10563 Background: The role of the insulin-like growth factor-1 receptor (IGF-1R) in the outcome of breast cancer is poorly understood. Therefore, we analyzed the prognostic value of IGF-1R expression in relation to clinically relevant tumor characteristics. Methods: Expression of IGF-1R, insulin receptor, estrogen receptor (ER), progesterone receptor (PR), HER2 receptor, epidermal growth factor receptor and phosphorylated Akt (pAkt) was determined on tissue microarrays comprising primary invasive ductal breast carcinoma samples of a consecutive series of 221 patients. Patients presented at the University Medical Center Groningen between 1996 and 2001. Patient records were reviewed for clinical and tumor parameters. Cytoplasmic and membranous IGF-1R staining were scored separately, as the relevance of IGF-1R cellular localization is yet unknown. Associations were tested by Chi-square, Log Rank test and Cox regression analysis. Results: Overall, IGF-1R expression was present in 79% of the tumors. Cytoplasmic staining was present in 69%, membranous in 52%, staining was combined cytoplasmic and membranous in 42% of the tumors. Cytoplasmic, but not membranous, IGF-1R staining was associated with expression of ER (p<0.001), PR (p=0.001), pAkt (p=0.04), and increased relapse free and overall survival (RFS, p=0.01; OS, p=0.006). No correlations with other parameters were found. In ER/PR positive, HER2 negative tumors, but not in HER2 positive tumors, cytoplasmic IGF-1R expression correlated with increased RFS (p=0.002) and OS (p=0.001). In contrast, in triple negative tumors cytoplasmic and membranous expression of IGF-1R were both significantly associated with shorter RFS (p=0.02, p=0.04, resp.). In multivariate analysis, cytoplasmic IGF-1R expression was an independent prognostic factor for OS (HR 0.3, 95% CI 0.1–0.9, p=0.035). Conclusions: Cytoplasmic IGF-1R expression in invasive ductal breast carcinoma is associated with hormone receptor expression, phosphorylated Akt and good prognosis. Surprisingly, triple negative tumors expressing IGF-1R have a worse prognosis than those without. These results suggest that IGF-1R targeted therapy may have additional value in the treatment of triple negative tumors. No significant financial relationships to disclose.
E-cadherin expression in triple-negative invasive ductal breast carcinoma
