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
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Sofie Björner1,*, Ann H. Rosendahl1,*, Maria Simonsson1, Andrea Markkula1, Karin Jirström1, Signe Borgquist1,2, Carsten Rose3, Christian Ingvar4 and Helena Jernström1
1 Department of Clinical Sciences Lund, Lund University Faculty of Medicine, Oncology and Pathology, Lund, Sweden
2 Department of Oncology and Haematology, Skåne University Hospital, Sweden
3 CREATE Health and Department of Immunotechnology, Lund University, Medicon Village, Lund, Sweden
4 Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Surgery, Lund, Sweden
* These authors have contributed equally to this work
Helena Jernström, email:
Keywords: insulin-like growth factor-I receptor, insulin receptor, phospho-insulin-like growth factor-I receptor/insulin receptor, breast cancer, prognosis
Received: December 06, 2016 Accepted: December 15, 2016 Published: December 21, 2016
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.
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