Central validation of HER2 status to determine heterogeneity of marker expression in HER2-positive gastric cancer (GC).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 12-12
Author(s):  
Ivonne Haffner ◽  
Birgit Luber ◽  
Dieter Maier ◽  
Albrecht Kretzschmar ◽  
Ludwig Fischer von Weikersthal ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Her2 Status ◽  
Her2 Gene ◽  
Her2 Positive ◽  
Secondary Resistance ◽  
Deviation Rate ◽  
Epidermal Growth ◽  
Egfr Family

12 Background: 10-20% of GC overexpress HER2, a membrane-bound receptor tyrosine kinase (RTK) which belongs to the epidermal growth factor receptor (EGFR) family. Drugs directed against HER2 have shown mixed success in the treatment of advanced GC. While trastuzumab, a monoclonal antibody addressing HER2 has been approved for 1st-line treatment of stage IV HER2+ GC, trastuzumab-emtansine failed to improve outcomes in 2nd-line and lapatinib, a small molecular RTK inhibitor of HER2 and EGFR was not effective in 1st- and 2nd-line. Until now, primary and secondary resistance against HER2-directed treatment of GC is not well understood. The VARIANZ study aims to assess mechanisms influencing efficacy of trastuzumab in HER2+ GC. Methods: In this multicenter study, patients who receive medical treatment for advanced GC are recruited in 31 sites. The HER2 status is verified centrally by two dedicated GI pathologists using immunohistochemistry (IHC, DCS, HI608C0I) and chromogenic-in-situ hybridization (CISH, Zytomed Systems, C-3022-40). Results: From May 2014 to August 2016, we have enrolled 316 patients in this ongoing project (72% male, median age 64 years). At present, 281 samples were fully characterized for the HER2 status. According to criteria from the Trastuzumab for Gastric Cancer (ToGA) study, 53 of 281 samples were characterized HER2+ by central testing. In 38 samples that were diagnosed as HER2+ by local pathologists the HER2 status could not be verified centrally. 7 HER2- probes in local testing were characterized as HER2+ by central testing. The overall deviation rate between local and central testing is 27%. HER2 gene amplification in HER2+ tumors with deviating local report (mean HER2/CEP17: 2.8 ± 0.9, range between 1.9 and 4.5) is lower compared to HER2+ tumors and confirmed local report (mean HER2/CEP17: 5.5 ± 2.6; range between 2.2 and 11.0; p = 0.014). Conclusions: HER2-expression in GC is heterogeneous and still not easy to assess. Variability between local and central HER2 assessment is significant. Robust biomarkers predicting response or resistance to HER2 and other target therapies are needed. Clinical trial information: NCT02305043.

Reagent-saving immunohistochemistry for HER2 using non-contact alternating current electric field mixing

2018 ◽  
Vol 72 (1) ◽  
pp. 25-30 ◽  
Author(s):  
Iku Hoshino ◽  
Kazuhiro Imai ◽  
Hiroshi Nanjo ◽  
Ryuta Nakamura ◽  
Yoshitaro Saito ◽  
...  
Keyword(s):  
Electric Field ◽  
Growth Factor Receptor ◽  
Alternating Current ◽  
Her2 Status ◽  
Breast Cancers ◽  
Clinical Tool ◽  
Her2 Positive ◽  
Specific Staining ◽  
Epidermal Growth ◽  
Current Electric Field

