| Autor: |
Björner S; Department of Clinical Sciences Lund, Lund University Faculty of Medicine, Oncology and Pathology, Lund, Sweden., Rosendahl AH; Department of Clinical Sciences Lund, Lund University Faculty of Medicine, Oncology and Pathology, Lund, Sweden., Simonsson M; Department of Clinical Sciences Lund, Lund University Faculty of Medicine, Oncology and Pathology, Lund, Sweden., Markkula A; Department of Clinical Sciences Lund, Lund University Faculty of Medicine, Oncology and Pathology, Lund, Sweden., Jirström K; Department of Clinical Sciences Lund, Lund University Faculty of Medicine, Oncology and Pathology, Lund, Sweden., Borgquist S; Department of Clinical Sciences Lund, Lund University Faculty of Medicine, Oncology and Pathology, Lund, Sweden.; Department of Oncology and Haematology, Skåne University Hospital, Sweden., Rose C; CREATE Health and Department of Immunotechnology, Lund University, Medicon Village, Lund, Sweden., Ingvar C; Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Surgery, Lund, Sweden., Jernström H; Department of Clinical Sciences Lund, Lund University Faculty of Medicine, Oncology and Pathology, Lund, Sweden. |
| Abstrakt: |
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. |
