ETS transcription factor ESE-1/Elf3 is an independent prognostic factor of survival in HR⁺HER2⁺ breast cancer patients.

PURPOSE:The ETS transcription factor ESE-1 has been shown to be important in HER2⁺ breast cancer and ESE-1 mRNA expression has been shown to associate with prognostic outcomes in the HER2⁺ subtype, as well as in ER⁺, HER2⁺ luminal B patients. However, the clinical significance of ESE-1 protein expression remains unknown. The purpose of the current exploratory study is to evaluate the prognostic value of ESE-1 protein expression in molecular breast cancer subtypes with special emphasis on hormone receptor positive HER2⁺(HR⁺ HER2⁺) and the HER2 positive (HER2⁺-only) breast cancer patients. METHODS:We developed a mouse monoclonal anti-ESE-1 antibody, verified its specificity, epitope, and used immunohistochemical staining to assess ESE-1 expression in an IBC approved archive of 957 breast tumor samples. Using Pearson product correlation, contingency analysis, and long rank P value testing, we analyzed the association of ESE-1 expression with clinicopathological features and survival outcomes in HR⁺HER2^-; HR⁺HER2⁺; HR^- HER2^- (Triple negative) and HR^-HER2⁺ (HER2 subtype) patients. RESULTS:ESE-1, nuclear or cytoplasmic, was not significantly associated with survival outcomes in HR⁺HER2^-, triple-negative, or HER2⁺-only breast cancer patients. However, high nuclear ESE-1 was associated with poor survival outcomes in hormone receptor positive (ERα⁺, PR⁺) HER2⁺ patients and was an independent prognostic marker for that group. CONCLUSIONS:This study provides evidence for prognostic significance of nuclear ESE-1 in ERalpha positive breast cancers patients also positive for HER2 indicating that crosstalk between ERalpha and ESE-1 in HER2⁺ tumors could be important for prognostic outcomes. Further studies regarding the nature of interaction between ESE-1 and ERalpha in these tumors are warranted.

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