Phase II of trastuzumab and cisplatin in patients (pts) with advanced gastric cancer (AGC) with HER2/neu overexpression/amplification

Cortés-Funes, H.; Rivera, F.; Ales, Immaculada; Márquez, Arian Benavides; Velasco, A.; Colomer, Ramón; García‐Carbonero, Rocío; Sastre, Javier; Cornejo-Guerra, José Antonio; Grávalos, Cristina

doi:10.1200/jco.2007.25.18_suppl.4613

Cited by 41 publications

(13 citation statements)

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“…16,[45][46][47] This phenomenon could represent a major drawback to sampling tumors for targeted cancer therapy. 2,5,45,46,48,49 In colon and lung cancer, intratumoral heterogeneity of KRAS mutation status is reported and crucial in selecting patients for anti-EGFR therapy. 50,51 It is described that testing DNA from a single sample of colorectal cancer will wrongly assign wild-type status to 10% patients, 50 suggesting multiple sampling in order to improve mutations detection.…”

Section: Discussionmentioning

confidence: 99%

“…2 Recently, treatment with human epidermal growth factor receptor 2 (HER2) inhibitor, Trastuzumab, has been demonstrated to increase overall survival in HER2-positive, inoperable locally advanced or metastatic gastric carcinoma. [3][4][5][6] ERBB2 is a key oncogene in many human cancers since its receptor tyrosine kinase activity triggers crucial intracellular signaling events for cell growth and survival. 7 In gastric cancer, ERBB2 positivity ranges from 7 to 27% of the tumors, [8][9][10][11][12][13] with high concordance rate between overexpression in immunohistochemistry and gene amplification tested by fluorescence in situ hybridization or chromogenic in situ hybridization.…”

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confidence: 99%

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HER2 in gastric cancer: a digital image analysis in pre-neoplastic, primary and metastatic lesions

et al. 2013

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The assessment of human epidermal growth factor receptor 2 (HER2) status in gastric cancer is crucial in selecting patients who may benefit from targeted therapy, yet heterogeneous expression could represent an important drawback for HER2 testing. We aimed to analyze (i) HER2 heterogeneity in primary gastric cancers, pre-neoplastic and metastatic lesions and (ii) HER2 prognostic role. We studied 292 surgically resected primary gastric carcinomas and constructed 21 tissue microarrays including tumor tissue cores, invasive front, paired lymph node metastasis, low-and high-grade dysplasia. Microarrays were immunohistochemically stained with HER2 antibody and digitally scanned. Novel digital analysis algorithms were developed to score HER2 expression. Fluorescence in situ hybridization was performed on equivocal cases. HER2-positive cases were 13% and heterogeneous HER2 expression was observed in 71% of positive samples. Analysis of HER2 status in tumor and tumor invasive front demonstrate concordance in 177 cases (88%). Comparison of HER2 expression in primary cancer and synchronous lymph node metastasis exhibited discordant status in 14% of cases. Dysplastic epithelium surrounding the tumor showed immunohistochemical score 2 or 3 in 19% of high-grade and in 9% of low-grade dysplastic samples. HER2 status was significantly associated with intestinal-type carcinomas (P ¼ 0.018) and prognosis since patients with primary HER2-positive tumor showed decreased overall survival (P ¼ 0.006). Intratumoral HER2 expression heterogeneity and variable lymph node metastases status strongly suggest evaluating more than one sample and, if available, metastatic foci for routinely HER2 testing.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

HER2 in gastric cancer: a digital image analysis in pre-neoplastic, primary and metastatic lesions

et al. 2013

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“…HER2 gene amplification or protein overexpression has been detected in 7-30% of primary gastric adenocarcinomas (2,4,(7)(8)(9). It has been reported that HER2 amplification and overexpression are influenced by the histological type and localisation of tumours (5)(6)(7)(8)(9)(10). Due to technological advances, HER2 can be easily identified; for example immunohistochemistry and fluorescence, chromogenic or silver in situ hybridisation have been used to detect HER2 protein overexpression and gene amplification (11,12).…”

