PMID- 38104247
OWN - NLM
STAT- MEDLINE
DCOM- 20240502
LR  - 20240509
IS  - 1943-7722 (Electronic)
IS  - 0002-9173 (Linking)
VI  - 161
IP  - 5
DP  - 2024 May 2
TI  - HER2/ERBB2 copy number analysis by targeted next-generation sequencing in breast 
      cancer.
PG  - 436-442
LID - 10.1093/ajcp/aqad167 [doi]
AB  - OBJECTIVES: A combination of immunohistochemistry (IHC) and fluorescence in situ 
      hybridization (FISH) is the current standard of care for HER2 evaluation in 
      breast cancer. Here, we investigate the potential clinical utility of 
      next-generation sequencing (NGS)-derived HER2/ERBB2 copy number (CN) data for 
      predicting HER2 status as defined by American Society of Clinical Oncology 
      (ASCO)/College of American Pathologists (CAP) guidelines. METHODS: In total, 294 
      locally recurrent and metastatic breast cancers previously tested by targeted 
      hybrid capture-based NGS and by HER2 IHC/FISH were included. Analyses focused on 
      the ERBB2 median log2 ratios and start-end genomic coordinates from NGS, average 
      HER2 CN and HER2/CEP17 ratios from FISH, and the HER2 IHC scores. We also 
      determined a more stringent log2 ratio cutoff to predict HER2-positive status 
      with 100% specificity. RESULTS: Sixty-four (22%) cases were HER2 positive and 230 
      (78%) were HER2 negative by ASCO/CAP guidelines. The ERBB2 median log2 ratios 
      from NGS strongly correlated with HER2 status by IHC/FISH (area under receiver 
      operator characteristic curve = 0.951). ERBB2 log2 ratio more than 1.7 was 100% 
      specific for HER2-positive results by IHC/FISH. Start and end genomic coordinates 
      for regions of gain near ERBB2 by NGS also predicted HER2 status. CONCLUSIONS: 
      Copy number data from our NGS panel strongly correlate with HER2 status. Using a 
      stringent cutoff, ERBB2 log2 ratio accurately predicts HER2 positivity with high 
      specificity. The NGS CN assessment may have utility in determining HER2 status in 
      certain clinical settings.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of American 
      Society for Clinical Pathology. All rights reserved. For commercial re-use, 
      please contact reprints@oup.com for reprints and translation rights for reprints. 
      All other permissions can be obtained through our RightsLink service via the 
      Permissions link on the article page on our site-for further information please 
      contact journals.permissions@oup.com.
FAU - Xia, Daniel
AU  - Xia D
AUID- ORCID: 0000-0003-3825-0577
AD  - Department of Pathology, University Health Network, Toronto,Canada.
FAU - Kuo, Frank
AU  - Kuo F
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, MA, US.
FAU - Hughes, Melissa
AU  - Hughes M
AD  - Breast Oncology, Dana Farber Cancer Institute, Boston, MA, US.
FAU - Lindeman, Neal
AU  - Lindeman N
AD  - Pathology & Laboratory Medicine, Weill Cornell Medicine, New York, NY, US.
FAU - Manning, Danielle
AU  - Manning D
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, MA, US.
FAU - Files, Janet
AU  - Files J
AD  - Breast Oncology, Dana Farber Cancer Institute, Boston, MA, US.
FAU - Strauss, Sarah
AU  - Strauss S
AD  - Breast Oncology, Dana Farber Cancer Institute, Boston, MA, US.
FAU - Kirkner, Greg
AU  - Kirkner G
AD  - Breast Oncology, Dana Farber Cancer Institute, Boston, MA, US.
FAU - Mohammed-Abreu, Ayesha
AU  - Mohammed-Abreu A
AD  - Breast Oncology, Dana Farber Cancer Institute, Boston, MA, US.
FAU - Winer, Eric
AU  - Winer E
AD  - Yale Cancer Center, New Haven, CT, US.
FAU - Tolaney, Sara M
AU  - Tolaney SM
AD  - Breast Oncology, Dana Farber Cancer Institute, Boston, MA, US.
FAU - Lin, Nancy U
AU  - Lin NU
AD  - Breast Oncology, Dana Farber Cancer Institute, Boston, MA, US.
FAU - Dillon, Deborah A
AU  - Dillon DA
AD  - Department of Pathology, Brigham and Women's Hospital, Boston, MA, US.
LA  - eng
GR  - Specialized Program of Research Excellence/
GR  - Dana-Farber Cancer Institute Breast Oncology Center/
GR  - Harvard Cancer Center/
PT  - Journal Article
PL  - England
TA  - Am J Clin Pathol
JT  - American journal of clinical pathology
JID - 0370470
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - 0 (Biomarkers, Tumor)
SB  - IM
MH  - Humans
MH  - Female
MH  - *Breast Neoplasms/genetics/pathology
MH  - *Receptor, ErbB-2/genetics/analysis
MH  - *High-Throughput Nucleotide Sequencing/methods
MH  - *In Situ Hybridization, Fluorescence
MH  - *DNA Copy Number Variations
MH  - Immunohistochemistry
MH  - Gene Dosage
MH  - Biomarkers, Tumor/genetics
MH  - Middle Aged
OTO - NOTNLM
OT  - ERBB2
OT  - FISH
OT  - HER2
OT  - breast cancer
OT  - copy number
OT  - immunohistochemistry
OT  - next-generation sequencing
EDAT- 2023/12/17 09:46
MHDA- 2024/05/02 06:42
CRDT- 2023/12/17 03:29
PHST- 2023/06/18 00:00 [received]
PHST- 2023/11/13 00:00 [accepted]
PHST- 2024/05/02 06:42 [medline]
PHST- 2023/12/17 09:46 [pubmed]
PHST- 2023/12/17 03:29 [entrez]
AID - 7476680 [pii]
AID - 10.1093/ajcp/aqad167 [doi]
PST - ppublish
SO  - Am J Clin Pathol. 2024 May 2;161(5):436-442. doi: 10.1093/ajcp/aqad167.