Insulin-like growth factor receptor 1(IGFIR) is overexpressed in a subset of triple negative breast cancers

Abstract Insulin-like growth factor receptor 1 (IGF-1R) has a key regulatory role in malignancy and is the target of several drugs currently tested in clinical trials. Few studies have shown that IGF-IR expression is associated with estrogen receptor positive breast cancer. However, there are no systematic studies of IGF1R expression in triple negative breast carcinoma (TNBC). The aim of this study was to evaluate IGF1R protein expression and gene amplification in TNBC. Material and Methods: Ninety-seven TNBC (73 from Caucasian and 24 from African American women) were stained with anti-IGF1R antibody (clone G11, Ventana Medical Systems, Tucson, AZ, USA). IGF1R protein expression was scored according to standardized criteria originally developed for HER 2. Chromogenic in situ hybridization for IGF1R gene was performed on 35 cases using experimental Ventana probe. The tumor was interpreted as positive for gene amplification when the ration of IGF1R gene signal to chromosome 15 signal was ≥ 2.2. For statistical analysis, the IGF1R scores (0, 1, 2, 3) were dichotomized as low (0-2) vs. high (3). Association between IGF1R protein expression and clinicopathologic variables (lymph node metastases, grade, race, age) was analyzed using Fisher's exact test. The association between tumor size and IGF1R expression was analyzed using the Wilcoxon two-sample test. The overall survival was analyzed using LogRank test and Cox proportional hazard model. Results: A significant association was observed between IGF1R protein expression and IGF1R gene amplification (p<0.001). Respectively, the agreement between IGF1R 3+ protein expression and gene amplification was high (kappa=0.84, 95% CI: 0.62, 1.0; p<0.001). Low (0-2+) IGF1R expression was associated with lymph node metastases (p=0.033) while cases with high (3+) expression had borderline significantly (p=0.080) smaller tumor size. There was no statistically significant association between IGF1R expression and grade or race. In younger patients (<55 years), high IGF1R score was associated with longer survival (HR=0.13; 95% CI: 0.02- 1.00; p=0.050), while in older patients, no significant survival differences were observed between patients with low and high IGF1R scores. Conclusion: This study suggests that IGF1R is overexpressed and amplified in a subset of TNBC and may be a potential therapeutic target.