Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Winder, T; Giamas, G; Wilson, PM; Zhang, W; Yang, D; Bohanes, P; Ning, Y; Gerger, A; Stebbing, J; Lenz, HJ.
Insulin-like growth factor receptor polymorphism defines clinical outcome in estrogen receptor-positive breast cancer patients treated with tamoxifen.
Pharmacogenomics J. 2014; 14(1):28-34
Doi: 10.1038/tpj.2013.8
Web of Science
PubMed
FullText
FullText_MUG
- Co-authors Med Uni Graz
- Gerger Armin
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Compelling evidence points to a key role for insulin-like growth factor 1 (IGF1) signaling in breast cancer development and progression. In addition, IGF1 receptor (IGF1R) expression has been correlated and functionally linked with estrogen receptor (ER) signaling. Recent translational studies support a cross talk between IGF1R and ERα at different levels and data suggest enhanced IGF1R signaling as a causative mechanism of tamoxifen (TAM) resistance. We tested whether functional germline variations in the IGF pathway are associated with clinical outcome in ER-positive primary invasive breast cancer patients, who were treated with surgery and adjuvant TAM. Tissue samples of 222 patients with ER+ primary invasive breast cancer, who had undergone surgery at Charing Cross Hospital, London, UK between 1981 and 2003, were analyzed. Genomic DNA was extracted from formalin-fixed, paraffin-embedded tissue samples and six functional IGF1 pathway polymorphisms were analyzed using direct DNA sequencing and PCR-restriction fragment length polymorphism. In multivariable analysis, patients with primary invasive breast cancer carrying IGF1R_rs2016347 G allele had a significantly increased risk of early tumor progression (hazard ratio (HR) 2.01; adjusted P=0.004) and death (HR 1.84; adjusted P=0.023) compared with patients carrying G/T or T/T, independent of established clinicopathological determinants. This association remained significant after adjusting for multiple testing. In addition, we were able to demonstrate that IRS1_rs1801123 and IGFBP3_rs2854744 were significantly associated with lymph node involvement and tumor size, respectively. We provide the first evidence for IGF1R_rs2016347 as an independent prognostic marker for ER+ breast cancer patients treated with TAM and support a rational for combined treatment strategies.
- Find related publications in this database (using NLM MeSH Indexing)
- Amplified Fragment Length Polymorphism Analysis -
- Breast Neoplasms - drug therapy
- Breast Neoplasms - genetics
- Breast Neoplasms - pathology
- Breast Neoplasms - surgery
- Chemotherapy, Adjuvant -
- Combined Modality Therapy -
- Disease-Free Survival -
- Female -
- Humans -
- Multivariate Analysis -
- Neoplasm Invasiveness -
- Polymorphism, Single Nucleotide -
- Receptor, IGF Type 1 - genetics
- Receptors, Estrogen - antagonists & inhibitors
- Receptors, Estrogen - metabolism
- Selective Estrogen Receptor Modulators - administration & dosage
- Selective Estrogen Receptor Modulators - therapeutic use
- Tamoxifen - administration & dosage
- Tamoxifen - therapeutic use
- Find related publications in this database (Keywords)
- IGF1R
- breast cancer
- outcome
- polymorphisms