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Breast Cancer Research
Published in: Breast Cancer Research 1/2016

Open Access 01-12-2016 | Research article

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: Stefanie de Groot, Ayoub Charehbili, Hanneke W. M. van Laarhoven, Antien L. Mooyaart, N. Geeske Dekker-Ensink, Saskia van de Ven, Laura G. M. Janssen, Jesse J. Swen, Vincent T. H. B. M. Smit, Joan B. Heijns, Lonneke W. Kessels, Tahar van der Straaten, Stefan Böhringer, Hans Gelderblom, Jacobus J. M. van der Hoeven, Henk-Jan Guchelaar, Hanno Pijl, Judith R. Kroep, on behalf of the Dutch Breast Cancer Research Group

Published in: Breast Cancer Research | Issue 1/2016

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Abstract

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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Metadata
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
Stefanie de Groot
Ayoub Charehbili
Hanneke W. M. van Laarhoven
Antien L. Mooyaart
N. Geeske Dekker-Ensink
Saskia van de Ven
Laura G. M. Janssen
Jesse J. Swen
Vincent T. H. B. M. Smit
Joan B. Heijns
Lonneke W. Kessels
Tahar van der Straaten
Stefan Böhringer
Hans Gelderblom
Jacobus J. M. van der Hoeven
Henk-Jan Guchelaar
Hanno Pijl
Judith R. Kroep
on behalf of the Dutch Breast Cancer Research Group
Publication date
01-12-2016
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 1/2016
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/s13058-015-0663-3

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