Author(s):
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Groot, S. de; Charehbili, A.;
Laarhoven, H.W.M. van
; Mooyaart, A.L.; Dekker-Ensink, N.G.; Ven, S. van de; Janssen, L.G.; Swen, J.J.; Smit, V.T.; Heijns, J.B.; Kessels, L.W.; Straaten, T. van der; Bohringer, S.; Gelderblom, H.;
Hoeven, J.J. van der
; Guchelaar (LUMC), H.J.; Pijl, H.; Kroep, J.R.
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Subject:
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Radboudumc 17: Women's cancers RIHS: Radboud Institute for Health Sciences Radboudumc 2: Cancer development and immune defence RIHS: Radboud Institute for Health Sciences |
Organization:
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Medical Oncology Radboudumc Extern |
Abstract:
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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(R) 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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