Prevalence of  HER2  Expression and Its Correlation with Clinicopathological Parameters in Gastric or Gastroesophageal Junction Adenocarcinoma in North-East Indian Population

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Abstract

Objective:

Human epidermal growth factor receptor 2 ( erbb2/HER2) overexpression, has now been implicated in advanced gastric and gastroesophageal junction cancers. The study was conducted to determine the rate of HER2 positivity in patients with locally advanced or metastatic gastric and gastroesophageal adenocarcinoma in North-East India and to assess the impact of various demographic and clinical parameters on HER2 positivity.

Methods:

A total of 68 patients of age >18 years of gastric and gastroesophageal adenocarcinoma diagnosed on histopathological examination from September 2016 to February 2018 at Dr B Borooah Cancer Institute, Assam were enrolled for the observational (epidemiological) study. All patients were subjected to the HER2 immunohistochemistry test using a FDA-approved, standardized test kit. HER2 expression was correlated with various demographic and clinicopathological parameters.

Results:

The overall rate of HER2 positivity in the population studied was 56% (n=38). The rate was non-significantly higher in male, older age group (>60 years) and Hindu population. Similarly, HER2 positivity rate was higher in patients with well differentiated histology and was more common in patients with stage II and III diseases, but neither of the associations is statistically significant. HER2 positivity rate was significantly higher in proximal and in GEJ tumours (56% versus 44%, P=0.002).

Conclusion:

HER2 overexpression was evident in 56% of the North-East Indian patients with locally advanced and metastatic gastric and gastroesophageal adenocarcinoma. The overexpression correlated significantly with primary tumour site. Routine testing of gastric and gastroesophageal tumours for HER2 expression is recommended to provide a therapeutic advantage in Indian patients.

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Most cited references 35

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Capecitabine and oxaliplatin for advanced esophagogastric cancer.

David Cunningham, Naureen Starling, Sheela Rao … (2008)

We evaluated capecitabine (an oral fluoropyrimidine) and oxaliplatin (a platinum compound) as alternatives to infused fluorouracil and cisplatin, respectively, for untreated advanced esophagogastric cancer. In a two-by-two design, we randomly assigned 1002 patients to receive triplet therapy with epirubicin and cisplatin plus either fluorouracil (ECF) or capecitabine (ECX) or triplet therapy with epirubicin and oxaliplatin plus either fluorouracil (EOF) or capecitabine (EOX). The primary end point was noninferiority in overall survival for the triplet therapies containing capecitabine as compared with fluorouracil and for those containing oxaliplatin as compared with cisplatin. For the capecitabine-fluorouracil comparison, the hazard ratio for death in the capecitabine group was 0.86 (95% confidence interval [CI], 0.80 to 0.99); for the oxaliplatin-cisplatin comparison, the hazard ratio for the oxaliplatin group was 0.92 (95% CI, 0.80 to 1.10). The upper limit of the confidence intervals for both hazard ratios excluded the predefined noninferiority margin of 1.23. Median survival times in the ECF, ECX, EOF, and EOX groups were 9.9 months, 9.9 months, 9.3 months, and 11.2 months, respectively; survival rates at 1 year were 37.7%, 40.8%, 40.4%, and 46.8%, respectively. In the secondary analysis, overall survival was longer with EOX than with ECF, with a hazard ratio for death of 0.80 in the EOX group (95% CI, 0.66 to 0.97; P=0.02). Progression-free survival and response rates did not differ significantly among the regimens. Toxic effects of capecitabine and fluorouracil were similar. As compared with cisplatin, oxaliplatin was associated with lower incidences of grade 3 or 4 neutropenia, alopecia, renal toxicity, and thromboembolism but with slightly higher incidences of grade 3 or 4 diarrhea and neuropathy. Capecitabine and oxaliplatin are as effective as fluorouracil and cisplatin, respectively, in patients with previously untreated esophagogastric cancer. (Current Controlled Trials number, ISRCTN51678883 [controlled-trials.com].). Copyright 2008 Massachusetts Medical Society.

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HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer

Eric Van Cutsem, Yung-Jue Bang, Feng Feng-yi … (2014)

