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J. Zhao



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    MO16 - Prognostic and Predictive Biomarkers IV (ID 97)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
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      MO16.03 - Cytoplasmic ERβexpression predicts poorly efficacy and survival of EGFR-TKI in EGFR mutant NSCLC (ID 2563)

      16:15 - 17:45  |  Author(s): J. Zhao

      • Abstract
      • Presentation
      • Slides

      Background
      Estrogen receptor pathway has been reported to be interacted with epidermal growth factor receptor (EGFR) signal pathway. This study focused on the impact of intracellular ERβ localization (cytoplasmic or nuclear) on the efficacy of EGFR-TKI.

      Methods
      Tumor tissue specimens from 149 stage IV NSCLC patients treated with EGFR-TKI were analyzed using immunohistochemistry (IHC) for ER expression (ERαorβ) and their associations with clinicopathological variables and clinical outcomes. Significance of cyto-ERβ expression was further examined in NSCLC cell lines.

      Results
      The expression of ERα and ERβ was detected in 15% and 28.9% of the patients, respectively. Cyto-ERβ positive cases showed shortened progression free survival (PFS) compared with cyto- ERβ negative ones (3.1 months vs. 7.3 months, p=0.061). In the subgroup with concurrent EGFR mutation, the differences of PFS were enlarged with significant statistics (4.7 months vs. 10.9 months, p=0.042). COX’s proportional hazard model showed that female, EGFR mutation and c- ERβ negative expression were independent predictive factors for PFS. PC-9 cells present ERβ in cytoplasma as well as nucleus. Estrodial (E2) induced PC-9 cells moderately resistant to erlotinib with a 3-fold increase of IC50, and the resistance can be reversed by ER blocker (fulvestrant) or siRNA directed to ESR2. The function of E2 was accomplished by nongenomic activation (MAPK phosphorylation) caused by E2 via cyto- ERβ. Combination therapy with erlotinib and fulvestrant turned out to be far more effective than either treatment alone in PC-9 cells. Furthermore, 2 patients harboring both EGFR mutation and cyto-ERβ expression underwent PD of EGFR-TKIs, and re-obtained disease control after receiving combined EGFR-TKIs with fulvestrant.

      Conclusion
      Cyto-ERβ expression may predict relatively poor efficacy to EGFR-TKI compared with non- cyto-ERβ expression in NSCLC patients harboring EGFR mutation.

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