AimsHuman epidermal growth factor receptor 2 (HER2)-targeted agents are an effective approach to treating patients with HER2-positive breast cancer. However, the lack of survival benefit in HER2-negative patients, as well as the toxic effects and high cost of the drugs, highlight the need for accurate and prompt assessment of HER2 status. Our aim was to evaluate the clinical utility of a novel reagent-saving immunohistochemistry method (AC-IHC) that saves HER2 antibody by taking advantage of the non-contact mixing effect in microdroplets subjected to an alternating current electric field.MethodsNinety-five specimens were used from patients diagnosed with primary breast cancers identified immunohistochemically as HER2 0/1+, 2+ or 3+ using ASCO/CAP guideline-certified standard IHC. The specimens were all tested using the conventional IHC method (1:50 antibody dilution) as well as AC-IHC (1:50 dilution) and reagent-saving AC-IHC (1:100 dilution).ResultsThe reagent-saving AC-IHC produced stable results with less non-specific staining using smaller amounts of labelled antibody. Moreover, the staining and accuracy of HER2 status evaluated with the reagent-saving AC-IHC method was equal to that achieved with standard IHC.ConclusionsThese results suggest reagent-saving AC-IHC could be used as a clinical tool for accurate and stable HER2 IHC, even when reagent concentrations vary.

Efficacy results from the ToGA trial: A phase III study of trastuzumab added to standard chemotherapy (CT) in first-line human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (GC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. LBA4509-LBA4509 ◽  
Author(s):  
E. Van Cutsem ◽  
Y. Kang ◽  
H. Chung ◽  
A. Sawaki ◽  
F. Lordick ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor Receptor ◽  
Phase Iii ◽  
First Line ◽  
Standard Chemotherapy ◽  
Her2 Positive ◽  
Phase Iii Study ◽  
Epidermal Growth ◽  
Final Text

LBA4509 The full, final text of this abstract will be available in Part II of the 2009 ASCO Annual Meeting Proceedings, distributed onsite at the Meeting on May 30, 2009, and as a supplement to the June 20, 2009, issue of the Journal of Clinical Oncology. [Table: see text]

Human Epidermal Growth Factor Receptor 2 Assessment in a Case-Control Study: Comparison of Fluorescence In Situ Hybridization and Quantitative Reverse Transcription Polymerase Chain Reaction Performed by Central Laboratories

2010 ◽  
Vol 28 (28) ◽  
pp. 4300-4306 ◽  
Author(s):  
Frederick L. Baehner ◽  
Ninah Achacoso ◽  
Tara Maddala ◽  
Steve Shak ◽  
Charles P. Quesenberry ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Oncotype Dx ◽  
Her2 Status ◽  
Rt Pcr ◽  
Her2 Positive ◽  
Polysomy 17 ◽  
Epidermal Growth ◽  
Polymerase Chain ◽  
Control Study

Purpose The optimal method to assess human epidermal growth factor receptor 2 (HER2) status remains highly controversial. Before reporting patient HER2 results, American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines mandate that laboratories demonstrate ≥ 95% concordance to another approved laboratory or methodology. Here, we compare central laboratory HER2 assessed by fluorescence in situ hybridization (FISH) and quantitative reverse transcriptase polymerase chain reaction (RT-PCR) using Oncotype DX in lymph node–negative, chemotherapy-untreated patients from a large Kaiser Permanente case-control study. Patients and Methods Breast cancer specimens from the Kaiser–Genomic Health study were examined. Central FISH assessment of HER2 amplification and polysomy 17 was conducted by PhenoPath Laboratories (ratios > 2.2, 1.8 to 2.2, and < 1.8 define HER2 positive, HER2 equivocal, and HER2 negative, respectively). HER2 expression by RT-PCR was conducted using Oncotype DX by Genomic Health (normalized expression units ≥ 11.5, 10.7 to < 11.5, and < 10.7 define HER2 positive, HER2 equivocal, and HER2 negative, respectively). Concordance analyses followed ASCO/CAP guidelines. Results HER2 concordance by central FISH and central RT-PCR was 97% (95% CI, 96% to 99%). Twelve percent (67 of 568 patients) and 11% (60 of 568 patients) of patients were HER2 positive by RT-PCR and FISH, respectively. HER2-positive patients had increased odds of dying from breast cancer compared with HER2-negative patients. Polysomy 17 was demonstrated in 12.5% of all patients and 33% of FISH-positive patients. Nineteen of 20 FISH-positive patients with polysomy 17 were also RT-PCR HER2 positive. Although not statistically significantly different, HER2-positive/polysomy 17 patients tended to have the worst prognosis, followed by HER2-positive/eusomic, HER2-negative/polysomy 17, and HER2-negative/eusomic patients. Conclusion There is a high degree of concordance between central FISH and quantitative RT-PCR using Oncotype DX for HER2 status, and the assay warrants additional study in a trastuzumab-treated population.

