Microbiome and breast cancer: A systematic review and meta-analysis.

Background: Dysbiosis characterizes breast cancer (BC) through direct or indirect interference in a variety of biological pathways, therefore specific microbial patterns and diversity may be a biomarker for BC diagnosis and prognosis. However, there is still much to determine on the complex interplay of gut microbiome and BC. Objective: To evaluate the microbial alteration in BC patients as compared with control subjects, to explore the gut microbial modification from a range of different BC treatments, and to identify the impact of microbiome patterns on the same treatment-receiving BC patients. Methods: A literature search was conducted using electronic databases such as PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library to April 2021. The search was limited to adult BC women and the English language. A prespecified subgroup analysis in BC patients was performed. The results were synthesized quantitatively and qualitatively using random-effects meta-analysis. Results: A total of 33 studies were included in the review, accounting for 20 case-control, 8 cohort, and 5 non-randomized intervention studies. In the meta-analysis, the bacterial DNA load is reduced in the tumor compared with paired normal breast and healthy breast tissue, and interestingly, there is an inverse correlation of the bacterial load in different breast tumor stages. From the intervention studies, it revealed 41 species related to breast tumors with a predominance of Gemella haemolysans and Streptococcus mitis, and after chemotherapy, the number of species per patient was elevated by a mean of 2.6 (SD = 4.7, p = 0.052). Also, the tumor tissue showed a significant reduction of transcripts of microbial sensors such as TLR2, TLR5, and TLR9, cytoplasmic microbial sensors like NOD1 and NOD2, and the levels of BPI, MPO, and PRTN3. It found that the post-menopausal group has higher leucine- and valine-arylamidase, {beta}-glucuronidase, and esterase-lipase activities in contrast to pre-menopausal and healthy groups. Conclusions: This systematic review elucidates the complex network of the microbiome, BC, and the therapeutic options, expecting to provide a link for stronger research studies and toward personalized medicine to improve their quality of life.