title: 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.affiliation: Department of Clinical Sciences Lund, Lund University Faculty of Medicine, Oncology and Pathology, Lund, Sweden.
authors.forename: Sofie
authors.initials: S
authors.lastname: Björner
authors.affiliation: Department of Clinical Sciences Lund, Lund University Faculty of Medicine, Oncology and Pathology, Lund, Sweden.
authors.forename: Ann H
authors.initials: AH
authors.lastname: Rosendahl
authors.affiliation: Department of Clinical Sciences Lund, Lund University Faculty of Medicine, Oncology and Pathology, Lund, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Simonsson
authors.affiliation: Department of Clinical Sciences Lund, Lund University Faculty of Medicine, Oncology and Pathology, Lund, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Markkula
authors.affiliation: Department of Clinical Sciences Lund, Lund University Faculty of Medicine, Oncology and Pathology, Lund, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
authors.affiliation: Department of Clinical Sciences Lund, Lund University Faculty of Medicine, Oncology and Pathology, Lund, Sweden.|Department of Oncology and Haematology, Skåne University Hospital, Sweden.
authors.forename: Signe
authors.initials: S
authors.lastname: Borgquist
authors.affiliation: CREATE Health and Department of Immunotechnology, Lund University, Medicon Village, Lund, Sweden.
authors.forename: Carsten
authors.initials: C
authors.lastname: Rose
authors.affiliation: Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, Surgery, Lund, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Ingvar
authors.affiliation: Department of Clinical Sciences Lund, Lund University Faculty of Medicine, Oncology and Pathology, Lund, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Jernström
mesh_terms: D015703:Antigens, CD / Q000032:analysis*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011878:Radiotherapy; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin / Q000032:analysis*; D011960:Receptors, Estrogen / Q000032:analysis; D017451:Receptors, Somatomedin / Q000032:analysis* / Q000037:antagonists & inhibitors; D013548:Sweden; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015703:Antigens, CD; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; C000597236:IGF1R protein, human; D011960:Receptors, Estrogen; D017451:Receptors, Somatomedin; C435941:INSR protein, human; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin
keywords: breast cancer; insulin receptor; insulin-like growth factor-I receptor; phospho-insulin-like growth factor-I receptor/insulin receptor; prognosis