and EMT were reduced by protective bacterial metabolites, reduced pro-inflammatory status, up-regulated tumor-suppressor genes, and inhibited tumor cell proliferation.