scholarly journals Immunohistochemical Study on Hormone Receptors and HER2 Status in Invasive Breast Carcinoma and its Therapeutic Implications

2019 ◽  
Vol 7 (2) ◽  
pp. 95-98
Author(s):  
Md Iqbal Karim ◽  
Md Tarikul Islam ◽  
Nazlima Nargis
Keyword(s):  
Breast Carcinoma ◽  
Hormone Receptors ◽  
Growth Factor Receptor ◽  
Inverse Correlation ◽  
Chemotherapeutic Agents ◽  
Her2 Status ◽  
Her2 Positive ◽  
Therapeutic Implications ◽  
Epidermal Growth

Background: Immunohistochemistry (IHC) has become an integral part of histopathology in the diagnosis of biopsysample. Although haematoxylin and eosin (H & E) stain remains the fundamental basis for diagnostic pathology of thebreast, IHC stains provide useful and sometimes vital information. Moreover, the role of hormonal therapy in hormonereceptor–positive breast tumours, as well as targeted chemotherapeutic agents for human epidermal growth factorreceptor-2 (HER2) positive cases, IHC studies represent a major part of workups. Objective: The study was carried out to identify the common immunohistochemical markers in invasive breastcarcinoma and to find out the relationship between hormonal receptor status and HER2 over expression with the gradeof tumour and its therapeutic implications. Method: In the present study, immunohistochemical assay of total seventy-two blocks of breast carcinoma patients wasperformed to know the hormone receptors and HER2 status as well as histological examination. Result: 72 samples were grouped to study hormonal status and their relation with clinicopathological factors. Outcomeof this study documented 58.33 %, 44.44% and 25 % expression rate of estrogen receptor (ER), progesterone receptor(PR) and human epidermal growth factor receptor-2 (HER2) respectively. The negative expression of HER2 receptorsfound higher (75%) than ER & PR. The ER, PR negative and HER2 Positive cases found in high grade breast cancer(Grade-3). An inverse correlation of HER2 expression with ER and PR expression was observed (p=0.001). Conclusion: The role of hormone receptors and HER2 repression as a prognostic and therapeutic tool in breast canceris widely accepted and effective for patients. Bangladesh Crit Care J September 2019; 7(2): 95-98

scholarly journals Loss of Human Epidermal Growth Factor Receptor 2 (HER2) Expression in Metastatic Sites of HER2-Overexpressing Primary Breast Tumors

2012 ◽  
Vol 30 (6) ◽  
pp. 593-599 ◽  
Author(s):  
Naoki Niikura ◽  
Jun Liu ◽  
Naoki Hayashi ◽  
Elizabeth A. Mittendorf ◽  
Yun Gong ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Epidermal Growth Factor Receptor ◽  
Growth Factor ◽  
Growth Factor Receptor ◽  
Breast Tumors ◽  
Her2 Status ◽  
Her2 Positive ◽  
Metastatic Tumors ◽  
Epidermal Growth

