Abstract 2725: Immune-cell profiling in breast cancer patients by race and triple negative breast cancer status
Authors: Hu Xiaozhuang , Collado-Mesa Fernando , Yang George R. , Reis Isildinha M. , Hu Jennifer J. 
Published: July 2021

Breast cancer is the most frequently diagnosed cancer and the second leading cause of cancer-related death among American women. Underserved minorities suffer from higher mortality rates and a higher prevalence of triple-negative breast cancer (TNBC). Previous studies showed that African Americans (AA) have a higher risk for TNBC, advanced tumor, pro-inflammatory tumor microenvironment, and worse survival. Immune responses and inflammatory processes play critical roles in cancer initiation, progression, and suppression. Therefore, this study was designed to investigate the complex interplay among the tumor, microenvironment, and immune response by race and TNBC status. Tumor biopsy samples from 96 breast cancer cases were used for the NanoString PanCancer IO 360 Gene Expression Panel analysis. The panel is a 770 gene Code Set that is designed for profiling tumor biopsies and characterizing gene expression patterns associated with the tumor, the immune response, and the microenvironment that shape tumor-immune interactions. After quality control for 20 reference genes, gene expression data from 93 samples were used for subsequent data analysis with nSolver 4.0 to calculate expression changes, pathway mapping based on annotations, sample clustering (heat maps), and 14 immune cell type abundance signatures. Then we conducted a Student's t-test and ANOVA for comparison of immune cell types by patient demographics and clinical characteristics using SAS University Edition 2019. In 10 TNBC and 83 non-TNBC, the expression of 12 genes was significantly different, 4 were higher and 8 were lower in TNBC (False Discovery Rate adjusted p&lt;0.05). AA patients had significantly higher B cells (p=0.02), T cells (p=0.03), macrophages (p=0.02), CD45 (p=0.02), and Treg cells (p=0.04) than white patients. Patients diagnosed at a young age had significantly lower neutrophil counts (p=0.02). Nonsmokers had significantly higher mast cell scores than smokers (p=0.03). Mast cells were significantly lower in ER-negative (p&lt;0.01), PR-negative (p&lt;0.01), and TNBC (p&lt;0.01) patients than ER-positive, PR-positive, and non-TNBC patients. Our study results suggest that gene expression and immune cell types are different by race and TNBC status. Future data analysis will focus on 18-gene tumor inflammation signature, 15+ proprietary gene expression signatures, and 14 immune cell type abundance signatures with a single sample and dataset analysis report, and automatic predictive algorithm training. With the recent FDA accelerated approval of PD-L1 inhibitor atezolizumab as a treatment for PD-L1-positive metastatic TNBC, the NanoString PanCancer IO 360 panel may provide the capability to both discover new biomarkers and create potentially predictive signatures for immunotherapies, which in turn may help improve minority health and reduce survival disparities.

Citation Format: Xiaozhuang Hu, Fernando Collado-Mesa, George R. Yang, Isildinha M. Reis, Jennifer J. Hu. Immune-cell profiling in breast cancer patients by race and triple negative breast cancer status [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2725.