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- Title
Insulin-like growth factor 1 receptor expression and IGF1R 3129G > T polymorphism are associated with response to neoadjuvant chemotherapy in breast cancer patients: results from the NEOZOTAC trial (BOOG 2010-01).
- Authors
de Groot, Stefanie; Charehbili, Ayoub; van Laarhoven, Hanneke W. M.; Mooyaart, Antien L.; Dekker-Ensink, N. Geeske; van de Ven, Saskia; Janssen, Laura G. M.; Swen, Jesse J.; Smit, Vincent T. H. B. M.; Heijns, Joan B.; Kessels, Lonneke W.; van der Straaten, Tahar; Böhringer, Stefan; Gelderblom, Hans; van der Hoeven, Jacobus J. M.; Guchelaar, Henk-Jan; Pijl, Hanno; Kroep, Judith R.; Dutch Breast Cancer Research Group
- Abstract
<bold>Background: </bold>The 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.<bold>Methods: </bold>Formalin-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.<bold>Results: </bold>During 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).<bold>Conclusions: </bold>Absent 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.<bold>Trial Registration: </bold>ClinicalTrials.gov NCT01099436 . Registered April 6, 2010.
- Subjects
SOMATOMEDIN C; BREAST cancer patients; CANCER chemotherapy; SINGLE nucleotide polymorphisms; INSULIN-like growth factor receptors; CELLULAR signal transduction; GENE expression; ANTINEOPLASTIC agents; BREAST tumors; CELL receptors; CLINICAL trials; COMBINED modality therapy; COMPARATIVE studies; GENES; GENETIC polymorphisms; GENETIC techniques; RESEARCH methodology; MEDICAL cooperation; PROGNOSIS; RESEARCH; EVALUATION research
- Publication
Breast Cancer Research, 2016, Vol 18, p3
- ISSN
1465-5411
- Publication type
journal article
- DOI
10.1186/s13058-015-0663-3