Abstract
BackgroundThe insulin-like growth factor 1 (IGF-1) pathway is involved in cell growth and proliferation and is associated with tumorigenesis and therapy resistance. This study aims to elucidate whether variation in the IGF-1 pathway is predictive for pathologic response in early HER2 negative breast cancer (BC) patients, taking part in the phase III NEOZOTAC trial, randomizing between 6 cycles of neoadjuvant TAC chemotherapy with or without zoledronic acid.MethodsFormalin-fixed paraffin-embedded tissue samples of pre-chemotherapy biopsies and operation specimens were collected for analysis of IGF-1 receptor (IGF-1R) expression (n = 216) and for analysis of 8 candidate single nucleotide polymorphisms (SNPs) in genes of the IGF-1 pathway (n = 184) using OpenArray® RealTime PCR. Associations with patient and tumor characteristics and chemotherapy response according to Miller and Payne pathologic response were performed using chi-square and regression analysis.ResultsDuring chemotherapy, a significant number of tumors (47.2 %) showed a decrease in IGF-1R expression, while in a small number of tumors an upregulation was seen (15.1 %). IGF-1R expression before treatment was not associated with pathological response, however, absence of IGF-1R expression after treatment was associated with a better response in multivariate analysis (P = 0.006) and patients with a decrease in expression during treatment showed a better response to chemotherapy as well (P = 0.020). Moreover, the variant T allele of 3129G > T in IGF1R (rs2016347) was associated with a better pathological response in multivariate analysis (P = 0.032).ConclusionsAbsent or diminished expression of IGF-1R after neoadjuvant chemotherapy was associated with a better pathological response. Additionally, we found a SNP (rs2016347) in IGF1R as a potential predictive marker for chemotherapy efficacy in BC patients treated with TAC.Trial registrationClinicalTrials.gov NCT01099436. Registered April 6, 2010.
Highlights
The insulin-like growth factor 1 (IGF-1) pathway is involved in cell growth and proliferation and is associated with tumorigenesis and therapy resistance
Absent or diminished expression of Insulin-like growth factor (IGF)-1R after neoadjuvant chemotherapy was associated with a better pathological response
We found a Single nucleotide polymorphism (SNP) in IGF1R as a potential predictive marker for chemotherapy efficacy in breast cancer (BC) patients treated with TAC
Summary
The insulin-like growth factor 1 (IGF-1) pathway is involved in cell growth and proliferation and is associated with tumorigenesis and therapy resistance. Insulin-like growth factor (IGF)-1 and other members of the IGF-1 pathway have been associated with development, progression, and metastasis of several cancers [1, 2]. The biological activity of IGF-1 and IGF-2 depends on binding with the insulin-like growth factor binding proteins (IGF-BPs), mainly IGFBP3 [12, 13]. Both IGFs bind the IGF-1R and activate the Ras/mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3-kinase (PI3K)/AKT pathways, through which cell proliferation is stimulated and apoptosis is inhibited, respectively [14, 15]. The IGF-1R and the estrogen receptor (ER) have been shown to work synergistically, whereby activated ER binds to the promoter regions of IGF1R to promote transcription and IGF-1 is able to activate unliganded ER [16, 17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
