Background Unlike western countries, breast cancer tends to occur in older and postmenopausal female; in Taiwan, 40% of patients are younger than 50 years old and are mainly diagnosed in premenopausal women. Increasing evidence has demonstrated that microbiome-host interactions may contribute to breast cancer development and treatment in addition to genetic variations. Interestingly, current studies suggest the gut microbial community likely affects the risk for estrogen-related diseases in older adults. We aimed to explore the gut microbial profiles in regarding with menopausal status and elucidate whether the gut microbiomes and related function pathways were different in premenopausal and postmenopausal breast cancer patients in Taiwan. Methods A total of 70 healthy female controls (premenopausal/Pre-C, n=20; postmenopausal/Post-C, n=50) and 146 stage I/II breast cancer patients (premenopausal/Pre-BC, n=70; postmenopausal/Post-BC, n=76) were enrolled in our study. The microbial composition in fecal samples was analyzed using 16S rRNA amplicon sequencing (V3-V4 region) on the Illumina Miseq platform. The obtained data was analyzed using CLC Microbial Genomics Module (Qiagen, Germantown, MD, USA). Linear discriminant analysis effect size (LEfSe) and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) were analyzed with Galaxy/HutLab and Metagenomic Profiles (STAMP) software. Results Alpha diversity of the Shannon index was unexpectedly higher in Pre-BC when compared with that of Pre-C. Weighted beta-diversity with the principal coordinate analysis (PCoA) demonstrated that total microbial compositions were significantly different between Pre-C versus Pre-BC (p=0.001) and Post-C versus Post-BC (p=0.054). The Operational Taxonomic Units (OTUs) and Krona analysis showed that the abundance of Proteobacteria was significantly increased in both Pre-BC and Post-BC (p=0.011 and 0.017), whereas Bifidobacterium was significantly reduced in both Pre-BC and Post-BC1 (p<0.001 and 0.009) when compared with the matched controls, Pre-C and Post-BC. We further clarified the microbial markers based on the linear discriminant analysis effect size (LEfSe). As compared with Pre-C, Pre-BC had a much higher abundance of pathogens including Shigella, Clostridium, Haemophilus and others. The total microbial composition was also significantly different between Pre-BC and Post-BC (p=0.001). Intriguingly, the abundance of the microbiomes in alpha-Linolenic acid metabolism was reduced in Pre-BC when compared with Post-BC, whereas alpha-Linolenic acid metabolism were increased in both Pre-BC and Post-BC as compared with their matched controls. Conclusion Our results provide hints that, dysbiosis might be one of triggers or niches in contributing to Taiwan Pre-BC and might modulate multiple signaling pathways in relation to lipid metabolism and pathogen infections. The mechanisms underlying the link of specific gut microbiomes to Taiwan breast cancer require further investigations.

Citation Format: Ming-Feng Hou, Chih-Po Chiang, Yao-Tsung Yeh. The gut microbial signatures of premenopausal breast cancer in Taiwan [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS2-28.