Although
tamoxifen is the most common and effective
therapy for treatment of
estrogen receptor-α (ER-α)
breast cancer patients, resistance of endocrine
therapy occurs, either de novo or acquired during
therapy. Here, we investigated the clinical value of
epidermal growth factor receptor (EGFR) in
tamoxifen-resistant (TamR) patients and the differential effect of EGFR inhibitors,
neratinib and
gefitinib, on TamR
breast cancer cell model. The morphology of TamR MCF7 cells showed mesenchymal phenotypes and did not induce cell death by
tamoxifen treatment compared with tamoxifen‑sensitive (TamS) MCF7 cells. In addition, mesenchymal marker
proteins, including
N-cadherin (N-cad),
fibronectin (FN), and Slug, significantly increased in TamR cells. In contrast, ER-α and
E-cadherin (E-cad) were greatly decreased. We also found that the levels of EGFR and HER2 expression were increased in TamR cells. Furthermore, we observed that EGFR expression was directly involved with poor prognosis of
tamoxifen-treated
breast cancer patients using the GSE1378 date set. Thus, we treated TamR and TamS cells with EGFR inhibitors,
neratinib and
gefitinib, respectively. Interestingly,
neratinib induced apoptotic cell death of TamR but not
gefitinib. Cleaved PARP-1 expression was also increased by
neratinib treatment in TamR cells. Therefore, we suggest that
neratinib may be a potential therapeutic
drug for treating TamR
breast cancer.