Abstract 756: Differences in composition, diversity, and function of the fecal microbiota of post-menopausal breast cancer patients compared to healthy, age-matched controls
Authors: Kabbej Nadia , Ashby Frederick , Atencio Erika , Rosenkrantz Erinn , Day Dominique , Dang Khloe , Gauthier Josee , Newsome Rachel , Sommerville John , Naas Taqwa , Gharaibeh Raad , Jobin Christian , Quevedo Amira , Heldermon Coy D. 
Published: March 2024

Abstract
Gut microbiota are a community of organisms that colonize the intestinal tract with essential roles in immune function, gut epithelial integrity, and metabolite production. Dysbiosis occurs when the gut microbiota environment is negatively altered causing detrimental changes to these functions, which may predispose an individual to breast cancer development. To understand the relationship between dysbiosis and breast cancer development, fecal microbiota samples were collected from 27 post-menopausal breast cancer patients of varying hormone receptor statuses (ER+HER2-, ER+Her2+, ER-HER2+, or ER-Her2-) prior to starting chemotherapeutic treatment. Samples were compared to 25 healthy controls, and all samples underwent 16srRNA sequencing. Samples from breast cancer patients and control groups were compared for significant differences (P&lt;.05) in alpha (within sample) and beta (between sample) diversity. Using the Shannon Index and Generalized Least Squares Model, significant differences in alpha diversity were identified between all breast cancer types vs. controls (P=.0104), and between ER+HER2- breast cancer vs. controls (P=.00153). Healthy controls exhibited a higher mean Shannon Index than breast cancer patients, thus higher within sample diversity. Using principal coordinate analyses, significant differences in beta diversity were identified between all breast cancer types vs. controls (P = .01199), and ER+HER2- breast cancer vs. control (P = .008991). Further analyses identified significant taxa of microbiota with functions related to breast cancer development and progression. Of note, Lachnoclostridium, a genus of bacteria that can produce β-glucuronidase, which can deconjugate estrogen, was increased in all breast cancer types and ER+HER2- breast cancer when compared to controls. Deconjugation of estrogen can cause elevated blood estrogen levels, potentially increasing Estrogen Receptor binding in hormone-receptor-positive breast cancer. Additionally, Akkermansia, a genus implicated in gut barrier dysfunction, was decreased in ER+HER2- patients, while Parvimonas, a tumorigenic cell-cycle regulator, was increased. Elucidating if these effects are causative or reactionary may have important implications for understanding breast cancer etiology. Samples are currently undergoing additional metagenomic analyses using long-read sequencing to identify specific bacteria, viruses, fungi, parasites, and phages that may be contributing to dysbiosis. Overall, this study is the first, to our knowledge, to employ short and long-read sequencing to the fecal samples of untreated postmenopausal breast cancer patients. We provide mechanistic insight into the relationship between microbiota and breast cancer development, with the intent of informing future patient screening and prevention.
Citation Format: Nadia Kabbej, Frederick Ashby, Erika Atencio, Erinn Rosenkrantz, Dominique Day, Khloe Dang, Josee Gauthier, Rachel Newsome, John Sommerville, Taqwa Naas, Raad Gharaibeh, Christian Jobin, Amira Quevedo, Coy D. Heldermon. Differences in composition, diversity, and function of the fecal microbiota of post-menopausal breast cancer patients compared to healthy, age-matched controls [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 756.