ErbB family receptor inhibitors as therapeutic agents in breast cancer: Current status and future clinical perspective

Saxena, Ruchi; Dwivedi, Anila

doi:10.1002/med.20209

Cited by 76 publications

(68 citation statements)

References 272 publications

(340 reference statements)

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“…HER2, a member of the receptor tyrosine kinase family, plays a crucial role in the growth of both normal tissue and malignant tumours (Saxena and Dwivedi, 2012). HER2 overexpression is observed in 18.9-22.4% of epithelial ovarian carcinomas (Steffensen et al, 2007), and it is reported to be seen more frequently in mucinous ovarian cancers (Yan et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Hormone Receptor, HER2/NEU and EGFR Expression in Ovarian Carcinoma - is here a Prognostic Phenotype?

Demir¹,

Yiğit²,

Sadullahoğlu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Purpose: We aimed to evaluate the effects of hormone receptor, HER2, and epidermal growth factor receptor (EGFR) expression on epithelial ovarian cancer (EOC) prognosis and investigate whether or not phenotypic subtypes might exist. Materials and Methods: The medical records of 82 patients who were diagnosed with EOC between 2003 and 2012 and treated by platinum-based chemotherapy were retrospectively evaluated. Expression of EGFR, oestrogen (ER), progesterone (PR), and cerbB2 (HER2) receptors were assessed immunohistochemically on paraffin-embedded tissues of these patients. Three phenotypic subtypes were defined according to ER, PR, and HER2 expression and associations of these with EGFR expression, clinicopathologic features, platinum sensitivity, and survival were investigated. Results: When we classified EOC patients into three subtypes, 63.4% had hormone receptor positive (HR(+)) (considering breast cancer subtypes, luminal A), 18.3% had triple negative, and 18.3% had HER2(+) disease. EGFR positivity was observed in 37 patients (45.1%) and was significantly more frequent with advanced disease (p=0.013). However, no significant association with other clinicopathologic features and platinum sensitivity was observed. HER2(+) patients had significantly poorer outcomes than HER2(-) counterparts (triple negative and HR positive patients) (p=0.019). Multivariate analysis demonstrated that the strongest risk factor for death was residual disease after primary surgery. Conclusions: Triple negative EOC may not be an aggressive phenotype as in breast cancer. The HER2 positive EOC has more aggressive behaviour compared to triple negative and HR(+) phenotypes. EGFR expression is more frequent in advanced tumours, but is not related with poorer outcome. Additional ovarian cancer molecular subtyping using gene expression analysis may provide more reliable data.

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Section: Discussionmentioning

confidence: 99%

Hormone Receptor, HER2/NEU and EGFR Expression in Ovarian Carcinoma - is here a Prognostic Phenotype?

Demir¹,

Yiğit²,

Sadullahoğlu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…1 Nevertheless, molecularbased subtype classification of breast cancer using these three molecules alone is insufficient to reflect the complex biological characteristics of the disease or meet the need for personalized care. 1,[6][7][8][9] For example, about one third of hormone receptor-positive patients benefit little from endocrine therapy according to current criteria. 1,5,10 Further, some hormone receptor-positive patients with a potentially better prognosis are subjected to intensive chemotherapy but suffer from toxicity (overtreatment), while other patients at high risk of recurrence receive inadequate treatment, leading to compromised efficacy (undertreatment).…”

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confidence: 99%

Subtype classification for prediction of prognosis of breast cancer from a biomarker panel: correlations and indications

Chen¹,

Yuan²,

Wen³

et al. 2014

IJN

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Background Hormone receptors, including the estrogen receptor and progesterone receptor, human epidermal growth factor receptor 2 (HER2), and other biomarkers like Ki67, epidermal growth factor receptor (EGFR, also known as HER1), the androgen receptor, and p53, are key molecules in breast cancer. This study evaluated the relationship between HER2 and hormone receptors and explored the additional prognostic value of Ki67, EGFR, the androgen receptor, and p53. Methods Quantitative determination of HER2 and EGFR was performed in 240 invasive breast cancer tissue microarray specimens using quantum dot (QD)-based nanotechnology. We identified two subtypes of HER2, ie, high total HER2 load (HTH2) and low total HER2 load (LTH2), and three subtypes of hormone receptor, ie, high hormone receptor (HHR), low hormone receptor (LHR), and no hormone receptor (NHR). Therefore, breast cancer patients could be divided into five subtypes according to HER2 and hormone receptor status. Ki67, p53, and the androgen receptor were determined by traditional immunohistochemistry techniques. The relationship between hormone receptors and HER2 was investigated and the additional value of Ki67, EGFR, the androgen receptor, and p53 for prediction of 5-year disease-free survival was assessed. Results In all patients, quantitative determination showed a statistically significant ( P <0.001) negative correlation between HER2 and the hormone receptors and a significant positive correlation ( P <0.001) between the estrogen receptor and the progesterone receptor ( r =0.588), but a significant negative correlation ( P <0.001, r =−0.618) with the HHR subtype. There were significant differences between the estrogen receptor, progesterone receptor, and HER2 subtypes with regard to total HER2 load and hormone receptor subtypes. The rates of androgen receptor and p53 positivity were 46.3% and 57.0%, respectively. Other than the androgen receptor, differences in expression of Ki67, EGFR, and p53 did not achieve statistical significance ( P >0.05) between the five subtypes. EGFR and Ki67 had prognostic significance for 5-year disease-free survival in univariate analysis, but the androgen receptor and p53 did not. Multivariate analysis identified that EGFR expression had predictive significance for 5-year disease-free survival in hormone-receptor positive patients and in those with the lymph node-positive breast cancer subtype. Conclusion Hormone receptor expression was indeed one of the molecular profiles in the subtypes identified by quantitative HER2 and vice versa. EGFR status may provide discriminative prognostic information in addition to HER2 and hormone receptor status, and should be integrated into routine practice to help formulate more specific prediction of the prognosis and appropr...

