Divergent effects of insulin-like growth factor-1 receptor expression on prognosis of estrogen receptor positive versus triple negative invasive ductal breast carcinoma

Hartog, Hermien; Horlings, Hugo M.; Vegt, Bert van der; Kreike, Bas; Ajouaou, Abderrahim; Vijver, Marc J. van de; Boezen, H. Marike; Bock, Geertruida H. de; Graaf, Winette T.A. van der; Wesseling, Jelle

doi:10.1007/s10549-010-1256-6

Cited by 54 publications

(67 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…We scored staining intensity and percentage positive tumor cells, and used the continuous expression data to validate our binary analyses. Median expression levels in our study corresponded with median expression levels and cut-offs used in previous studies examining these proteins [25][26][27][28][29]. The percentages of positive expression for p-ER, EGFR, p-ERK1/2, p-mTOR and IGF1R were also in line with previous published data, using similar population selection, IHC methods, and assessment criteria in primary invasive breast tumors [26,27,29,35,42].…”

Section: Discussionsupporting

confidence: 89%

“…Therefore, expression of these proteins should be interpreted in the context of breast cancer subtype [29]. In our study, adjustment for ER status did not materially change the results and adjustment for breast cancer subtype led to slightly stronger associations of insulin with IGF1R and p-mTOR.…”

Section: Discussionmentioning

confidence: 50%

“…P-ERK1/2 was considered positive if either nuclear or cytoplasmic staining was present in ≥10% of the cells [27]. IGF1R expression was scored negative for no staining or weak partial membrane or cytoplasmic staining and was scored positive if ≥10% of the tumor cells had a moderate or strong complete membrane or cytoplasmic staining [28,29]. Figure 2 gives an overview of protein expression patterns of all proteins that were stained with moderate to strong staining.…”

Section: Tumor Block Collection and Immunohistochemical (Ihc) Analysesmentioning

confidence: 99%

See 2 more Smart Citations

The association of diabetes mellitus and insulin treatment with expression of insulin-related proteins in breast tumors

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 50%

Section: Tumor Block Collection and Immunohistochemical (Ihc) Analysesmentioning

confidence: 99%

See 1 more Smart Citation

The association of diabetes mellitus and insulin treatment with expression of insulin-related proteins in breast tumors

et al. 2018

Self Cite

View full text Add to dashboard Cite

show abstract

“…Hartog et al have revealed divergent effects of IGF1R expression on the prognosis of ER(+) cancers versus triple negative invasive ductal breast carcinoma. IGF1R expression in ER(+) tumors is strongly related to a favorable disease-free survival and breast cancer specific survival, but to a shorter survival in triple negative carcinoma [35]. Increased IGF1R mRNA levels according to intrinsic subtypes were found in 53% of Luminal A, 24% of Luminal B, 13% of HER2 and 10% of triple negative tumors, respectively [36].…”

Section: Discussionmentioning

confidence: 99%

Apoptosis-, proliferation, immune function-, and drug resistance- related genes in ER positive, HER2 positive and triple negative breast cancer

Kołacińska

Chałubińska²,

Zawlik³

et al. 2012

neo

View full text Add to dashboard Cite

The aim of our study was to examine an association between gene expression assessed using a 23-gene microarray and receptor status of breast cancer samples categorized as ER positive, HER2 positive and triple negative subtypes. The ER positive cohort was subsequently divided into Luminal A, Luminal B HER2 negative and Luminal B HER2 positive subtypes. Core-needle biopsies were collected from 78 female patients with inoperable locally advanced breast cancer or resectable tumors suitable for downstaging, before any treatment. Expressions of 23 genes were determined by means of TagMan Low Density Arrays. Analysis of variance was used to select genes with discriminatory potential between receptor subtypes. We introduced a correction for false discovery rates (presented as q values) due to testing multiple hypothesis. Pairwise post-hoc comparisons of receptor subtypes were performed using Tukey 's HSD test. Five genes out of a 23-gene microarray differed significantly in relation to breast cancer receptor-based subtypes. Among these five genes, we identified: BCL2 (p=0.0002, q=0.0009), MKI67 (p=0.0037, q=0.0064), IGF1R (p=0.0040, q=0.0064), FOXC1 (p=0.0113, q=0.0135) and IRF1 (p=0.0435, q=0.0416) as ones showing ER positive, HER2 positive and triple negative -subtype specific expression profiles. When incorporating Luminal A, Luminal B HER2 negative, Luminal B HER2 positive subtypes into analysis, four genes: BCL2 (p=0.0006, q=0.0034), MKI67 (p=0.0078, q=0.0198), FOXC1 (p=0.0102, q=0.0198) and IGF1R (p=0.0174, q=0.0254) were selected. Elevated levels of IGF1R and BCL2 were significantly linked with Luminal A subtype. Triple negative breast cancer subtype was associated with higher expression of IRF1, FOXC1 and MKI67. In HER2 positive cohort lower expression of all five analyzed genes was noted.

show abstract

“…Although high tumor IGF1R expression is reported to be a poor prognostic indicator in a variety of cancers including gastric (Matsubara et al 2008), colorectal (Takahari et al 2009), renal cell carcinoma (Sichani et al 2010), and in some breast cancer subtypes (Taunk et al 2010, Hartog et al 2011, few proposed markers to predict responsiveness to IGF1R-targeting therapies have progressed beyond preliminary reports. Cell-line studies in sarcoma and neuroblastoma show that sensitivity toward TKI BMS-536924 was associated with high IGF-1, IGF-2 and IGF1R expression, with drug resistance associated with the expression of IGFBP-3 and IGFBP-6 (Huang et al 2009).…”

Section: Predictive Biomarkers Of Igf1r Therapy Responsementioning

confidence: 99%

Combination therapy approaches to target insulin-like growth factor receptor signaling in breast cancer

Ochnik

Baxter

2016

Endocrine-Related Cancer

View full text Add to dashboard Cite

Insulin-like growth factor receptor (IGF1R) signaling as a therapeutic target has been widely studied and clinically tested. Despite the vast amount of literature supporting the biological role of IGF1R in breast cancer, effective clinical translation in targeting its activity as a cancer therapy has not been successful. The intrinsic complexity of cancer cell signaling mediated by many tyrosine kinase growth factor receptors that work together to modulate each other and intracellular downstream mediators in the cell highlights that studying IGF1R expression and activity as a prognostic factor and therapeutic target in isolation is certainly associated with problems. This review discusses the current literature and clinical trials associated with IGF-1 signaling and attempts to look at new ways of designing novel IGF1R-directed breast cancer therapy approaches to target its activity and/or intracellular downstream signaling pathways in IGF1R-expressing breast cancers. 23:11 Review A M Ochnik and R C BaxterDual IGF-directed breast cancer therapies

show abstract

Divergent effects of insulin-like growth factor-1 receptor expression on prognosis of estrogen receptor positive versus triple negative invasive ductal breast carcinoma

Cited by 54 publications

References 52 publications

The association of diabetes mellitus and insulin treatment with expression of insulin-related proteins in breast tumors

The association of diabetes mellitus and insulin treatment with expression of insulin-related proteins in breast tumors

Apoptosis-, proliferation, immune function-, and drug resistance- related genes in ER positive, HER2 positive and triple negative breast cancer

Combination therapy approaches to target insulin-like growth factor receptor signaling in breast cancer

Contact Info

Product

Resources

About