Distinct tumor microbiome profiles in triple negative breast cancer compared to other breast cancer subtypes: A pilot study

Background: Emerging evidence suggests that the tumor microbiome may influence breast cancer biology and therapeutic responses. However, few studies have characterized microbial differences across breast cancer subtypes, particularly triple-negative breast cancer (TNBC), which tends to have poor prognosis and limited targeted therapies, compared with other subtypes. We conducted a pilot study to compare the microbiome in TNBC versus other subtypes. Methods: DNA was extracted from 25 formalin-fixed paraffin-embedded (FFPE) tumor tissues, including 4 TNBC cases and 21 non-TNBC cases. 16S rRNA gene sequencing was performed to characterize bacterial composition. Relative abundance was analyzed at multiple taxonomic levels. Differential abundance between TNBC and other subtypes was evaluated using linear regression. Results: Distinct microbial signatures were observed between TNBC and other subtypes. At the phylum level, TNBC tissues were enriched in Fusobacteriota compared with non-TNBC tissues ( p value=0.03). At the family level, TNBC tissues showed higher relative abundance of Dermacoccaceae , Fusobacteriaceae , and Rikenellaceae , and lower abundance of Oscillospiraceae (p values<0.05 ) . At the genus level, TNBC tumors were enriched in Dermacoccus , Rothia , and Alistipes , while UCG-002 was reduced compared to other subtypes ( p values <0.05). Conclusions: This pilot study reveals distinct microbial composition in TNBC tissues compared with other breast cancer subtypes, characterized by enrichment of Fusobacteriota and specific genera such as Dermacoccus and Rothia . These findings suggest potential microbiome-mediated mechanisms contributing to TNBC biology and warrant validation in larger, well-annotated cohorts.