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“…The epidermal growth factor receptor (EGFR) is a member of the ErbB receptor family and is a new therapeutic target in solid tumors. 2 To date, four members of the ErbB receptor family have been identified, including EGFR (HER1/ErbB-1), HER2 (ErbB-2/neu), HER3 (ErbB-3), and HER4 (ErbB-4). These ErbB receptors are widely expressed in several mammalian tissues and cell types, particularly those of epithelial, mesenchymal, and neuronal origin.…”

Section: Introductionmentioning

confidence: 99%

“…They participate actively in physiological functions, such as cell proliferation and differentiation, cellcell interaction, cytokine signaling and stress responses, and in oncological activities, such as cancer cell proliferation, survival, and metastasis. 2,3 Structurally, EGFR is a transmembrane protein with an extracellular epidermal growth factor-binding domain, a transmembrane region, and an intracellular domain with ligand-activated tyrosine kinase activity. EGFR has been identified as a key cell surface receptor involved in a complex signaling network, with a binding capacity to various classes of agonists, including epidermal growth factor, transforming growth factor alpha, heparin-binding epidermal growth factor-like growth factor, amphiregulin, epiregulin, epigen, betacellulin, and neuregulin 2β.…”

Section: Introductionmentioning

confidence: 99%

Quantum dot-based quantitative immunofluorescence detection and spectrum analysis of epidermal growth factor receptor in breast cancer tissue arrays

Yang

Chen²,

Peng³

et al. 2011

IJN

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Background:The epidermal growth factor receptor (EGFR) is a promising therapeutic target in cancer, but its clinical value in breast cancer remains controversial. Our previous studies have found that quantitative analysis of biomarkers with quantum dot-based nanotechnology had better detection performance than conventional immunohistochemistry. The present study was undertaken to investigate the prognostic value of EGFR in breast cancer using quantum dot-based quantitative spectral analysis. Methods: EGFR expression in 65 breast cancer specimens was detected by immunohistochemistry and quantum dot-immunohistochemistry, and comparisons were made between the two methods. EGFR expression in tissue microarrays of 240 breast cancer patients was then detected by quantum dot-immunohistochemistry and spectral analysis. The prognostic value of EGFR immunofluorescence area (EGFR area) for five-year recurrence-free survival was investigated. Results: The same antigen localization, high correlation of staining rates (r = 0.914), and high agreement of measurement (κ = 0.848) of EGFR expression in breast cancer were found by quantum dot-immunohistochemistry and immunohistochemistry. The EGFR area showed significant differences by tumor grade, lymph node status, HER2 status, and hormone receptor status (all P , 0.05). Patients in the large EGFR area ($30.51) group had a significantly higher five-year recurrence rate (47.2% versus 27.4%, P = 0.002) and worse five-year recurrence-free survival (log-rank test, P = 0.0015) than those in the small EGFR area (,30.51) group. In the subgroups, EGFR area was an independent prognosticator in the HER2-positive and lymph node-positive subgroups. Conclusion: Quantum dot-based quantitative detection demonstrates the prognostic value of EGFR area in the HER2-positive and lymph node-positive subgroups of invasive breast cancer.

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ErbB family receptor inhibitors as therapeutic agents in breast cancer: Current status and future clinical perspective

Cited by 76 publications

References 272 publications

Hormone Receptor, HER2/NEU and EGFR Expression in Ovarian Carcinoma - is here a Prognostic Phenotype?

Hormone Receptor, HER2/NEU and EGFR Expression in Ovarian Carcinoma - is here a Prognostic Phenotype?

Subtype classification for prediction of prognosis of breast cancer from a biomarker panel: correlations and indications

Quantum dot-based quantitative immunofluorescence detection and spectrum analysis of epidermal growth factor receptor in breast cancer tissue arrays

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