Abstract 5927: A comparison of the gut microbiome in the context of body mass index in patients with and without breast cancer

Abstract Background: Through diverse interactions with systemic immunosurveillance and metabolism, the gut microbiome is an important factor in the development and treatment of solid tumors including breast cancer (BC). The gut microbiome is also implicated in elevated body mass index (BMI), which is a well-established risk factor for the development of BC. This study determined associations between gut microbiome diversity and BC, adjusting for BMI. Methods: Stool samples were collected from 38 patients with newly-diagnosed BC and 43 age-matched non-cancer controls. Data obtained from 16S rRNA sequencing of fecal samples were clustered into amplicon sequence variants using DADA2. Diversity measures were calculated using vegan and phyloseq, and the statistical differences were compared using t-test or Wilcoxon rank-sum tests. Data were agglomerated at the family level for differential abundance analyses, which were performed with DESeq2. Results: The majority of BC cases observed were stage I (55.26%), hormone-receptor positive (70.97%), and detected during routine screening (68.42%). Mean BMI was greater among patients diagnosed with BC than controls (mean BMI cases: 27.9, controls: 25.23, p=0.04). Alpha diversity measured by the Shannon, Inverse Simpson and Pielou indices was lower in the BC cohort compared with the control cohort (p = 0.02, 0.01, and 0.05, respectively). Beta diversity by non-metric multidimensional scaling on Bray-Curtis distance did not differ between cases and controls (p = 0.74). Five versus seven families and orders were differentially abundant when the analysis was adjusted for BMI versus not, respectively (Table). Conclusion: Differential abundance analysis results differed with and without BMI adjustment, indicating that adjusting for this potentially confounding variable is relevant for BC microbiome studies. BMI should be considered an adjusting variable in studies of the gut microbiome in BC. Negative values for log 2 fold change indicate organisms with greater abundance in controls. Result of DESeq2 analysis without BMI adjustment Family Log 2 Fold Change P adjusted Hungateiclostridiaceae -1.115 0.0034 Enterobacteriaceae 2.925 <0.0001 Fusobacteriaceae 2.043 <0.0001 Lactobacillaceae -1.097 0.0063 Selenomonadaceae 0.985 0.0004 Order Gastranaerophilales -2.653 <0.0001 Flavobacteriales -1.462 0.0002 Result of DESeq2 analysis with BMI adjustment Family Log 2 Fold Change P adjusted Hungateiclostridiaceae -1.273 <0.0001 Enterobacteriaceae 2.379 <0.0001 Selenomonadaceae 1.015 <0.0001 Order Gastranaerophilales -1.838 <0.0001 Flavobacteriales -1.460 <0.0001 Citation Format: Brie Chun, Duygu Altinok Dindar, Keaton Stagaman, Amy Palma, Erin Dahl, Kristin Kasschau, Shaun M. Goodyear, Zahi I. Mitri, Thomas Sharpton, Lisa Karstens, Zhenzhen Zhang. A comparison of the gut microbiome in the context of body mass index in patients with and without breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5927.