Expression of growth factor receptor family before and after targeted therapy in human epidermal growth factor receptor-2 positive breast cancer tissues

Abstract

Purpose: This study aimed to compare expression of human epidermal growth factor receptor (HER) family and insulin-like growth factor- 1 receptor (IGF-1R) before and after targeted therapy in HER-2 positive breast cancers. Methods: Epidermal growth factor receptor (EGFR), HER-3, HER-4, and IGF-1R were immunohistochemically determined using pairwise archives tumor blocks of 28 patients received chemotherapy and HER-2 directed therapy between January 2007 and December 2011. Of them, 5 good responders achieved a pathologic complete response after neoadjuvant therapy and 23 poor responders experienced disease progression or metastasis even HER-2 targeted therapy. Expression of biomarkers was compared using chi-square test. Results: Stage II, III, and IV was 14 (50.0%), 11 (39.3%), and 3 (10.7%) patients, respectively. Hormone receptors-positive tumors were 15 (53.6%) patients and 9 (32.1%) patients received tyrosine kinase inhibitors with or without trastuzumab. Positive expression of initial EGFR, HER-3, HER-4, and IGF-1R was determined in 15 (53.6%), 11 (39.3%), 22 (78.6%), and 14 (50.0%) patients, respectively. Although there was no statistical significance, good responders showed a higher proportion of positive HER-3 expression. Among 23 poor responders, growth factor receptors family expression showed a trend of concordant results, however, unpredictively certain patients demonstrated discordant results between before and after targeted therapy. Conclusion: Unpredicted correlation of growth factor receptors family expression suggested that complex and personalized resistance mechanisms may be involved to HER-2 directed therapy. However, HER-3 expression might be associated with responsiveness to HER-2 targeted therapy. It would be important to develop diagnostic and therapeutic strategies for overcoming resistance to HER-2 targeted therapy.