Intestinal microbiota influences clinical outcome and side effects of early breast cancer treatment

Abstract

The prognosis of early breast cancer (BC) relies on cell autonomous and immune parameters. The impact of the intestinal microbiome on clinical outcome has not yet been evaluated. Shotgun metagenomics was used to determine the composition of the fecal microbiota in 121 specimens from 76 early BC patients, 45 of whom were paired before and after chemotherapy. These patients were enrolled in the CANTO prospective study designed to record the side effects associated with the clinical management of BC. We analyzed associations between baseline or post-chemotherapy fecal microbiota and plasma metabolomics with BC prognosis, as well as with therapy-induced side effects. We examined the clinical relevance of these findings in immunocompetent mice colonized with BC patient microbiota that were subsequently challenged with histo-compatible mouse BC and chemotherapy. We conclude that specific gut commensals that are overabundant in BC patients compared with healthy individuals negatively impact BC prognosis, are modulated by chemotherapy, and may influence weight gain and neurological side effects of BC therapies. These findings obtained in adjuvant and neoadjuvant settings warrant prospective validation.

The Microbiome as a Potential Target for Therapeutic Manipulation in Pancreatic Cancer

“…The study showed some similar findings of the potential use of the microbiome as a prognostication biomarker, and the potential of altering breast cancer into a tumour-infiltrating lymphocyte (TIL)-enriched tumour microenvironment, thus making it amenable to ICI therapy. This study [167] also elucidated other potential roles of the microbiome that have not been discussed above concerning PDAC. In this study, they have found other predictive biomarker roles of the microbiome, predictive of neurological treatment side effects and the potential to be utilised as a predictive tool of the efficacy of neoadjuvant and adjuvant chemotherapy [167].…”

“…This study [167] also elucidated other potential roles of the microbiome that have not been discussed above concerning PDAC. In this study, they have found other predictive biomarker roles of the microbiome, predictive of neurological treatment side effects and the potential to be utilised as a predictive tool of the efficacy of neoadjuvant and adjuvant chemotherapy [167].…”

“…A very recent paper by Terrisse et al investigated the influence of the microbiome on the clinical outcome and side effects of early breast cancer treatment [167]. The study showed some similar findings of the potential use of the microbiome as a prognostication biomarker, and the potential of altering breast cancer into a tumour-infiltrating lymphocyte (TIL)-enriched tumour microenvironment, thus making it amenable to ICI therapy.…”

Cetuximab-Modified Human Serum Albumin Nanoparticles Co-Loaded with Doxorubicin and MDR1 siRNA for the Treatment of Drug-Resistant Breast Tumors

“…All mice were housed in sawdust-lined cages with constant temperatures (22–25°C) and suitable humidity (50 ± 2.0%). When the tumor (volume (mm 3 ) = length * width 2 /2) grew to approximately 600 mm 3 , the tumor-bearing mice were randomly divided into 5 groups (n =8): normal saline (NS), DOX (1.2 mg/kg), DOX+siMDR1 (contain 1.2 mg/kg DOX and 0.8 μg/kg siRNA), H/D (contain 1.2 mg/kg DOX), H/D/M (contain 1.2 mg/kg DOX) and C-H/D/M (contain 1.2 mg/kg DOX). Then once every other day via intravenous injection the mice were treated with their corresponding therapeutic regimen or NS.…”

“…Breast cancer is the most common cause of death and one of the most prevalent cancers among women worldwide. 1 , 2 As people pay more and more attention to cancer, the treatment strategies for tumors are gradually increasing, including surgery, chemotherapy, immunotherapy, and other methods. Studies have shown that phototherapeutic or chemotherapeutic nano-delivery systems can reduce metastasis through enhanced tumor-killing efficiency.…”