Combined and individual tumor-specific expression of insulin-like growth factor-I receptor, insulin receptor and phospho-insulin-like growth factor-I receptor/insulin receptor in primary breast cancer: Implications for prognosis in different treatment groups.

Abstract

Clinical trials examining insulin-like growth factor-I receptor (IGF1R)-targeting strategies have emphasized that better predictive biomarkers are required to improve patient selection.Immunohistochemical tumor-specific protein expression of IGF1R, insulin receptor (InsR), and phosphorylated IGF1R/InsR (pIGF1R/InsR) individually and combined in relation to breast cancer prognosis was evaluated in a population-based cohort of 1,026 primary invasive breast cancer patients without preoperative treatment diagnosed in Sweden. IGF1R (n = 923), InsR (n = 900), and pIGF1R/InsR (n = 904) combined cytoplasmic and membrane staining was dichotomized. IGF1Rstrong/InsRmod/strong/pIGF1R/InsRpos tumors were borderline associated with 2-fold risk for events, HRadj (2.00; 95%CI 0.96-4.18). Combined IGF1R and pIGF1R/InsR status only impacted prognosis in patients with InsRmod/strong expressing tumors (Pinteraction = 0.041). IGF1Rstrong expression impacted endocrine treatment response differently depending on patients' age and type of endocrine therapy. Phospho-IGF1R/InsRpos was associated with lower risk for events among non-endocrine-treated patients irrespective of ER status, HRadj (0.32; 95%CI 0.16-0.63), but not among endocrine-treated patients (Pinteraction = 0.024). In non-endocrine-treated patients, pIGF1R/InsRpos was associated with lower risk for events after radiotherapy, HRadj (0.31; 95%CI 0.12-0.80), and chemotherapy, HRadj (0.29; 95%CI 0.09-0.99). This study highlights the complexity of IGF hetero-and homodimer signaling network and its interplay with endocrine treatment, suggesting that combinations of involved factors may improve patient selection for IGF1R-targeted therapy.

• Authors: Sofie Björner, Ann H Rosendahl, Maria Simonsson, Andrea Markkula, Karin Jirström, Signe Borgquist, Carsten Rose, Christian Ingvar, Helena Jernström
• Journal: Oncotarget (Oncotarget) Vol. 8 Issue 6 Pg. 9093-9107 (Feb 07 2017) ISSN: 1949-2553 [Electronic] United States
• PMID: 28030849 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antigens, CD
• Antineoplastic Agents, Hormonal
• Biomarkers, Tumor
• IGF1R protein, human
• Receptors, Estrogen
• Receptors, Somatomedin
• INSR protein, human
• Receptor, IGF Type 1
• Receptor, Insulin

Topics

• Antigens, CD (analysis)
• Antineoplastic Agents, Hormonal (therapeutic use)
• Biomarkers, Tumor (analysis)
• Breast Neoplasms (chemistry, mortality, pathology, therapy)
• Disease-Free Survival
• Female
• Humans
• Immunohistochemistry
• Kaplan-Meier Estimate
• Neoplasm Invasiveness
• Phosphorylation
• Predictive Value of Tests
• Proportional Hazards Models
• Radiotherapy
• Receptor, IGF Type 1
• Receptor, Insulin (analysis)
• Receptors, Estrogen (analysis)
• Receptors, Somatomedin (analysis, antagonists & inhibitors)
• Sweden
• Time Factors
• Treatment Outcome