Section: Introductionmentioning

confidence: 99%

Comparing human epidermal growth factor receptor 2 amplification and expression using immunohistochemistry and silver in situ hybridisation in gastric carcinoma and lymph node metastasis

2020

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Detecting the amplification and expression of human epidermal growth factor receptor (HER2) is important for planning trastuzumab treatment for patients with gastric carcinoma. The present study aimed to analyse HER2 amplification and expression in primary gastric adenocarcinoma tumours and metastatic lymph nodes using microarray methods, and to assess the potential contribution of these methods to treatment planning. In total, 60 patients with lymph node metastasis were included in the present study. Microarray blocks were obtained from the tissue blocks of primary tumours and metastatic lymph nodes. HER2 expression and amplification were investigated using immunohistochemical and silver in situ hybridisation (SISH) methods, respectively. Following immunohistochemical evaluation of HER2 in primary tumours, the sensitivity and specificity of the microarray method relative to the single block method were 69 and 100%, respectively. For HER2 detection in microarray block sections from primary tumours, the sensitivity and specificity of the SISH method relative to immunohistochemistry were 56 and 100%, respectively. When using SISH in microarray blocked sections, there was a high degree of concordance (98% concordance rate) between HER2 amplification in the primary tumour and the metastatic lymph node. Furthermore, the sensitivity and specificity of metastatic lymph node results relative to those of the primary tumour were 100 and 98%, respectively. Overall, the single block method was more reliable compared with the microarray method for planning treatment. When microarray blocking was used, a large number of samples must be tested to ensure reliable results. The immunohistochemical method is recommended as the first step as SISH alone increases the risk of false-negative results. Assessing HER2 amplification for treatment planning would be beneficial for primary tumours, as well as metastatic lymph nodes.

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“…The total response rate was only 35%. 24 No grade 4 toxicity related to trastuzumab was reported in any of these trials.…”

Section: Trastuzumab In Esophageal Cancer: the Clinical Aspectmentioning

confidence: 94%

Targeting the Human Epidermal Growth Factor Receptor 2 in Esophageal Cancer

et al. 2013

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The importance of human epidermal growth factor-2 (HER2) in terms of prognosis and aggressiveness of growth has long been known in breast cancer, and interruption of its growth cascade by agents such as trastuzumab and lapatinib has markedly improved outcomes for these patients with HER2 overexpression. HER2 overexpression also occurs in many other tumor types, including esophageal cancer. In this disease, a different scoring system for determining overexpression is used. Limited data exist concerning the biological and therapeutic implications of HER2 overexpression in esophageal cancer. One trial, the so-called ToGA trial, included patients with advanced gastric and gastroesophageal junction (GEJ) tumors that overexpressed HER2. Patients who received trastuzumab plus cisplatin-based chemotherapy had more responses and longer progression-free and overall survival than those who received the chemotherapy alone. Enthusiasm concerning these results must be tempered by the facts that only 25% of the study group had GEJ tumors and, of these, only 33% had HER2 overexpression. Thus, the role of trastuzumab in the management of HER2-overexpressing esophageal cancers remains to be determined. In addition to presenting data on the HER2 cascade, the authors review clinical trials performed to date and also present the validated standard scoring system for HER2 overexpression in esophageal cancer.

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Phase II of trastuzumab and cisplatin in patients (pts) with advanced gastric cancer (AGC) with HER2/neu overexpression/amplification

Cited by 41 publications

References 0 publications

HER2 in gastric cancer: a digital image analysis in pre-neoplastic, primary and metastatic lesions

HER2 in gastric cancer: a digital image analysis in pre-neoplastic, primary and metastatic lesions

Comparing human epidermal growth factor receptor 2 amplification and expression using immunohistochemistry and silver in situ hybridisation in gastric carcinoma and lymph node metastasis

Targeting the Human Epidermal Growth Factor Receptor 2 in Esophageal Cancer

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