Background In the Trastuzumab for GAstric cancer (ToGA) study, trastuzumab plus chemotherapy improved median overall survival by 2.7 months in patients with human epidermal growth factor receptor 2 (HER2)-positive [immunohistochemistry (IHC) 3+/fluorescence in situ hybridization-positive] gastric/gastroesophageal junction cancer compared with chemotherapy alone (hazard ratio 0.74). Post hoc exploratory analyses in patients expressing higher HER2 levels (IHC 2+/fluorescence in situ hybridization-positive or IHC 3+) demonstrated a 4.2-month improvement in median overall survival with trastuzumab (hazard ratio 0.65). The ToGA study provides the largest screening dataset available on HER2 overexpression/amplification in this indication. We further analyzed correlation(s) of HER2 overexpression/amplification with clinical and epidemiological factors. Methods HER2-positivity was analyzed by histological subtype, tumor location, geographic region, and specimen type. Exploratory efficacy analyses were performed. Results The HER2-positivity rate was 22.1 % across analyzed tumor samples. Rates were similar between European and Asian patients (23.6 % vs. 23.9 %), but higher in intestinal- vs. diffuse-type (31.8 % vs. 6.1 %), and gastroesophageal junction cancer versus gastric tumors (32.2 % vs. 21.4 %). Across all IHC scores, variability in HER2 staining (≤30 % stained cells) was observed in almost 50 % of cases, with increasing rates in lower IHC categories, and did not affect treatment outcome. The polysomy rate was 4 %. Conclusions HER2 expression varies by tumor location and type. All patients with advanced gastric or gastroesophageal junction cancer should be tested for HER2 status, preferably using IHC initially. Due to the unique characteristics of gastric cancer, specific testing/scoring guidelines should be adhered to. Electronic supplementary material The online version of this article (doi:10.1007/s10120-014-0402-y) contains supplementary material, which is available to authorized users.

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HER2 testing in gastric cancer: a practical approach.

Michael Bilous, Wedad Hanna, Robert Osamura … (2012)

Trastuzumab in combination with capecitabine or 5-fluorouracil and cisplatin is approved by the European Medicines Agency for the treatment of patients with human epidermal growth factor receptor 2 (HER2)-positive (immunohistochemistry 3+ or immunohistochemistry 2+/fluorescence in situ hybridization-positive or immunohistochemistry 2+/silver in situ hybridization-positive) metastatic adenocarcinoma of the stomach or gastro-esophageal junction. Approvals are underway in other countries, with recent approvals granted in the United States and Japan. Experience and data from trastuzumab use in breast cancer have highlighted the importance of quality HER2 testing and scoring to ensure accurate identification of patients eligible for treatment. HER2 testing in gastric cancer differs from testing in breast cancer due to inherent differences in tumor biology; gastric cancer more frequently shows HER2 heterogeneity (focal staining) and incomplete membrane staining. Consequently, gastric cancer-specific HER2 testing protocols have been developed and standardized and it is imperative that these recommendations be adhered to. Given the predictive value of HER2 protein levels with response in the trastuzumab for GAstric cancer study (ToGA), immunohistochemistry should be the initial testing methodology and fluorescence in situ hybridization or silver in situ hybridization should be used to retest immunohistochemistry 2+ samples. Wherever possible, bright-field methodologies should be used as these are considered to be superior to fluorescent methodologies at identifying heterogeneous staining. Specific training is required before embarking on HER2 testing in gastric cancer, irrespective of the experience of HER2 testing in breast cancer. This paper provides the most up-to-date practical guidance on HER2 testing and scoring in patients with gastric and gastro-esophageal junction cancer, as agreed by a panel of expert pathologists with extensive experience of HER2 testing particularly reflecting the European Medicines Agency-approved indication. It is anticipated that these recommendations should ensure accurate and consistent HER2 testing, which will allow appropriate selection of patients eligible for treatment with trastuzumab.

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Author and article information

Journal

Journal ID (nlm-ta): Asian Pac J Cancer Prev

Journal ID (iso-abbrev): Asian Pac. J. Cancer Prev

Journal ID (publisher-id): APJCP

Title: Asian Pacific Journal of Cancer Prevention : APJCP

Publisher: West Asia Organization for Cancer Prevention (Iran )

ISSN (Print): 1513-7368

ISSN (Electronic): 2476-762X

Publication date (Print): 2019

Volume: 20

Issue: 4

Pages: 1139-1145

Affiliations

[1 ] Department of Medical Oncology,

[2 ] Department of Surgical Oncology,

[3 ] Department of Pathology, Dr B Borooah Cancer Institute, Guwahati, Assam, India.

Author notes

[* ]For Correspondence: drmunlimahazarika@yahoo.com

Article

DOI: 10.31557/APJCP.2019.20.4.1139

PMC ID: 6948890

PubMed ID: 31030487

SO-VID: ef0ff865-5a05-4959-9cd5-11d7c21d57eb

License:

This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Prevalence of HER2 Expression and Its Correlation with Clinicopathological Parameters in Gastric or Gastroesophageal Junction Adenocarcinoma in North-East Indian Population

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Karger: Oncology

Most cited references 35

Capecitabine and oxaliplatin for advanced esophagogastric cancer.

HER2 screening data from ToGA: targeting HER2 in gastric and gastroesophageal junction cancer

HER2 testing in gastric cancer: a practical approach.

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