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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)

BACKGROUND: 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 brea...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702399/
https://www.ncbi.nlm.nih.gov/pubmed/26738606
http://dx.doi.org/10.1186/s13058-015-0663-3
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author 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.
author_facet 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.
author_sort de Groot, Stefanie
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT01099436. Registered April 6, 2010.
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spelling pubmed-47023992016-01-07 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) 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. Breast Cancer Res Research Article BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT01099436. Registered April 6, 2010. BioMed Central 2016-01-06 2016 /pmc/articles/PMC4702399/ /pubmed/26738606 http://dx.doi.org/10.1186/s13058-015-0663-3 Text en © de Groot et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
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.
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)
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)
title_full 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)
title_fullStr 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)
title_full_unstemmed 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)
title_short 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)
title_sort 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)
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4702399/
https://www.ncbi.nlm.nih.gov/pubmed/26738606
http://dx.doi.org/10.1186/s13058-015-0663-3
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