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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)
- Source :
- Breast Cancer Research, 18, 3, Breast Cancer Research, 18, 1, pp. 3, Breast Cancer Research : BCR, Breast Cancer Research, 18, Breast cancer research, 18(1). BioMed Central
- Publication Year :
- 2016
-
Abstract
- Contains fulltext : 165680.pdf (Publisher’s version ) (Open Access) 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.
- Subjects :
- 0301 basic medicine
Oncology
Pathology
medicine.medical_treatment
Receptor expression
IGF-BP3
Receptor, IGF Type 1
Insulin-like growth factor
Cancer development and immune defence Radboud Institute for Health Sciences [Radboudumc 2]
0302 clinical medicine
Breast cancer
Surgical oncology
Antineoplastic Combined Chemotherapy Protocols
Insulin
Neoadjuvant therapy
Medicine(all)
Predictive marker
Middle Aged
Prognosis
Neoadjuvant Therapy
Women's cancers Radboud Institute for Health Sciences [Radboudumc 17]
Gene Expression Regulation, Neoplastic
030220 oncology & carcinogenesis
IGF-1
Female
Research Article
Adult
medicine.medical_specialty
Breast Neoplasms
Polymorphism, Single Nucleotide
Neoadjuvant chemotherapy
03 medical and health sciences
Internal medicine
medicine
Biomarkers, Tumor
Humans
Genetic Association Studies
Insulin-like growth factor 1 receptor
Aged
Chemotherapy
Pathological complete response
business.industry
Receptors, Somatomedin
Single nucleotide polymorphisms
medicine.disease
030104 developmental biology
Glucose
business
IGF-1R
Miller and Payne
Subjects
Details
- ISSN :
- 14655411
- Database :
- OpenAIRE
- Journal :
- Breast Cancer Research, 18, 3, Breast Cancer Research, 18, 1, pp. 3, Breast Cancer Research : BCR, Breast Cancer Research, 18, Breast cancer research, 18(1). BioMed Central
- Accession number :
- edsair.doi.dedup.....b3eafc4f912277b720127dc80c392b0d