Abstract B23: The mammary tissue microbiome in breast cancer development

Abstract

Abstract Introduction: Breast cancer is the most prevalent type of cancer among women (other than some nonmelanoma skin cancers), with approximately one in eight women diagnosed with breast cancer during their lifetime. The mammary tissue microbiome has recently been characterized, and shifts in the abundance of mammary tissue bacterial taxa have been associated with benign and malignant breast tumors. This suggests particular bacterial taxa as oncogenic and key in driving breast cancer development. However, these studies utilized mammary tissue obtained from breast reduction or enhancement surgery as healthy control tissue, which has significant histologic abnormalities compared to tissue from normal healthy donors. The Susan G. Komen Tissue Bank (KTB) at the Indiana University Simon Cancer Center (IUSCC) is a unique and precious repository of normal breast tissue, ideal for compositional and functional analyses of the mammary tissue microbiome. We have also identified a subset of women who donated healthy tissue to the KTB and later developed breast cancer. This provides us with a rare opportunity to study shifts in the mammary microbiome composition that may preclude breast cancer development. Our research objective is to compare the composition of the mammary microbiome in healthy and prediagnostic tissue to that of cancerous tissue. Methods: Our cohort comprises four tissue subsets: healthy (n = 50), prediagnostic (n = 15), adjacent normal (n = 50), and tumor (n = 50) selected from the KTB and IUSCC Tissue Banks. DNA was isolated from all 165 tissue samples. DNA from three of these samples, two positive controls, and two negative controls was submitted for Illumina Miseq paired-end sequencing of the V4 region of the 16S gene at the University of California, Davis Host Microbe Systems Core Lab. Results/Conclusions: The breast tissue samples display microbiome compositions dominated by three phyla: Proteobacteria, Firmicutes, and Bacteroidetes. Negative controls displayed fewer than 10 reads and positive controls yielded accurate percentages of several difficult-to-lyse bacteria. In January 2020, all 165 DNA samples will be submitted for 16S rRNA metagenomic sequencing for analysis of the microbiome composition among the four tissue subsets. We will use multivariate linear modeling to adjust for clinical factors such as age, BMI, and menopausal status and to determine if microbiome composition is modified by cancer status. This work will be fundamental in characterizing the composition of the healthy mammary tissue microbiome and identifying microbial determinants of breast cancer. Citation Format: Jaelyn Gabel, Courtney Hoskinson, Annie Kump, Karin B. Michels, Natascia Marino, Leah T. Stiemsma. The mammary tissue microbiome in breast cancer development [abstract]. In: Proceedings of the AACR Special Conference on the Microbiome, Viruses, and Cancer; 2020 Feb 21-24; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2020;80(8 Suppl):Abstract nr B23.