Abstract 3041: Gut microbiome in association with chemotherapy-induced toxicities among breast cancer patients
Authors: Nguyen Sang M. , Tran Huong T. , Long Jirong , Shrubsole Martha J. , Cai Hui , Yang Yaohua , Cai Qiuyin , Tran Thuan V. , Zheng Wei , Shu Xiao-Ou 
Published: April 2023

Abstract
Growing evidence suggests that gut microbiota may influence chemotherapy efficacy. However, little research has been done on the relationship between the gut microbiome and chemotherapy-induced toxicity. We conducted a prospective study among 301 chemotherapy-treated breast cancer patients who were recruited into the Vietnamese Breast Cancer Study and had a pre-chemotherapy stool sample collected. The stool collection included 134 pre- and 167 post-breast cancer surgery samples. Chemotherapy-induced toxicities during the first-line treatment were captured via medical chart reviews and patient-reported outcomes and graded using the National Cancer Institute Common Toxicity Criteria of Adverse Events classification. Gut microbiome composition was measured by shotgun metagenomic sequencing. Associations of pre-chemotherapy gut microbial diversity, taxa abundance, and microbial metabolic pathways with severe (i.e., grade ≥ 3) hematological and gastrointestinal (GI) toxicities were evaluated via multivariable logistic regression. A substantial proportion of study participants experienced severe hematological (39.2%) and GI (13.3%) toxicities. Reduction in α- and β-diversities (P&lt;0.001) and significant differences in the relative abundance of nearly 40% of 2,864 investigated taxa (PFDR &lt;0.1) were observed between stool samples collected from pre-and post-surgery. Surgery is always followed by antibiotic prophylaxis in Vietnam. High α-diversity (P&lt;0.05) and high abundances of 29 taxa (most of them from Lachnospiraceae, Oscillospiraceae, and Ruminococcaceae; PFDR &lt;0.1) among samples before surgery and neoadjuvant chemotherapy (n=134) were associated with a significantly reduced risk of severe hematological toxicity and neutropenia. In addition, 47 taxa from Bacteroidaceae, Lachnospiraceae, Sporanaerobacteraceae, and Fusobacteriaceae were significantly associated with an increased risk of severe neutropenia in this sub-population (PFDR &lt;0.1). Moreover, we found that relative abundances of microbial metabolic pathways involved in the reductive TCA cycle I, phosphatidylglycerol biosynthesis I and II, and superpathway of phospholipid biosynthesis I were associated with an increased risk of severe GI toxicity, particularly nausea/vomiting; these associations did not differ by time of stool sample collection (P &lt;0.05). Conversely, high abundances of microbial metabolic pathways involved in lactose and galactose and L-proline biosynthesis II (from arginine) were associated with a reduced risk of severe GI toxicity (P &lt;0.05). In conclusion, the pre-chemotherapy gut microbial composition was associated with developing severe chemotherapy-induced hematological and GI toxicities among Vietnamese breast cancer patients. Our study suggests that maintaining healthy gut microbiota may be a potential preventive measure to reduce chemotherapy-induced toxicity.
Citation Format: Sang M. Nguyen, Huong T. Tran, Jirong Long, Martha J. Shrubsole, Hui Cai, Yaohua Yang, Qiuyin Cai, Thuan V. Tran, Wei Zheng, Xiao-Ou Shu. Gut microbiome in association with chemotherapy-induced toxicities among breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3041.