Abstract P5-03-01: Conflicting roles of <i>EGFR</i> expression by subtypes in breast cancer
Authors: Masanori Oshi, Shipra Gandhi, Yoshihisa Tokumaru, Rongrong Wu, Li Yan, Akimitsu Yamada, Takashi Ishikawa, Itaru Endo, Kazuaki Takabe
Journal: Cancer Research (2022)

Abstract Epidermal growth factor receptor (EGFR) is one of the receptors that belongs 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 multiple independent breast cancer cohorts and its contribution to tumor immune microenvironment in different subtypes. We found that, EGFR expression in triple negative breast cancer (TNBC) was the highest among breast cancer subtypes in GSE96058 and METABRIC cohorts when compared to other subtypes (both p &amp;lt; 0.001), which is in agreement with the existing literature. High EGFR expression was significantly associated with improved survival in ER-positive/HER2-negative breast cancer in both cohorts (both p &amp;lt; 0.001) and also significantly associated with high level of intratumor heterogeneity and homologous recombination deficits (HRD) (both p &amp;lt; 0.001) in the TCGA cohort. Furthermore, high EGFR expression tumor enriched not only several pro-cancer-related gene sets, but also immune-related gene sets, including Allograft rejection, inflammatory response, IL2/STAT5 signaling, IL6/JAK/STAT3 signaling, coagulation and complement pathway in both cohorts. On the other hand, low EGFR tumor enriched cell proliferation-related gene sets, including E2F targets, G2M checkpoint MYC targets v1 and v2, and DNA repair, which may explain the observed worse survival (all normal enrichment score &amp;lt; -0.50). However, these findings were not observed in TNBC. Interestingly, high EGFR ER-positive/HER2-negative breast cancers were infiltrated with anti-cancer immune cells (CD8+ T cell, CD4+ T cell, and dendritic cell), and associated with high level of cytolytic activity (CYT) (p &amp;lt; 0.001). On the other hand, a lower fraction of immune cells was observed in high EGFR TNBC along with low level of CYT (p &amp;lt; 0.001). In the single cell sequence data, tumor cells have significantly higher EGFR expression compared to immune cells (p &amp;lt; 0.001). High EGFR expression among ER-positive/HER2-negative breast cancer was significantly associated with higher expression of immune checkpoint molecules (PD-1, PD-L1 and PD-L2, CTLA4, IDO1, and BTLA; all p &amp;lt; 0.001), while, on the other hand, there was lower immune checkpoint molecule expression in high EGFR TNBC. Finally, high EGFR metastatic tumor was associated with worse survival, but there was no association with infiltrating immune cells. In conclusion, EGFR expression was found to have different characteristics depending on breast cancer subtype. Especially, high EGFR ER-positive/HER2-negative breast cancer was significantly associated with better survival and immunity in tumor immune microenvironment. Citation Format: Masanori Oshi, Shipra Gandhi, Yoshihisa Tokumaru, Rongrong Wu, Li Yan, Akimitsu Yamada, Takashi Ishikawa, Itaru Endo, Kazuaki Takabe. Conflicting roles of EGFR expression by subtypes in breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-03-01.