TY - JOUR
T1 - Discordance of HER2 Expression and/or Amplification on Repeat Testing
AU - DiPeri, Timothy P.
AU - Kong, Kathleen
AU - Varadarajan, Kaushik
AU - Karp, Daniel D.
AU - Ajani, Jaffer A.
AU - Pant, Shubham
AU - Press, Michael F.
AU - Piha-Paul, Sarina A.
AU - Dumbrava, Ecaterina E.
AU - Meric-Bernstam, Funda
N1 - Publisher Copyright:
© 2023 American Association for Cancer Research Inc.. All rights reserved.
PY - 2023/8/1
Y1 - 2023/8/1
N2 - We sought to assess discordance of HER2 status in patients with HER2 amplified/expressing solid tumors who underwent reevaluation of HER2 status. Patients with metastatic solid tumors and HER2 expression by immunohistochemistry (IHC) or amplification by fluorescent in situ hybridization (FISH)/next generation sequencing (NGS) on local testing underwent central HER2 IHC/FISH testing with either archival or fresh biopsies and were evaluated for discordance in HER2 status. 70 patients (12 cancer types) underwent central HER2 reevaluation, including 57 (81.4%) with a new biopsy. In 30 patients with HER2 3+ on local IHC, 21 (70.0%) were 3+, 5 (16.7%) were 2+, 2 (6.7%) were 1+, and 2 (6.7%) had 0 HER2 expression on central IHC. In 15 patients whose cancers were 2+ on local IHC, 2 (13.3%) were 3+, 5 (33.3%) were 2+, 7 (46.7%) were 1+, and 1 (6.7%) had 0 HER2 expression on central IHC. HER2 discordance was seen in 16 of 52 (30.8%) of patients with HER2 overexpression/amplification who underwent a new image-guided biopsy. Discordance was observed in 10 (33.3%) of 30 patients who received intervening HER2-targeted therapy and in 6 (23.8%) of 22 patients who did not. In the 8 patients who had central HER2 assessment from the same archival block used for local testing, none were discordant. Discordance of HER2 status is common in patients with tumors previously identified as HER2-expressing, especially in patients with HER2 2+ tumors. Repeat biomarker evaluation may have value when considering HER2-targeted therapies.
AB - We sought to assess discordance of HER2 status in patients with HER2 amplified/expressing solid tumors who underwent reevaluation of HER2 status. Patients with metastatic solid tumors and HER2 expression by immunohistochemistry (IHC) or amplification by fluorescent in situ hybridization (FISH)/next generation sequencing (NGS) on local testing underwent central HER2 IHC/FISH testing with either archival or fresh biopsies and were evaluated for discordance in HER2 status. 70 patients (12 cancer types) underwent central HER2 reevaluation, including 57 (81.4%) with a new biopsy. In 30 patients with HER2 3+ on local IHC, 21 (70.0%) were 3+, 5 (16.7%) were 2+, 2 (6.7%) were 1+, and 2 (6.7%) had 0 HER2 expression on central IHC. In 15 patients whose cancers were 2+ on local IHC, 2 (13.3%) were 3+, 5 (33.3%) were 2+, 7 (46.7%) were 1+, and 1 (6.7%) had 0 HER2 expression on central IHC. HER2 discordance was seen in 16 of 52 (30.8%) of patients with HER2 overexpression/amplification who underwent a new image-guided biopsy. Discordance was observed in 10 (33.3%) of 30 patients who received intervening HER2-targeted therapy and in 6 (23.8%) of 22 patients who did not. In the 8 patients who had central HER2 assessment from the same archival block used for local testing, none were discordant. Discordance of HER2 status is common in patients with tumors previously identified as HER2-expressing, especially in patients with HER2 2+ tumors. Repeat biomarker evaluation may have value when considering HER2-targeted therapies.
KW - HER2/neu
KW - biomarker
KW - cancer
KW - oncology
KW - precision
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U2 - 10.1158/1535-7163.MCT-22-0630
DO - 10.1158/1535-7163.MCT-22-0630
M3 - Article
C2 - 37339271
AN - SCOPUS:85170239553
SN - 1535-7163
VL - 22
JO - Molecular cancer therapeutics
JF - Molecular cancer therapeutics
IS - 8
ER -