Integrated genomic characterization of ERBB2/HER2 alterations in invasive breast carcinoma: a focus on unusual FISH groups

Yang, Soo‐Ryum; Bouhlal, Yosr; Vega, Francisco; Ballard, Morgan; Kuo, Calvin J.; Vilborg, Anna; Jensen, Greg; Allison, Kimberly H.

doi:10.1038/s41379-020-0504-5

Cited by 13 publications

(15 citation statements)

References 31 publications

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“…investigated the concordance between ERBB2 copy number alterations, HER2 FISH, and HER2 IHC; however, the study was not limited to cases with equivocal HER2 results. The group found one of 17 (6%) cases with 2018 ASCO/CAP Group 4 results and ERBB2 amplification detected with NGS, although, in that case, HER2 IHC showed 3+ staining 16 …”

Section: Discussionmentioning

confidence: 97%

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Next‐generation assessment of human epidermal growth factor receptor 2 gene (ERBB2) amplification status in invasive breast carcinoma: a focus on Group 4 by use of the 2018 American Society of Clinical Oncology/College of American Pathologists HER2 testing guideline

et al. 2020

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Aims The American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) updated the testing guideline in 2018 to address issues arising from uncommon human epidermal growth factor receptor 2 (HER2) fluorescence in‐situ hybridisation (FISH) results according to the 2013 guideline. Next‐generation sequencing (NGS) may be used to better classify patients. The aim of this study was to assess the ERBB2 amplification status of invasive breast carcinoma with equivocal HER2 immunohistochemistry (IHC) results by using NGS, focusing on Group 4 (HER2/CEP17 ratio of <2.0; average HER2 signals/cell of ≥4.0 and <6.0). Methods and results We retrospectively reviewed HER2 FISH and NGS data of HER2 IHC‐equivocal breast carcinomas at our centre between January 2009 and September 2019, wherein all three assays were performed on the same tissue block, and compared HER2 FISH results, according to the 2018 ASCO/CAP guideline, and the ERBB2 amplification status determined with NGS. A total of 52 HER2 FISH and NGS results from 51 patients with HER2 IHC‐equivocal breast carcinomas were reviewed. The cohort included eight cases classified as 2018 ASCO/CAP in‐situ hybridisation Group 1, three classified as Group 2, three classified as Group 3, 14 classified as Group 4, and 24 classified as Group 5. Thirteen of 14 (92.9%) Group 4 (HER2‐negative) cases were classified as ERBB2‐non‐amplified by the use of NGS; the discordant case was later classified as Group 1 with alternative sample FISH testing. NGS revealed no significant difference in somatic mutations or copy number alterations between Groups 4 and 5. Conclusions Our NGS findings support the reclassification of HER2 FISH‐equivocal cases as HER2‐negative under the 2018 ASCO/CAP guideline.

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Section: Discussionmentioning

confidence: 97%

“…Studies comparing HER2 FISH and NGS for ERBB2 copy number remain limited. Yang et al 16 . investigated the concordance between ERBB2 copy number alterations, HER2 FISH, and HER2 IHC; however, the study was not limited to cases with equivocal HER2 results.…”

Section: Discussionmentioning

confidence: 99%

Next‐generation assessment of human epidermal growth factor receptor 2 gene (ERBB2) amplification status in invasive breast carcinoma: a focus on Group 4 by use of the 2018 American Society of Clinical Oncology/College of American Pathologists HER2 testing guideline

et al. 2020

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“…As suggested in a previous study, only if the HER2 /CEP17 ratio was two or higher and the HER2 signals/cells was six or higher (group 1A) was this considered a true positive. Only four of these 16 cases did not agree with the results of the clinical methods and NGS for ERBB2 amplification [ 11 ].…”

Section: Resultsmentioning

confidence: 99%

“…In contrast, groups 2–4 showed unusual patterns, but there remained a lack of evidence of a response to anti-HER2 treatment. According to a study by Yang et al [ 11 ], for these unusual ISH groups, few cases showed a copy number gain in NGS among ISH groups 2–4, and even this was limited to the cases of IHC 3+. In particular, when group 1 was divided into group 1A with HER2 signals/cell ≥ 6.0 and group 1B with HER2 signals/cell ≥ 4.0 and < 6.0, there was a significant difference between 1A and 1B with regard to the ERBB2 copy number levels in NGS.…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Data of a Next-Generation Sequencing Panel from K-MASTER Project with That of Orthogonal Methods for Detecting Targetable Genetic Alterations

Choi

Kim

et al. 2022

Cancer Res Treat

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K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods. Materials and MethodsColorectal, breast, non-small-cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer (CRC); EGFR, ALK fusion, and ROS1 fusion in non-small-cell lung cancer (NSCLC), and ERBB2 positivity in breast and gastric cancers). ResultsIn the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively. ConclusionThe results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.

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“…Accurate and quantitative evaluation of HER2 copy number is the precondition to assess the dose-response or prognostic effect of HER2 copy number in HER2 positive breast cancer treated with trastuzumab. Although multiple approaches have been reported in HER2 copy number detection, such as chromogenic in site hybridization (CISH) [ 11 ], silver in site hybridization (SISH) [ 12 ], multiplex ligation dependent probe amplification (MLPA) [ 13 ], droplet digital PCR (ddPCR) and next generation sequencing (NGS) [ 14 ], FISH has been recommended as the gold standard of HER2 copy number detection. However, it is also expensive and time consuming [ [15] , [16] , [17] ].…”

Section: Introductionmentioning

confidence: 99%

HER2 copy number quantification in primary tumor and cell-free DNA provides additional prognostic information in HER2 positive early breast cancer

et al. 2022

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Integrated genomic characterization of ERBB2/HER2 alterations in invasive breast carcinoma: a focus on unusual FISH groups

Cited by 13 publications

References 31 publications

Next‐generation assessment of human epidermal growth factor receptor 2 gene (ERBB2) amplification status in invasive breast carcinoma: a focus on Group 4 by use of the 2018 American Society of Clinical Oncology/College of American Pathologists HER2 testing guideline

Next‐generation assessment of human epidermal growth factor receptor 2 gene (ERBB2) amplification status in invasive breast carcinoma: a focus on Group 4 by use of the 2018 American Society of Clinical Oncology/College of American Pathologists HER2 testing guideline

Comparison of the Data of a Next-Generation Sequencing Panel from K-MASTER Project with That of Orthogonal Methods for Detecting Targetable Genetic Alterations

HER2 copy number quantification in primary tumor and cell-free DNA provides additional prognostic information in HER2 positive early breast cancer

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