# Populations of triple negative and hormone receptor positive HER2 negative breast tumors share immune gene profiles

## TL;DR

Triple negative and hormone receptor positive HER2 negative breast tumors share similar immune gene profiles, suggesting immune activity is not subtype-specific.

## Contribution

The study reveals that immune-high signatures in breast tumors are not dictated by subtype but by fibroblast abundance differences.

## Key findings

- TN and HR+ HER2− tumors both have immune-high and immune-low subtypes.
- Immune-high TN tumors have more Th1/Th2 CD4+ T cells, while HR+ HER2− tumors have more fibroblasts.
- Fibroblast abundance in HR+ HER2− tumors correlates with worse outcomes.

## Abstract

In breast cancer, triple negative (TN) breast cancer has most responses to immune checkpoint inhibitor (ICI) therapy. Lymphocyte infiltrate does not impact prognosis in Hormone receptor positive HER2 negative (HR + HER2-) breast tumors and few HR + HER2− tumors respond to ICI. We contrasted immune-associated gene expression between 119 TN and 475 HR + HER2− breast tumors from The Cancer Genome Atlas (TCGA) and confirmed our findings in 299 TN and 1369 HR + HER2− breast tumors in the METABRIC database. TN and HR+ HER2− tumors grouped into immune-high or -low tumors, both subtypes were represented in the immune-high group. The largest difference between the immune-high TN and HR + HER2− tumors was TN tumors had more abundant Th1 and Th2 CD4+ T cells while HR + HER2− tumors had more abundant fibroblasts (log2FC > 0.3; p < 10×10−10). This suggests an immune-high signature is not dictated by breast cancer subtype, but fibroblast subsets associated with worse outcome were higher in the immune-high HR + HER2− tumors.