Conflicting roles of expression by subtypes in breast cancer.

Epidermal growth factor receptor () is one of the receptors that belong to the epidermal growth factor family of receptor tyrosine kinases (ErbBs). Several malignancies including breast cancer that express EGFR have poor prognosis. Our study examined the EGFR expression among 5176 breast cancer patients from GSE96058 and METABRIC cohorts and the contribution of tumor immune microenvironment in different subtypes. We found that among different breast cancer subtypes, expression in TNBC was the highest compared to other subtypes. high ER-positive/HER2-negative breast cancer had significantly higher survival compared to low ER-positive/HER2-negative breast cancer. It was also associated with high level of intratumor heterogeneity and homologous recombination defects (HRD). This group was also enriched in immune-related gene sets. On the other hand, low tumor was enriched in cell proliferation-related gene sets. However, these findings were not observed in . Interestingly, there was a greater infiltration of anti-cancer immune cells in high ER-positive/HER2-negative breast cancers, while, TNBC with higher EGFR expression had lower fraction of immune cells along with low level of cytolytic activity. Tumor cells have significantly higher expression compared to immune cells in single cell sequencing data. There was higher expression of immune checkpoint molecules in high ER-positive/HER2-negative breast cancer but lower expression in TNBC. High metastatic tumor was significantly associated with worse survival, but no association with infiltrating immune cells was observed. Our study shows that higher expression in ER-positive/HER2-negative breast cancer is associated with improved outcomes and an anti-cancer immune microenvironment.