IGF1R and phosphorylated IGF1R in HER2-positive breast cancer.

Abstract

587 Background: IGF receptor (IGF1R) signalling has been implicated in resistance to trastuzumab in HER2 positive breast cancer in vitro. However, two previous studies on HER2 positive breast tumors showed that IGF1R expression does not correlated with response to trastuzumab. The relationship between activation of the IGF1R and response to trastuzumab has not been examined in HER2 positive tumours. The aims of this study were to examine IGFIR and phosphorylated IGFIR (pIGF1R) in HER2 positive breast tumours, and to correlate IGFIR and pIGFIR with response to trastuzumab. Methods: Formalin-fixed paraffin-embedded tumour samples were obtained from 160 HER-2 positive breast cancer patients. Tissue microarrays were constructed using 4 cores from each specimen. Antigen retrieval was performed using pH6 antigen retrieval buffer (DAKO) and immunohistochemical (IHC) staining was performed on an autostainer (DAKO) using an IGF1R antibody and an antibody which detects phosphorylated IGF1R or insulin receptor (pIGF1R/IR). IHC results were correlated with tumor characteristics using Chi Square tests. Survival data was available for 94 HER2 positive early stage breast cancer patients who received trastuzumab, (median follow up 5.1 yrs). Survival analysis was performed using Kaplan Meier curves. Results: Membrane staining for IGF1R (mIGF1R) was detected in only 13.8 % of tumors (22/16), while varying degrees of cytoplasmic IGF1R (cIGF1R) staining were detected in all samples. mIGF1R was detected more frequently in larger tumors (>2 cm) (p=0.0414) and was detected in Grade 2 and 3 tumors but not in Grade 1 tumors (p=0.0239). pIGF1R/IR was detected in 48.8 % of tumors tested (78/160). pIGF1/IR was detected more frequently in node negative (57.6%) than node positive tumors (41.9%) although this difference did not achieve statistical significance (p=0.0592). In the trastuzumab treated cohort of HER2 positive early stage breast cancer patients (n=94), mIGF1R, cIGF1R and pIGF1R/IR did not correlate with patient survival (mIGF1R: p = 0.319; cIGF1R: p = 0.686; pIGF1R/IR: p = 0.504). Conclusions: Phosphorylated IGF1R/IR is detected in 49% of HER2 positive breast tumors but does not seem to predict response or resistance to trastuzumab in early stage breast cancer.