| dc.description.abstract | Chemotherapy can lead to various acute side effects and long-term toxicities, affecting treatment compliance, efficacy, and long-term outcomes. Growing evidence suggests that gastrointestinal (GI) microbiota may influence the efficacy of chemotherapy. However, research on the relationship between the GI microbiome and chemotherapy-induced toxicity is in its infancy, particularly for breast cancer patients. We conducted a case-cohort analysis based on data collected in a prospective follow-up of 396 newly diagnosed and chemotherapy-treated breast cancer patients recruited into the Vietnamese Breast Cancer Study to mainly investigate the influence of the pre-chemotherapy GI microbiota on chemotherapy-induced toxicity. Chemotherapy-induced toxicities were captured through medical chart reviews and patient self-reports and then graded according to the National Cancer Institute Common Toxicity Criteria of Adverse Events classification. Shotgun metagenomic sequencing was employed to characterize the pre-chemotherapy GI microbiome in fecal samples. Associations of overall GI microbial richness, abundance of taxa and microbial metabolic pathways with chemotherapy-induced toxicities were evaluated via multivariable logistic regression. We found a substantial proportion of patients experienced severe (i.e., grade ≥ 3) hematological (38.6%) and GI (12.9%) toxicities during the first-line chemotherapy. Breast cancer surgery, which is always followed by a prophylaxis antibiotics treatment in Vietnam, was associated with significant changes in the GI microbiome profile. Age, income, geographic residence, and delay in diagnosis were also associated with the GI microbiome. Our study found that overall GI microbial richness and multiple microbes were significantly associated with the development of hematological and GI toxicities, although the microbial associations for these two system toxicities differed. Metabolic pathway analyses revealed some novel information on the possible biological mechanisms underlying the interactions between the GI microbiome and chemotherapeutic agents in developing chemotherapy-induced toxicity. In conclusion, severe chemotherapy-related hematological and GI toxicities are common among Vietnamese breast cancer patients, and their development was associated with pre-chemotherapy GI microbiota. Our study suggests that maintaining healthy gut microbiota may be a potential preventive measure to reduce chemotherapy-induced toxicity. Further studies are needed to validate our findings and investigate the role of microbiota in long-term chemotherapy-induced toxicities as well as treatment efficacy among breast cancer patients. | |
