PMID- 31482108
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20231013
IS  - 2374-4677 (Print)
IS  - 2374-4677 (Electronic)
IS  - 2374-4677 (Linking)
VI  - 5
DP  - 2019
TI  - Quantitative assessments and clinical outcomes in HER2 equivocal 2018 ASCO/CAP 
      ISH group 4 breast cancer.
PG  - 28
LID - 10.1038/s41523-019-0122-x [doi]
LID - 28
AB  - We quantified human epidermal growth factor receptor 2 (HER2) RNA and protein 
      expression in 2018 American Society of Clinical Oncology/College of American 
      Pathologists (ASCO/CAP) in situ hybridization (ISH) group 4 (HER2/centromeric 
      probe 17 (CEP17) ratio <2.0, average HER2 copy number >/=4.0 and <6.0, and 2013 
      ASCO/CAP ISH equivocal) breast cancers. Breast cancers in 2018 ASCO/CAP ISH group 
      4 between 2014 and 2017 were identified from the Yale archives. Sixty-three 
      patients (34 with HER2 immunohistochemistry (IHC) 0/1+ and 29 with HER2 IHC 2+) 
      were included. We compared patient characteristics, systemic treatments, and 
      outcomes. We assessed HER2 by real-time quantitative reverse transcription 
      polymerase chain reaction (RT-qPCR) and quantitative immunofluorescence (QIF). 
      Among ISH group 4 cancers, higher HER2 mRNA (P < 0.0001) but similar HER2 protein 
      levels were observed in IHC 2+ compared to IHC 0/1+ cancers. The distribution of 
      RT-qPCR and QIF scores were independent of fluorescence in situ hybridization 
      (FISH) ratio/copy number. Concordance between HER2 RT-qPCR and QIF was 69.8% 
      (r = 0.52). Among 29 patients with IHC2+ results, 16 were HER2 positive by 
      RT-qPCR and 12 were HER2 positive by QIF. Systemic treatment, recurrence, and 
      survival outcomes were comparable among ISH group 4 cancers regardless of IHC 
      0/1+ or 2+ results. ISH group 4 cancers appear to form a distinct group with 
      intermediate levels of RNA/protein expression, close to positive/negative cut 
      points. Therefore, adjudication into positive or negative categories may not be 
      meaningful. Our results support the 2018 ASCO/CAP recommendation to refrain from 
      routine additional testing of these samples. Additional outcome information after 
      trastuzumab treatment for patients in this special group might help to guide 
      treatment decisions in these patients.
FAU - Gupta, Swati
AU  - Gupta S
AD  - 1Department of Pathology, Yale University School of Medicine, New Haven, CT USA. 
      ISNI: 0000000419368710. GRID: grid.47100.32
FAU - Neumeister, Veronique
AU  - Neumeister V
AD  - 1Department of Pathology, Yale University School of Medicine, New Haven, CT USA. 
      ISNI: 0000000419368710. GRID: grid.47100.32
AD  - Indivumed Inc, Frederick, MD USA.
FAU - McGuire, John
AU  - McGuire J
AD  - 1Department of Pathology, Yale University School of Medicine, New Haven, CT USA. 
      ISNI: 0000000419368710. GRID: grid.47100.32
FAU - Song, Yan S
AU  - Song YS
AD  - 1Department of Pathology, Yale University School of Medicine, New Haven, CT USA. 
      ISNI: 0000000419368710. GRID: grid.47100.32
FAU - Acs, Balazs
AU  - Acs B
AUID- ORCID: 0000-0002-0972-4633
AD  - 1Department of Pathology, Yale University School of Medicine, New Haven, CT USA. 
      ISNI: 0000000419368710. GRID: grid.47100.32
AD  - 3Department of Oncology and Pathology, Karolinska Institute, Stockholm, Sweden. 
      ISNI: 0000 0004 1937 0626. GRID: grid.4714.6
FAU - Ho, Kenneth
AU  - Ho K
AD  - 4Division of Oncology Research and Development, Cepheid, Sunnyvale, CA USA. GRID: 
      grid.433548.d
FAU - Weidler, Jodi
AU  - Weidler J
AD  - 5Medical and Scientific Affairs and Strategy, Oncology, Cepheid, Sunnyvale, CA 
      USA. GRID: grid.433548.d
FAU - Wong, Wendy
AU  - Wong W
AD  - 4Division of Oncology Research and Development, Cepheid, Sunnyvale, CA USA. GRID: 
      grid.433548.d
FAU - Rhees, Brian
AU  - Rhees B
AD  - 4Division of Oncology Research and Development, Cepheid, Sunnyvale, CA USA. GRID: 
      grid.433548.d
FAU - Bates, Michael
AU  - Bates M
AD  - 5Medical and Scientific Affairs and Strategy, Oncology, Cepheid, Sunnyvale, CA 
      USA. GRID: grid.433548.d
FAU - Rimm, David L
AU  - Rimm DL
AUID- ORCID: 0000-0001-5820-4397
AD  - 1Department of Pathology, Yale University School of Medicine, New Haven, CT USA. 
      ISNI: 0000000419368710. GRID: grid.47100.32
FAU - Bossuyt, Veerle
AU  - Bossuyt V
AD  - 6Massachusetts General Hospital, Boston, MA USA. ISNI: 0000 0004 0386 9924. GRID: 
      grid.32224.35
LA  - eng
PT  - Journal Article
DEP - 20190829
PL  - United States
TA  - NPJ Breast Cancer
JT  - NPJ breast cancer
JID - 101674891
PMC - PMC6715641
OTO - NOTNLM
OT  - Breast cancer
OT  - Cancer
COIS- Competing interestsD.L.R. is a consultant/advisor to Amgen, Astra Zeneca, 
      Agendia, Biocept, Biocept, BMS, Cell Signaling Technology, Cepheid, Daiichi 
      Sankyo, GSK, InVicro/Konica Minolta, Merck, Perkin Elmer, PAIGE.AI, and Ultivue. 
      K.H., J.W., W.W., B.R., and M.B. are employees of Cepheid. The other authors 
      declare no competing interests.
EDAT- 2019/09/05 06:00
MHDA- 2019/09/05 06:01
PMCR- 2019/08/29
CRDT- 2019/09/05 06:00
PHST- 2019/01/22 00:00 [received]
PHST- 2019/07/29 00:00 [accepted]
PHST- 2019/09/05 06:00 [entrez]
PHST- 2019/09/05 06:00 [pubmed]
PHST- 2019/09/05 06:01 [medline]
PHST- 2019/08/29 00:00 [pmc-release]
AID - 122 [pii]
AID - 10.1038/s41523-019-0122-x [doi]
PST - epublish
SO  - NPJ Breast Cancer. 2019 Aug 29;5:28. doi: 10.1038/s41523-019-0122-x. eCollection 
      2019.