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

Björner, Sofie LU ; Rosendahl, Ann H. LU ; Simonsson, Maria LU ; Markkula, Andrea LU ; Jirström, Karin LU ; Borgquist, Signe LU ; Rose, Carsten LU ; Ingvar, Christian LU and Jernström, Helena LU (2017) In Oncotarget 8(6). p.9093-9107
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 populationbased 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... (More)

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 populationbased 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 endocrinetreated 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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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Breast cancer, Insulin receptor, Insulin-like growth factor-I receptor, Phospho-insulin-like growth factor-I receptor/insulin receptor, Prognosis
in
Oncotarget
volume
8
issue
6
pages
15 pages
publisher
Impact Journals, LLC
external identifiers
  • scopus:85011995620
  • wos:000394181800019
ISSN
1949-2553
DOI
10.18632/oncotarget.14082
language
English
LU publication?
yes
id
5b0f94a1-71f4-494a-9f53-c5da14f10c72
date added to LUP
2017-03-03 12:14:39
date last changed
2018-01-07 11:53:52
@article{5b0f94a1-71f4-494a-9f53-c5da14f10c72,
  abstract     = {<p>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 populationbased 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. IGF1R<sup>strong</sup>/InsR<sup>mod/strong</sup>/pIGF1R/InsR<sup>pos</sup> tumors were borderline associated with 2-fold risk for events, HR<sub>adj</sub> (2.00; 95%CI 0.96-4.18). Combined IGF1R and pIGF1R/InsR status only impacted prognosis in patients with InsR<sup>mod/strong</sup> expressing tumors (P<sub>interaction</sub> = 0.041). IGF1R<sup>strong</sup> expression impacted endocrine treatment response differently depending on patients' age and type of endocrine therapy. Phospho-IGF1R/InsR<sup>pos</sup> was associated with lower risk for events among non-endocrine-treated patients irrespective of ER status, HR<sub>adj</sub> (0.32; 95%CI 0.16-0.63), but not among endocrinetreated patients (P<sub>interaction</sub> = 0.024). In non-endocrine-treated patients, pIGF1R/InsR<sup>pos</sup> was associated with lower risk for events after radiotherapy, HR<sub>adj</sub> (0.31; 95%CI 0.12-0.80), and chemotherapy, HR<sub>adj</sub> (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.</p>},
  author       = {Björner, Sofie and Rosendahl, Ann H. and Simonsson, Maria and Markkula, Andrea and Jirström, Karin and Borgquist, Signe and Rose, Carsten and Ingvar, Christian and Jernström, Helena},
  issn         = {1949-2553},
  keyword      = {Breast cancer,Insulin receptor,Insulin-like growth factor-I receptor,Phospho-insulin-like growth factor-I receptor/insulin receptor,Prognosis},
  language     = {eng},
  number       = {6},
  pages        = {9093--9107},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {Combined and individual tumor-specific expression of insulinlike growth factor-I receptor, insulin receptor and phosphoinsulin- like growth factor-I receptor/insulin receptor in primary breast cancer : Implications for prognosis in different treatment groups},
  url          = {http://dx.doi.org/10.18632/oncotarget.14082},
  volume       = {8},
  year         = {2017},
}