Abstract PS3-01-16: Gut microbial dysbiosis associates with the early-onset breast cancer in BRCA mutation carriers

Abstract Germline BRCA mutation carriers face a high risk of developing breast cancer, yet individual risk and age of onset vary significantly, influenced by both genetic and environmental factors. The gut microbiota is crucial for host health, regulating immunity, metabolism, and endocrine functions. Dysbiosis—an imbalance of gut microbiota—has been linked to diseases including cancer. We aimed to investigate whether specific gut microbes influence breast cancer risk in BRCA mutation carriers and to explore the underlying mechanisms. First, we studied 27 BRCA mutation carriers with early-onset breast cancer (60 years) without cancer. Fecal microbiota were analyzed using full-length 16S rRNA sequencing. The linear discriminant analysis (LDA) effect size (LEfSe) analysis showed that the Eggerthella lenta (E. lenta) and Dorea longicatena (D. longicatena) were the most significantly enriched bacteria in feces of the mutation carriers with early-onset breast cancer, compared to those in the old carriers without breast cancer. As these two bacteria are more common in older individuals, their presence in younger cancer patients suggests an association with cancer, independent of age. Second, we expanded the study to 102 BRCA mutation carriers (54 BRCA1, 48 BRCA2), 64 of whom had breast cancer. Mutation carriers with fecal E. lenta had a significantly earlier age of breast cancer than those without it (median age: 42.2 vs. 52.8 years-old, p