Abstract 1792: Phospho-IGF-1R/IR provides independent prognostic information in primary breast cancer but is not associated with prognosis in endocrine-treated patients

Abstract

Abstract Introduction The insulin-like growth factor (IGF) system is implicated in several cancers including breast cancer. Phosphorylated IGF type I receptor/insulin receptor (pIGF-1R/IR) indicates active IGF signaling. The signaling network may interfere with several treatment mechanisms and be involved in endocrine resistance. However, the prognostic value of pIGF-1R/IR in breast cancer is unclear. Aim and methods In order to elucidate the significance of activated IGF-IR/IR in breast cancer, the level of receptor phosphorylation was evaluated by immunohistochemistry on invasive breast cancer tissue microarrays from 984 primary breast cancer patients included in a population-based cohort in Sweden. Patients were followed for up to 11 years, the median follow-up for patients still at risk was five years. Phospho-IGF-1R/IR in relation to prognosis was analyzed using Cox regression, adjusted for age, invasive tumor size, axillary lymph node involvement, histological grade, estrogen receptor (ER) status, and body mass index. Results Phospho-IGF-1R/IR status was available for 902 patients (91.7%). Any positive cytoplasmic or membranous staining for pIGF-1R/IR was present in 749 patients (83.0%). pIGF-1R/IR+ was associated with ER+ OR (1.76; 95% CI 1.09-2.83). During follow-up, 112 patients had a first breast cancer event. Patients with pIGF-1R/IR positive tumors had lower risk for any breast cancer event compared to patients without pIGF-1R/IR (Log Rank P = 0.016), adjusted HR (0.60; 95% CI 0.40-0.91). In patients with ER+ tumors (n = 792, 87.9%), pIGF-1R/IR was evaluated in relation to prognosis and endocrine treatment. In patients who had not received endocrine treatment, pIGF-1R/IR was associated with significantly lower risk for any breast cancer event adjusted HR (0.37; 95% CI 0.15-0.92). In contrast, pIGF-1R/IR was not associated with prognosis in endocrine-treated patients adjusted HR (0.90; 95% CI 0.50-1.63). Conclusions These results indicate that IGF-1R/IR activation status may add independent prognostic information in primary breast cancer. In contrast to previous studies, pIGF-1R/IR+ was associated with better prognosis overall in this cohort. However, pIGF-1R/IR+ was not associated with prognosis in endocrine-treated patients. Taken together, these results are in line with the negative results from clinical trials with IGF-1R inhibitors in breast cancer patients, and highlight the complexity of the IGF-system. Citation Format: Sofie Björner, Ann Rosendahl, Maria Simonsson, Andrea Markkula, Karin Jirström, Signe Borgquist, Carsten Rose, Christian Ingvar, Helena Jernström. Phospho-IGF-1R/IR provides independent prognostic information in primary breast cancer but is not associated with prognosis in endocrine-treated patients. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1792.