IGF-1R Expression has More Potential Proliferation Effect in Invasive Breast Carcinoma Of No Special Type Compared to HER-2 Expression

Abstract

About 75% of breast carcinoma is invasive carcinoma of no special type (NST) and between 20%-30% of breast carcinoma is HER-2 positive. HER-2 overexpression now is a predictive factor for targeted therapy with anti-HER-2 agent like trastuzumab (herceptin). However, primary (de novo) resistance with trastuzumab occured in 65% patients and secondary resistance occured in 70% patients who have had good initial response. IGF-1R expression have been reported high in many malignancies including breast carcinoma. Researches have showed that IGF-1R signaling pathway have a crosstalk with HER-2 signaling pathway and was thought to become one of resistance mechanism in anti-HER-2 targeted therapy. This research was a retrospective observational cross-sectional study with a total 55 samples. Expression of IGF-1R and HER-2 was evaluated immunohistochemically. A strong positive IGF-1R cytoplasm and membranous expression was found in 18,2% and 34,5% cases, respectively. HER-2 expression was positive in 23,6% cases. IGF-1R cytoplasm expression was correlated significantly with mitosis count (p=0.049). There was no correlation between IGF-1R membranous expression with mitosis count (p=0,641). There was no correlation between IGF-1R membranous and cytoplasm expression with histological grade (p=1,000) and there was no correlation between HER-2 expression with mitosis count (p=0,495) and histological grade (p=1,000). IGF-1R expression has more potential effect in mitosis compared with HER-2 expression. Inhibition it's signaling pathway may have therapeutic value in breast carcinoma. Combination therapy of anti-HER-2 with anti-IGF-1R could overcome resistancy of trastuzumab in HER-2 positive breast carcinoma.