Purpose We evaluated whether patients with human epidermal growth factor receptor 2 (HER2) –positive primary breast tumors had metastatic tumors that were HER2 positive (concordant) or HER2 negative (discordant). We then evaluated whether treatment with trastuzumab or chemotherapy before biopsy of the metastasis had any effect on the rate of HER2 discordance. We also compared the overall survival durations of patients with HER2-concordant and -discordant tumors. Patients and Methods We retrospectively identified all patients who initially had been diagnosed with HER2-positive (immunohistochemistry 3+ and/or fluorescent in situ hybridization positive) primary breast cancer between 1997 and 2008 at MD Anderson Cancer Center who also had metastatic tumor biopsy results available for review. Results We included 182 patients who met our criteria. Forty-three (24%) of the 182 patients with HER2-positive primary tumors had HER2-negative metastatic tumors. The HER2 discordance rates differed significantly on the basis of whether patients received chemotherapy (P = .022) but not on the basis of whether patients received trastuzumab (P = .296). Patients with discordant HER2 status had shorter overall survival than did patients with concordant HER2 status (hazard ratio [HR], 0.43; P = .003). A survival difference remained among the 67 patients who received trastuzumab (HR, 0.56; P = .083) and 101 patients who did not (HR, 0.53; P = .033) before their metastasis biopsies. Conclusion We confirmed that loss of HER2-positive status in metastatic tumors can occur in patients with primary HER2-positive breast cancer. Our data strongly support the need for biopsies of metastatic lesions to accurately determine patient prognosis and appropriate use of targeted therapy.

scholarly journals Hyperprogressive Disease in the Irradiation Field after a Single Dose of Nivolumab for Gastric Cancer: A Case Report

2018 ◽  
Vol 11 (1) ◽  
pp. 143-150 ◽  
Author(s):  
Takatsugu Ogata ◽  
Hironaga Satake ◽  
Misato Ogata ◽  
Yukimasa Hatachi ◽  
Hisateru Yasui
Keyword(s):  
Gastric Cancer ◽  
Checkpoint Inhibitors ◽  
Gastroesophageal Junction ◽  
Growth Factor Receptor ◽  
Stage Iv ◽  
Rapid Progression ◽  
Gastroesophageal Cancer ◽  
Irradiation Field ◽  
Epidermal Growth ◽  
Hyperprogressive Disease

Following the ATTRACTION-2 study, nivolumab was approved for advanced gastric cancer in Japan. However, pseudoprogression and hyperprogressive disease have been reported in patients treated with immune checkpoint inhibitors. We report a patient with gastric cancer who received nivolumab after radiotherapy only to experience rapid progression within the irradiation field after the first immunotherapy session. A 66-year-old man with dysphagia visited our hospital and was diagnosed with stage IV gastroesophageal cancer (human epidermal growth factor receptor-2 score = 0). He commenced a G-SOX regimen (S-1 80 mg/m2 on days 1–14 and oxaliplatin 100 mg/m2 on day 1, repeated every 3 weeks) in June 2017. The dysphagia worsened despite 3 cycles of G-SOX, and computed tomography (CT) revealed constriction of the gastroesophageal junction. To ameliorate the dysphagia, palliative chemoradiotherapy (S-1 and 50.4 Gy in 28 fractions) was performed starting in August 2017. The patient’s dysphagia had not resolved after completing radiotherapy, and pain on swallowing worsened. Nivolumab (3 mg/m2 every 2 weeks) was administered 7 days after the completion of radiotherapy. The patient experienced malaise and worsening dysphagia before the second cycle. CT 15 days after the first nivolumab administration revealed rapid progression in the irradiation field. His general condition rapidly deteriorated, and he died 24 days after the first administration. This episode suggests that administration of nivolumab after radiotherapy may be a risk factor for hyperprogressive disease.

Gastric HER2 testing study (GaTHER): Evaluation of gastric cancer testing accuracy in Australia.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 15-15
Author(s):  
M. P. Kumarasinghe ◽  
A. Morey ◽  
M. Bilous ◽  
S. B. Fox ◽  
Keyword(s):  
Copy Number ◽  
In Situ Hybridisation ◽  
Growth Factor Receptor ◽  
Predictive Marker ◽  
Her2 Status ◽  
Kappa Statistics ◽  
Testing Methods ◽  
Her2 Positive ◽  
Epidermal Growth ◽  
Good Concordance

