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Research ArticleExperimental Studies

Evaluation of the Role of p95 HER2 Isoform in Trastuzumab Efficacy in Metastatic Breast Cancer

GEORGIOS RIGAKOS, EVANGELIA RAZIS, GEORGIA-ANGELIKI KOLIOU, GEORGIOS OIKONOMOPOULOS, ELEFTHERIA TSOLAKI, JEFF SPERINDE, SOFIA CHRISAFI, GEORGE ZARKAVELIS, ELISSAVET PAZARLI, ANNA BATISTATOU, HELEN P. KOUREA, PAVLOS PAPAKOSTAS, DIMITRIOS BAFALOUKOS, NATALIA I. ASIMAKOPOULOU, ELENI RES, ATHANASIOS KOTSAKIS, DIMITRIOS PECTASIDES, ANGELOS KOUTRAS, CHRISTOS CHRISTODOULOU and GEORGE FOUNTZILAS
Anticancer Research April 2021, 41 (4) 1793-1802; DOI: https://doi.org/10.21873/anticanres.14945
GEORGIOS RIGAKOS
1Third Department of Medical Oncology, Hygeia Hospital, Athens, Greece;
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  • For correspondence: grigakos@oncologists.gr
EVANGELIA RAZIS
1Third Department of Medical Oncology, Hygeia Hospital, Athens, Greece;
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GEORGIA-ANGELIKI KOLIOU
2Section of Biostatistics, Hellenic Cooperative Oncology Group, Data Office, Athens, Greece;
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GEORGIOS OIKONOMOPOULOS
3Second Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece;
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ELEFTHERIA TSOLAKI
4Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece;
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JEFF SPERINDE
5Monogram Biosciences, Laboratory Corporation of America Holdings, South San Francisco, CA, U.S.A.;
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SOFIA CHRISAFI
4Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece;
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GEORGE ZARKAVELIS
6Department of Medical Oncology, University Hospital of Ioannina, Ioannina, Greece;
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ELISSAVET PAZARLI
7Department of Pathology, Papageorgiou Hospital, Aristotle University of Thessaloniki, School of Health Sciences, Faculty of Medicine, Thessaloniki, Greece;
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ANNA BATISTATOU
8Department of Pathology, Ioannina University Hospital, Ioannina, Greece;
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HELEN P. KOUREA
9Department of Pathology, University Hospital of Patras, Rion, Greece;
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PAVLOS PAPAKOSTAS
10Oncology Unit, Hippokration Hospital, Athens, Greece;
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DIMITRIOS BAFALOUKOS
11First Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece;
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NATALIA I. ASIMAKOPOULOU
1Third Department of Medical Oncology, Hygeia Hospital, Athens, Greece;
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ELENI RES
12Third Department of Medical Oncology, Agii Anargiri Cancer Hospital, Athens, Greece;
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ATHANASIOS KOTSAKIS
13University Hospital of Heraklion School of Medicine, University of Crete, Heraklion, Greece;
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DIMITRIOS PECTASIDES
14Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, Athens, Greece;
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ANGELOS KOUTRAS
15Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, Patras, Greece;
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CHRISTOS CHRISTODOULOU
3Second Department of Medical Oncology, Metropolitan Hospital, Piraeus, Greece;
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GEORGE FOUNTZILAS
4Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, Thessaloniki, Greece;
16Aristotle University of Thessaloniki, Thessaloniki, Greece;
17German Oncology Center, Limassol, Cyprus
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Abstract

Background/Aim: Human epidermal growth factor receptor 2 (HER2) P95-isoform could be involved in trastuzumab resistance in HER2 metastatic breast cancer. Materials and 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: 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: p95 was associated with higher HER2 CNVs and mRNA expression, pHER2Tyr877 expression and high Ki67, indicating a more aggressive phenotype.

Key Words:
  • Trastuzumab
  • p95
  • breast cancer
  • HER2
  • Received January 19, 2021.
  • Revision received March 5, 2021.
  • Accepted March 8, 2021.
  • Copyright © 2021 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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Anticancer Research: 41 (4)
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Evaluation of the Role of p95 HER2 Isoform in Trastuzumab Efficacy in Metastatic Breast Cancer
GEORGIOS RIGAKOS, EVANGELIA RAZIS, GEORGIA-ANGELIKI KOLIOU, GEORGIOS OIKONOMOPOULOS, ELEFTHERIA TSOLAKI, JEFF SPERINDE, SOFIA CHRISAFI, GEORGE ZARKAVELIS, ELISSAVET PAZARLI, ANNA BATISTATOU, HELEN P. KOUREA, PAVLOS PAPAKOSTAS, DIMITRIOS BAFALOUKOS, NATALIA I. ASIMAKOPOULOU, ELENI RES, ATHANASIOS KOTSAKIS, DIMITRIOS PECTASIDES, ANGELOS KOUTRAS, CHRISTOS CHRISTODOULOU, GEORGE FOUNTZILAS
Anticancer Research Apr 2021, 41 (4) 1793-1802; DOI: 10.21873/anticanres.14945

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Evaluation of the Role of p95 HER2 Isoform in Trastuzumab Efficacy in Metastatic Breast Cancer
GEORGIOS RIGAKOS, EVANGELIA RAZIS, GEORGIA-ANGELIKI KOLIOU, GEORGIOS OIKONOMOPOULOS, ELEFTHERIA TSOLAKI, JEFF SPERINDE, SOFIA CHRISAFI, GEORGE ZARKAVELIS, ELISSAVET PAZARLI, ANNA BATISTATOU, HELEN P. KOUREA, PAVLOS PAPAKOSTAS, DIMITRIOS BAFALOUKOS, NATALIA I. ASIMAKOPOULOU, ELENI RES, ATHANASIOS KOTSAKIS, DIMITRIOS PECTASIDES, ANGELOS KOUTRAS, CHRISTOS CHRISTODOULOU, GEORGE FOUNTZILAS
Anticancer Research Apr 2021, 41 (4) 1793-1802; DOI: 10.21873/anticanres.14945
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