PMID- 32805517
OWN - NLM
STAT- MEDLINE
DCOM- 20210713
LR  - 20211002
IS  - 1532-8198 (Electronic)
IS  - 1092-9134 (Print)
IS  - 1092-9134 (Linking)
VI  - 48
DP  - 2020 Oct
TI  - Clinicopathologic features of breast cancer reclassified as HER2-amplified by 
      fluorescence in situ hybridization with alternative chromosome 17 probes.
PG  - 151576
LID - S1092-9134(20)30119-2 [pii]
LID - 10.1016/j.anndiagpath.2020.151576 [doi]
AB  - OBJECTIVE: Dual probe fluorescence in situ hybridization (FISH) assays for 
      determination of human epidermal growth factor receptor 2 (HER2) gene 
      amplification in breast cancer provide a ratio of HER2 to chromosome 17. The 
      ratio may be skewed by copy number alterations (CNA) in the control locus for 
      chromosome 17 (CEP17). We analyzed the impact of alternative chromosome 17 
      control probes on HER2 status in a series of breast cancers with an emphasis on 
      patients reclassified as amplified. METHODS: Breast cancer patients with 
      equivocal HER2 immunohistochemistry (2+) and equivocal FISH with CEP17 were 
      included. Reclassification of HER2 status was assessed with alternative 
      chromosome 17 control probes (LIS1 and RARA). RESULTS: A total of 40 unique 
      patients with 46 specimens reflexed to alternative chromosome 17 probe testing 
      were identified. The majority (>80%) of patients had pT1-2, hormone 
      receptor-positive tumors with an intermediate or high combined histologic grade. 
      There were 34/46 (73.9%) specimens reclassified as amplified with alternative 
      probes, corresponding to 29/40 (72.5%) patients. Of the patients reclassified as 
      amplified with alternative probes, 34.5% (10/29) received HER2-targeted therapy. 
      CONCLUSION: In this series, the majority of breast cancers tested with 
      alternative chromosome 17 control probes under the 2013 ASCO/CAP Guidelines were 
      converted to HER2-amplified. The treatment data and the clinicopathologic profile 
      of the tumors suggest that most of these patients will neither receive nor 
      benefit from HER2-targeted therapy. The findings support the recommendation in 
      the 2018 ASCO/CAP HER2 Guidelines to discontinue the use of alternative 
      chromosome 17 probes.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Blanton, Kristen C
AU  - Blanton KC
AD  - School of Medicine, University of North Carolina, Chapel Hill, NC, USA.
FAU - Deal, Allison M
AU  - Deal AM
AD  - Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel 
      Hill, NC, USA.
FAU - Kaiser-Rogers, Kathleen A
AU  - Kaiser-Rogers KA
AD  - Department of Pathology and Laboratory Medicine, University of North Carolina, 
      Chapel Hill, NC, USA.
FAU - Anders, Carey K
AU  - Anders CK
AD  - Department of Medicine, Division of Medical Oncology, Duke Cancer Institute, 
      Durham, NC, USA.
FAU - O'Connor, Siobhan M
AU  - O'Connor SM
AD  - Department of Pathology and Laboratory Medicine, University of North Carolina, 
      Chapel Hill, NC, USA.
FAU - Hertel, Johann D
AU  - Hertel JD
AD  - Department of Pathology and Laboratory Medicine, University of North Carolina, 
      Chapel Hill, NC, USA.
FAU - Calhoun, Benjamin C
AU  - Calhoun BC
AD  - Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel 
      Hill, NC, USA; Department of Pathology and Laboratory Medicine, University of 
      North Carolina, Chapel Hill, NC, USA. Electronic address: 
      ben.calhoun@unchealth.unc.edu.
LA  - eng
GR  - P30 CA016086/CA/NCI NIH HHS/United States
GR  - T35 DK007386/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20200808
PL  - United States
TA  - Ann Diagn Pathol
JT  - Annals of diagnostic pathology
JID - 9800503
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (Biomarkers, Tumor)
RN  - EC 2.7.10.1 (ERBB2 protein, human)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - P188ANX8CK (Trastuzumab)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Antineoplastic Agents, Immunological/metabolism/therapeutic use
MH  - Biomarkers, Tumor/genetics
MH  - Breast Neoplasms/classification/metabolism/*pathology/therapy
MH  - Chromosomes, Human, Pair 17/*metabolism
MH  - DNA Copy Number Variations/genetics
MH  - Female
MH  - Humans
MH  - In Situ Hybridization, Fluorescence/*methods
MH  - Medical Oncology/organization & administration
MH  - Middle Aged
MH  - Molecular Targeted Therapy/statistics & numerical data
MH  - Neoplasm Grading/methods
MH  - Practice Guidelines as Topic
MH  - Receptor, ErbB-2/*metabolism
MH  - Retrospective Studies
MH  - Societies, Medical/organization & administration
MH  - Trastuzumab/metabolism/therapeutic use
MH  - United States
PMC - PMC7907993
MID - NIHMS1671503
OTO - NOTNLM
OT  - ASCO/CAP guidelines
OT  - Breast
OT  - Chromosome 17
OT  - FISH
OT  - HER2
COIS- Declaration of competing interest Dr. Anders receives research funding from PUMA, 
      Lilly, Merck, Seattle Genetics, Nektar, Tesaro, G1-Therapeutics; compensation as 
      a consultant for Genentech (1/2019-), Eisai (1/2019-), IPSEN (2/2019 -), Seattle 
      Genetics (11/15/2019-11/15/2020); and royalties from UpToDate and Jones and 
      Bartlett. Dr. Calhoun is a member of the Oncology Advisory Board for Luminex 
      Corporation. The other authors have no relevant financial disclosures.
EDAT- 2020/08/18 06:00
MHDA- 2021/07/14 06:00
PMCR- 2021/10/01
CRDT- 2020/08/18 06:00
PHST- 2020/06/15 00:00 [received]
PHST- 2020/06/19 00:00 [accepted]
PHST- 2020/08/18 06:00 [pubmed]
PHST- 2021/07/14 06:00 [medline]
PHST- 2020/08/18 06:00 [entrez]
PHST- 2021/10/01 00:00 [pmc-release]
AID - S1092-9134(20)30119-2 [pii]
AID - 10.1016/j.anndiagpath.2020.151576 [doi]
PST - ppublish
SO  - Ann Diagn Pathol. 2020 Oct;48:151576. doi: 10.1016/j.anndiagpath.2020.151576. 
      Epub 2020 Aug 8.