The tremendous clinical potential of the microbiota in the treatment of breast cancer: the next frontier

Abstract

Although significant advances have been made in the diagnosis and treatment of breast cancer (BC) in recent years, BC remains the most common cancer in women and one of the main causes of death among women worldwide. Currently, more than half of BC patients have no known risk factors, emphasizing the significance of identifying more tumor-related factors. Therefore, we urgently need to find new therapeutic strategies to improve prognosis. Increasing evidence demonstrates that the microbiota is present in a wider range of cancers beyond colorectal cancer. BC and breast tissues also have different types of microbiotas that play a key role in carcinogenesis and in modulating the efficacy of anticancer treatment, for instance, chemotherapy, radiotherapy, and immunotherapy. In recent years, studies have confirmed that the microbiota can be an important factor directly and/or indirectly affecting the occurrence, metastasis and treatment of BC by regulating different biological processes, such as estrogen metabolism, DNA damage, and bacterial metabolite production. Here, we review the different microbiota-focused studies associated with BC and explore the mechanisms of action of the microbiota in BC initiation and metastasis and its application in various therapeutic strategies. We found that the microbiota has vital clinical value in the diagnosis and treatment of BC and could be used as a biomarker for prognosis prediction. Therefore, modulation of the gut microbiota and its metabolites might be a potential target for prevention or therapy in BC.

Keywords: Breast cancer; Mechanisms; Microbiota; Therapy.

Fig. 1

A multitude of factors affect the human gut microbiota and the association between gut microbiota and the onset of BC

Fig. 2

The microbiota affects BC tumorigenesis and metastasis by regulating estrogen metabolism. Estrogen is metabolized to glucuronic acid by glucuronidation and sulfonation, excreted into the gut by bile, and excreted in urine or feces. A small fraction of conjugated estrogens is uncoupled and absorbed through the mucosa into the circulation as free estrogens, resulting in estrogen exposure and thus an increased risk of BC

Fig. 3

The microbiota affects BC tumorigenesis and metastasis by causing DNA damage. The mechanism of DNA double-strand breaks (DSBs) repair involves non-homologous end joining. The accumulation of mismatch repairs in cells over time can result in chromosomal instability and an increased risk of eventual tumor development

Fig. 4

The microbiota affects BC tumorigenesis and metastasis by bacterial metabolites, including the release of its own metabolites [e.g., short-chain fatty acids (SCFAs), cadaverine], host metabolite modifications (e.g., secondary bile acids), or inosine synthesis, inducing changes in gene expression or regulating host signaling