The Landscape of the Intestinal Microbiome Amongst Patients with Newly Diagnosed Invasive Breast Cancer (BC) and Ductal Carcinoma in Situ (DCIS).

563 Background: The gut microbiota has been recognized as a master modulator of the immune system and has been associated with outcomes among cancer patients. There is a paucity of knowledge surrounding the landscape of the gut microbiome in BC pts with invasive and non-invasive disease or how it can affect response to systemic therapy. We sought to define the landscape of the gut microbiome in invasive BC and DCIS patients and evaluate differences by subtype. Methods: Prospective clinical trials (NCT04425018 and NCT02752685) and institutional registries enrolling patients with DCIS and stage I-III invasive BC at a single institution collected baseline stool samples prior to initiation to systemic therapy. Samples underwent whole-genome metagenomic sequencing (2 x 150 bp, Illumina NovaSeq) and data were processed into taxonomic (species) abundances using MetaPhlAn4. Associations between metadata and ecological features (alpha and beta diversity) were tested with ANOVA and PERMANOVA. Individual species were tested for association as univariable linear models on normalized, log-transformed relative abundances, with p-values FDR adjusted for multiple comparisons, using MaAsLin2. Results: 278 baseline samples were analyzed: 43 DCIS, 101 TNBC, 54 HR+/HER2-, 24 HR-/ HER2+, 37 HR+/HER2+. Most patients were age >50 (71%) and white (83%). No significant differences were observed in baseline stool microbiomes between invasive BC and DCIS pts for alpha (p = 0.185) or beta (p= 0.476) diversity, nor for individual microbial species. HR+/HER2+ BC had a unique microbiome profile with significantly different beta diversity (p = 0.005), with six associated species (q < 0.25). No other associations with invasive BC subtype were observed. Bacteroides ovatusabundance was significantly different between Stage I and III BC pts (p = 0.0003, q = 0.116). Several taxa were associated with age at diagnosis. Conclusions: No significant differences were observed in baseline stool microbiome composition between patients with invasive breast cancer and DCIS. HR+/HER2+ BC microbiome composition was distinct from other subtypes, and a significant difference in Bacteroides ovatus abundance emerged between Stage I and III pts, suggesting potential microbial associations with cancer subtypes and progression.