Evaluation of the Role of p95 HER2 Isoform in Trastuzumab Efficacy in Metastatic Breast Cancer.
Adult
Aged
Aged, 80 and over
Antineoplastic Agents, Immunological
/ therapeutic use
Breast Neoplasms
/ drug therapy
Drug Resistance, Neoplasm
Female
Gene Expression Regulation, Neoplastic
Humans
Isoenzymes
Ki-67 Antigen
/ metabolism
Middle Aged
Neoplasm Metastasis
Progression-Free Survival
Receptor, ErbB-2
/ antagonists & inhibitors
Retrospective Studies
Trastuzumab
/ therapeutic use
HER2
Trastuzumab
breast cancer
p95
Journal
Anticancer research
ISSN: 1791-7530
Titre abrégé: Anticancer Res
Pays: Greece
ID NLM: 8102988
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
received:
19
01
2021
revised:
05
03
2021
accepted:
08
03
2021
entrez:
4
4
2021
pubmed:
5
4
2021
medline:
14
4
2021
Statut:
ppublish
Résumé
Human epidermal growth factor receptor 2 (HER2) P95-isoform could be involved in trastuzumab resistance in HER2 metastatic breast cancer. A total of 114 metastatic breast cancer patients treated with trastuzumab were evaluated retrospectively. HER2 was centrally reviewed. P95 was evaluated along with other markers possibly affecting trastuzumab efficacy in regards to progression-free survival and overall survival. HER2 was centrally negative in 54 cases. P95 expression was significantly higher in HER2-positive tumors. High p95 was associated with gain of HER2 copy number variations (CNVs), high pHER2Tyr877, Ki67 and HER2 mRNA. P95 as a continuous variable was positively correlated with mRNA expression of HER2 and negatively correlated with HER4 and IGF1. HER2-negative p95-high patients had a marginally higher risk for death (HR=2.15, p=0.055). p95 was associated with higher HER2 CNVs and mRNA expression, pHER2Tyr877 expression and high Ki67, indicating a more aggressive phenotype.
Sections du résumé
BACKGROUND/AIM
OBJECTIVE
Human epidermal growth factor receptor 2 (HER2) P95-isoform could be involved in trastuzumab resistance in HER2 metastatic breast cancer.
MATERIALS AND METHODS
METHODS
A total of 114 metastatic breast cancer patients treated with trastuzumab were evaluated retrospectively. HER2 was centrally reviewed. P95 was evaluated along with other markers possibly affecting trastuzumab efficacy in regards to progression-free survival and overall survival.
RESULTS
RESULTS
HER2 was centrally negative in 54 cases. P95 expression was significantly higher in HER2-positive tumors. High p95 was associated with gain of HER2 copy number variations (CNVs), high pHER2Tyr877, Ki67 and HER2 mRNA. P95 as a continuous variable was positively correlated with mRNA expression of HER2 and negatively correlated with HER4 and IGF1. HER2-negative p95-high patients had a marginally higher risk for death (HR=2.15, p=0.055).
CONCLUSION
CONCLUSIONS
p95 was associated with higher HER2 CNVs and mRNA expression, pHER2Tyr877 expression and high Ki67, indicating a more aggressive phenotype.
Identifiants
pubmed: 33813384
pii: 41/4/1793
doi: 10.21873/anticanres.14945
doi:
Substances chimiques
Antineoplastic Agents, Immunological
0
Isoenzymes
0
Ki-67 Antigen
0
MKI67 protein, human
0
ERBB2 protein, human
EC 2.7.10.1
Receptor, ErbB-2
EC 2.7.10.1
Trastuzumab
P188ANX8CK
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1793-1802Informations de copyright
Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.