Positive Expression of Insulin-Like Growth Factor-1 Receptor Is Associated with a Positive Hormone Receptor Status and a Favorable Prognosis in Breast Cancer

Abstract

PurposeInsulin-like growth factor 1 receptor (IGF-1R) is commonly expressed in primary breast cancers. Understanding the role of IGF-1R signaling in the different subtypes of breast cancer is important because each subtype has a different outcome and requires different treatment modalities. However, the precise biological significance of IGF-1R expression in cancer cells is still unclear. In this study, we examined the expression of IGF-1R in the different molecular subtypes of breast cancer. The effects of IGF-1R expression on the survival rates and outcomes of breast cancer were also examined.MethodsIGF-1R expression was evaluated immunohistochemically in tissue microarray blocks constructed from 1,198 invasive breast cancer samples collected from six medical institutions. IGF-1R expression was interpreted according to the human epidermal growth factor receptor 2 (HER2)/neu immunohistochemistry scoring system. Scores of 2+ and 3+ were considered positive.ResultsPositive IGF-1R expression was observed in 65.4% of invasive breast cancer samples. IGF-1R expression was detected in all cancer subtypes (luminal A, 84.4%; luminal B, 75.9%; HER2, 21.2%; triple-negative, 46.6%) and was found to be associated with a positive hormone receptor status and the absence of HER2 amplification (p<0.001). Positive IGF-1R expression was significantly associated with high survival rates (p=0.014). However, a multivariate analysis revealed that the expression levels of IGF-1R did not achieve statistical significance. In the triple-negative cancer subtype, IGF-1R expression was found to be associated with a lower disease-free survival rate (p=0.031).ConclusionPositive IGF-1R expression is associated with a favorable prognosis in breast cancer. IGF-1R is frequently expressed in the luminal A/B subtypes of breast cancer, and its expression is related to the hormone receptor status.

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

“…Recently, IGF-1R is considered as one promising biomarker for overcoming resistance of HER-2 positive breast cancer. However, previous studies have demonstrated contradictory results regarding a potential role of IGF-1R in breast cancers [17,18,22]. In this study, no definitive roles of IGF-1R expression were shown in HER-2 positive breast cancers, however, in the subgroup analysis of HRs-positive diseases, IGF-1R expression was moderately correlated and might be a potential biomarker for overcoming resistance to HER-2 directed therapy.…”

“…In this study, no definitive roles of IGF-1R expression were shown in HER-2 positive breast cancers, however, in the subgroup analysis of HRs-positive diseases, IGF-1R expression was moderately correlated and might be a potential biomarker for overcoming resistance to HER-2 directed therapy. In a recent study analyzed more than 1,100 patients, IGF-1R expression was frequently expressed in the luminal A/B subtype tumors and positive correlation of IGF-1R with prognosis was demonstrated [18]. Phase II clinical trials of IGF-1R inhibitors are ongoing and these trial results will give a clue regarding the role of IGF-1R and the efficacy and safety of IGF-1R inhibitors in HER-2 positive breast cancer [19].…”

“…The lowest proportion of one-thirds was determined in HER-3 expression. Previous studies have shown various positive rates of EGFR, HER-3, HER-4, and IGF-1R expression among HER-2 positive breast cancers, which ranged from 18% to 56%, 9% to 91%, 18% to 59%, and 26% to 44%, respectively [13][14][15][16][17][18]. Although these wide frequencies of positive growth factor receptors family expression may be partly caused by the different characteristics of study cohorts or the lack of standard methodology among reports, the present study also demonstrated similar results.…”

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

“…IGF-1R expression in other researches have a wide range of value. Shin et al (2014) reported only IGF-1R positive membranous expression which they found as much as 65,4% (17). Yerushalmi et al (2012) also reported IGF-1R positive membranous expression in total 46% cases (35).…”

“…Many researches have reported that insulin-like growth factor type-1 receptor (IGF-1R) may have role in anti-HER-2 resistancy. IGF-1R expression have been reported high in many malignancies including breast carcinoma (17). IGF-1 ligand binds IGF-1R to initiate downstream signaling pathway of phosphatidylinositol 3-kinase (PI3K)-Akt which have role in cell survival and mitogen-activated protein kinase (MAPK) which have role in cell proliferation (18).…”