Gene Pathways Associated With Prognosis and Chemotherapy Sensitivity in Molecular Subtypes of Breast Cancer

Inomata, Takayuki; Bianchini, Giampaolo; Booser, Daniel J.; Qi, Yuan; Coutant, Charles; Shiang, Christine Y.; Santarpia, Libero; Matsuoka, Junji; Hortobágyi, Gabriel N.; Symmans, W. Fraser; Holmes, Frankie A.; O’Shaughnessy, Joyce; Hellerstedt, Beth A.; Pippen, John; Varga, Andrea; Simon, Richard; Pusztai, Lajos

doi:10.1093/jnci/djq524

Cited by 210 publications

(182 citation statements)

References 31 publications

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“…In our hands, when used at a final concentration of 5 µM, neither drug was able to block persistent EGFR tyrosine phosphorylation in lapatinib resistant cells-maintained in 1 µM lapatinib-nor did they restore lapatinib sensitivity ( Figure 6A and B). Neratinib, in contrast to lapatinib, gefitinib and erlotinib is an irreversible EGFR and HER2 TKI [43]. Consistent with previous reports [43], we found that neratinib was a potent inhibitor of parental HER2+ breast cancer cells (Additional file 7).…”

Section: Egfr Represents An Attractive Target In Lapatinib Resistant supporting

confidence: 89%

“…Neratinib, in contrast to lapatinib, gefitinib and erlotinib is an irreversible EGFR and HER2 TKI [43]. Consistent with previous reports [43], we found that neratinib was a potent inhibitor of parental HER2+ breast cancer cells (Additional file 7). Neratinib, when used at higher concentrations than in parental cell cultures, inhibited persistent phosphorylation of EGFR, HER3 and Akt T308 in resistant cells, triggering cell apoptosis (increased cleaved PARP), and inhibition of cell growth and viability (P < 0.0008 in rSKBR3; P < 0.0025 in rBT474) ( Figure 6A and B).…”

Section: Egfr Represents An Attractive Target In Lapatinib Resistant supporting

confidence: 89%

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Rapid Translation of a Novel and Potent Vaccine in HER2+ Metastatic Breast Cancer Patients

Lyerly¹

2013

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Section: Egfr Represents An Attractive Target In Lapatinib Resistant supporting

confidence: 89%

Section: Egfr Represents An Attractive Target In Lapatinib Resistant supporting

confidence: 89%

Rapid Translation of a Novel and Potent Vaccine in HER2+ Metastatic Breast Cancer Patients

Lyerly¹

2013

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“…pCR was defined as loss of the invasive component of the primary tumor in one study (33) and no residual invasive cancer in the breast and axillary lymph nodes in other seven studies (34)(35)(36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

“…We further evaluated whether AR mRNA expression were associated with response to neoadjuvant CT (anthracyclines AE taxanes). Out of 1,005 patients from eight datasets (33)(34)(35)(36)(37)(38), 235 (23%) patients achieved pCR, 765 (76%) did not, while five samples were inadequate for the analysis. High AR expression levels showed significant association with lower pCR rate (OR, 0.57; 95% CI, 0.44-0.74, P < 0.001) in the univariate analysis while not significant in a multivariate model (OR, 0.74; 95% CI, 0.54-1.01, P ¼ 0.063; Fig.…”

Section: Prognostic Significance Of Ar Expressionmentioning

confidence: 99%

The Prognostic Role of Androgen Receptor in Patients with Early-Stage Breast Cancer: A Meta-analysis of Clinical and Gene Expression Data

Božović-Spasojević

Zardavas

Brohée

et al. 2017

Clinical Cancer Research

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Purpose: Androgen receptor (AR) expression has been observed in about 70% of patients with breast cancer, but its prognostic role remains uncertain.Experimental Design: To assess the prognostic role of AR expression in early-stage breast cancer, we performed a metaanalysis of studies that evaluated the impact of AR at the protein and gene expression level on disease-free survival (DFS) and/or overall survival (OS). Eligible studies were identified by systematic review of electronic databases using the MeSH-terms "breast neoplasm" and "androgen receptor" and were selected after a qualitative assessment based on the REMARK criteria. A pooled gene expression analysis of 35 publicly available microarray data sets was also performed from patients with early-stage breast cancer with available gene expression and clinical outcome data.Results: Twenty-two of 33 eligible studies for the clinical meta-analysis, including 10,004 patients, were considered as evaluable for the current study after the qualitative assessment. AR positivity defined by IHC was associated with improved DFS in all patients with breast cancer [multivariate (M) analysis, HR 0.46; 95% confidence interval (CI) 0.37-0.58, P < 0.001] and better OS [M-HR 0.53; 95% CI, 0.38-0.73, P < 0.001]. Thirty-five datasets including 7,220 patients were eligible for the pooled gene expression analysis. High AR mRNA levels were found to confer positive prognosis overall in terms of DFS (HR 0.82; 95% CI 0.72-0.92;P ¼ 0.0007) and OS (HR 0.84; 95% CI, 0.75-0.94; P ¼ 0.02) only in univariate analysis.Conclusions: Our analysis, conducted among more than 17,000 women with early-stage breast cancer included in clinical and gene expression analysis, demonstrates that AR positivity is associated with favorable clinical outcome. Clin Cancer Res; 23(11); 2702-12. Ó2016 AACR.

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“…The more proliferative tumours are associated with a beneficial response towards the chemotherapy [54].…”

Section: Chemotherapymentioning

confidence: 99%

The receptor tyrosine kinase Met and the protein tyrosinephosphatase PTPN2 in breast cancer

Veenstra¹

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This thesis aimed to explore possible prognostic and predictive biomarkers in different subtypes and study their role in breast cancer. To this aid, breast cancer tumours of pre-and post-menopausal patients enrolled in two cohorts were analysed for gene copy numbers and expression of proteins involved in cell proliferation. Gene copy numbers of receptor tyrosine kinases MET and EGFR, Met's ligand HGF, and protein tyrosine phosphatase PTPN2 were determined by droplet digital PCR or quantitative PCR in both cohorts. Met, phosphorylated Met (pMet), HGF, and PTPN2 protein expression levels were analysed with immunohistochemical staining in the pre-menopausal cohort. Moreover, the role of the aforementioned proteins was investigated in breast cancer cell lines.Amplification of MET, HGF, and EGFR in breast tissues was found to be low (5-8%). These three genes, all located on chromosome 7, were found to be strongly correlated with each other and to be associated with shortened distant recurrence-free survival. High protein expression of Met, pMet, and HGF was found in 33%, 53%, and 49% of the breast tumours. MET and EGFR were found to be more often amplified in TNBC disease, correlating with worse survival.Moreover, stromal expression of HGF was associated with shorter survival in TNBC. EGF stimulation in TNBC cell line MDA-MB-468 led to inhibited cell

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Gene Pathways Associated With Prognosis and Chemotherapy Sensitivity in Molecular Subtypes of Breast Cancer

Abstract: Different biological processes were associated with prognosis and chemotherapy response in ER-positive and ER-negative breast cancers.

Cited by 210 publications

References 31 publications

Rapid Translation of a Novel and Potent Vaccine in HER2+ Metastatic Breast Cancer Patients

Rapid Translation of a Novel and Potent Vaccine in HER2+ Metastatic Breast Cancer Patients

The Prognostic Role of Androgen Receptor in Patients with Early-Stage Breast Cancer: A Meta-analysis of Clinical and Gene Expression Data

The receptor tyrosine kinase Met and the protein tyrosinephosphatase PTPN2 in breast cancer

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