title: Insulin-like growth factor receptor (IGF-1R) in breast cancer subtypes.
abstract: Insulin-like growth factor-1 receptor (IGF-1R) is expressed in normal and malignant breast tissue and has been implicated in cell survival and resistance to cytotoxic therapies. We sought to assess the prognostic impact of IGF-1R expression among patients with early breast cancer and among breast cancer subtypes. Patients with stages I-III breast cancer with archival tumor tissue were included. Paraffin tissue blocks were used to construct a tissue microarray that was stained for ER, PR, Ki-67, HER2, EGFR, and cytokeratins 5/6 to classify the breast subgroups and for expression of IGF-1R, p27, and Bcl2 by immunohistochemistry. Kaplan-Meier plots were created by subtypes. Associations between IGF-1R and prognostic variables were examined in multivariate analysis. Among 2,871 eligible women the prognostic cut point for IGF-1R expression for breast-cancer-specific survival (BCSS) was Allred score < 7 versus ≥ 7. IGF-1R was ≥ 7 in 52% (LuminalA), 57.5% (LuminalB), 44.8% (LuminalHER2), 9.7% HER2-enriched, and 22.5% (Basal-like), P = 1.3 × 10(-52). IGF-1R+ was associated with age ≥ 50, lower histopathology grade, ER+, HER2 negativity (-), high p27 and high Bcl2 score. IGF-1R ≥ 7 was associated with better BCSS among LuminalB patients, hazard ratio = 0.64 (0.49-0.84); P = 1.2 × 10(-3,) and worse outcome in the HER2-enriched subtype, hazard ratio = 2.37 (1.21-4.64); P = 0.012. IGF-1R correlates with good prognostic markers among patients with early breast cancer and is differentially expressed with variable prognostic impact among breast cancer subtypes. Results may have relevance to the development of therapeutics targeting IGF-1R.
authors.affiliation: Division of Medical Oncology, BC Cancer Agency, Cancer Agency, 600 W 10th Avenue, Vancouver, BC V5Z 4E6, Canada.
authors.forename: Rinat
authors.initials: R
authors.lastname: Yerushalmi
authors.forename: Karen A
authors.initials: KA
authors.lastname: Gelmon
authors.forename: Samuel
authors.initials: S
authors.lastname: Leung
authors.forename: Dongxia
authors.initials: D
authors.lastname: Gao
authors.forename: Maggie
authors.initials: M
authors.lastname: Cheang
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
authors.forename: Gulisa
authors.initials: G
authors.lastname: Turashvili
authors.forename: Blakes C
authors.initials: BC
authors.lastname: Gilks
authors.forename: Hagen
authors.initials: H
authors.lastname: Kennecke
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D016022:Case-Control Studies; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D011379:Prognosis; D016016:Proportional Hazards Models; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D047368:Tumor Burden
chemical_list: D014408:Biomarkers, Tumor; D019253:Proto-Oncogene Proteins c-bcl-2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D017526:Receptor, IGF Type 1