15 Background: Amplification and/or overexpression of human epidermal growth factor receptor 2 (HER2) has been reported in 6%-33% of advanced gastric cancers (GC), and trastuzumab, an anti-HER2 monoclonal antibody, has been shown to provide a survival benefit in HER2-positive disease. Thus accurate testing will be critical to ensure HER2 utility as a predictive marker in GC. HER2 in situ hybridisation (ISH) testing is currently undertaken for all breast cancer in Australia as part of a national program, however pathologists have limited experience with GC tissue. This study evaluated testing methods and determined inter-laboratory reproducibility of HER2 scoring in GC across 9 Australian reference laboratories. Methods: A tissue microarray (TMA) comprising 100 pre-screened gastric or gastro-oesophageal junction (GOJ) adenocarcinoma samples with a range of HER2 positivity was prepared from 1-mm cores. Each laboratory assessed TMA HER2 status by both immunohistochemistry (IHC) (n=9) and ISH [chromogenic (n=3), silver (n=6), fluorescent (n=1)], using its validated testing methods and applying GC scoring criteria. Inter-laboratory agreement on HER2 ISH scoring, using both HER2 copy number and HER2:chr17 ratio, and agreement on IHC scoring (ToGA method), was calculated (kappa statistics). Results: There was only moderate agreement between laboratories on IHC scoring (κ = 0.46). Agreement on CISH/SISH scoring was good/very good when HER2 copy number, stratified into negative, equivocal and positive for amplification, was used (κ = 0.68-0.86), but was reduced when HER2:chr17 ratio was used (κ = 0.59-0.70). Agreement between CISH/SISH and FISH using HER2 copy number was excellent (κ = 0.88-0.91) but was again reduced when HER2:chr17 ratio was used (κ = 0.84-0.86). Good/very good agreement between IHC and FISH (κ = 0.85) or CISH/SISH (κ = 0.72-0.87) was also achieved when HER2 copy number was used. Conclusions: Good concordance across laboratories can be achieved with FISH, or single-probe CISH or SISH, scored using HER2 copy number, with use of chr17 probe in chromogenic assays best restricted to equivocal cases. HER2 IHC alone is not recommended for determining HER2 status in gastric and GOJ cancers. [Table: see text]

scholarly journals Estrogen receptor, Progesterone receptor, and human epidermal growth factor receptor-2 status in breast cancer: A retrospective study of 5436 women from a regional cancer center in South India

2018 ◽  
Vol 07 (01) ◽  
pp. 07-10 ◽  
Author(s):  
Rekha Vijay Kumar ◽  
Dipti Panwar ◽  
Usha Amirtham ◽  
Chennagiri Srinivasmurthy Premalata ◽  
Champaka Gopal ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Epidermal Growth Factor Receptor ◽  
Retrospective Study ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Growth Factor Receptor ◽  
Her2 Status ◽  
Her2 Positive ◽  
Epidermal Growth

Abstract Aim: The aim of the study was to analyze the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2) status over 7 years in South Indian women with breast cancer. Further analysis of a subgroup was done to study clinically defined subtypes and the role of preanalytical factors in needle core biopsies (NCBs) and excised specimens. Materials and Methods: This was a retrospective study from January 2010 to December 2016. Patients diagnosed with invasive breast cancer and available immunohistochemistry (IHC) reports of ER, PR, and HER2 status were analyzed. The cases for the year 2016 were analyzed further to observe the impact of preanalytical factors on the IHC staining patterns and surrogate status. Results: A total of 5436 patients were included with a median age of 48 years. Among these, 65% were ≤ 55 years. The overall incidence of hormone receptor (HR)-positive patients was 48%; HER2 positive, 15%; and triple-negative breast cancer (TNBC), 37%. The incidence of HR positive, HER2 positive, and TNBC were 45%, 16%, and 39% and 53%, 13%, and 34% in patients <56 years and over 55 years, respectively (P < 0.001). There was an increase in HR positivity and decrease in TNBCs over time. There was no significant difference in the staining patterns in NCBs and excised specimens. Conclusion: With time, there is an increase in hormone-positive tumors which may be attributed to better IHC techniques and tissue handling. There was no statistical difference in the patterns of ER, PR, and HER2 immunostaining in core biopsy and excised specimens.

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