TY - JOUR
T1 - Insulin-like growth factor receptor (IGF-1R) in breast cancer subtypes
AU - Yerushalmi, Rinat
AU - Gelmon, Karen A.
AU - Leung, Samuel
AU - Gao, Dongxia
AU - Cheang, Maggie
AU - Pollak, Michael
AU - Turashvili, Gulisa
AU - Gilks, Blakes C.
AU - Kennecke, Hagen
N1 - Funding Information:
Acknowledgments Thanks to Prof. Torsten Nielsen’s (MD/PHD) helpful comments. GPEC lab is supported through unrestricted educational funds from Sanofi Aventis Canada.
PY - 2012/2
Y1 - 2012/2
N2 - 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.
AB - 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.
KW - Basal-like, HER2
KW - IGF-1R, breast cancer
KW - Insulin-like growth factor receptor
KW - Subtypes
UR - http://www.scopus.com/inward/record.url?scp=84857920393&partnerID=8YFLogxK
U2 - 10.1007/s10549-011-1529-8
DO - 10.1007/s10549-011-1529-8
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C2 - 21574055
AN - SCOPUS:84857920393
SN - 0167-6806
VL - 132
SP - 131
EP - 142
JO - Breast Cancer Research and Treatment
JF - Breast Cancer Research and Treatment
IS - 1
ER -