mRNA expression of specific HER ligands and their association with clinical outcome in patients with metastatic breast cancer treated with trastuzumab

Rapti,Vassiliki; Moirogiorgou,Evangelia; Koliou,Georgia-Angeliki; Papadopoulou,Kyriaki; Binas,Ioannis; Pentheroudakis,George; Bafaloukos,Dimitrios; Bobos,Mattheos; Chatzopoulos,Kyriakos; Chrisafi,Sofia; Christodoulou,Christos; Nicolaou,Irene; Sotiropoulou,Maria; Magkou,Christina; Koutras,Angelos; Papakostas,Pavlos; Kotsakis,Athanasios; Razis,Evangelia; Psyrri,Amanda; Tryfonopoulos,Dimitrios; Pectasides,Dimitrios; Res,Eleni; Alexopoulos,Athanasios; Kotoula,Vassiliki; Fountzilas,George

doi:10.3892/ol.2021.13141

mRNA expression of specific HER ligands and their association with clinical outcome in patients with metastatic breast cancer treated with trastuzumab

Authors:
- Vassiliki Rapti
- Evangelia Moirogiorgou
- Georgia-Angeliki Koliou
- Kyriaki Papadopoulou
- Ioannis Binas
- George Pentheroudakis
- Dimitrios Bafaloukos
- Mattheos Bobos
- Kyriakos Chatzopoulos
- Sofia Chrisafi
- Christos Christodoulou
- Irene Nicolaou
- Maria Sotiropoulou
- Christina Magkou
- Angelos Koutras
- Pavlos Papakostas
- Athanasios Kotsakis
- Evangelia Razis
- Amanda Psyrri
- Dimitrios Tryfonopoulos
- Dimitrios Pectasides
- Eleni Res
- Athanasios Alexopoulos
- Vassiliki Kotoula
- George Fountzilas
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Affiliations: Second Department of Internal Medicine, Agios Savvas Cancer Hospital, 11522 Athens, Greece, Oncology Department, Hygeia Hospital, 15123 Athens, Greece, Section of Biostatistics, Hellenic Cooperative Oncology Group, 11526 Athens, Greece, Laboratory of Molecular Oncology, Hellenic Foundation for Cancer Research/Aristotle University of Thessaloniki, 54006 Thessaloniki, Greece, Second Department of Medical Oncology, Metropolitan Hospital, 18547 Piraeus, Greece, Department of Medical Oncology, Medical School, University of Ioannina, 45500 Ioannina, Greece, First Department of Medical Oncology, Metropolitan Hospital, 18547 Piraeus, Greece, Department of Histopathology, Agii Anargiri Cancer Hospital, 14564 Athens, Greece, Department of Pathology, Alexandra Hospital, 11528 Athens, Greece, Pathology Department, Evangelismos Hospital, 10676 Athens, Greece, Division of Oncology, Department of Medicine, University Hospital, University of Patras Medical School, 26504 Patras, Greece, Oncology Unit, Hippokration Hospital, 11527 Athens, Greece, Department of Medical Oncology, University Hospital of Heraklion School of Medicine, University of Crete, 71500 Crete, Greece, Third Department of Medical Oncology, Hygeia Hospital, 15123 Athens, Greece, Section of Medical Oncology, Department of Internal Medicine, Attikon University Hospital, Faculty of Medicine, National and Kapodistrian University of Athens School of Medicine, 12462 Athens, Greece, Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, 11527 Athens, Greece, Third Department of Medical Oncology, Agii Anargiri Cancer Hospital, Kifissia 14564 Athens, Greece
Published online on: November 17, 2021 https://doi.org/10.3892/ol.2021.13141
Article Number: 23

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Abstract

Prognostic and predictive biomarkers are being studied for the diagnosis and treatment of breast cancer. The present study retrospectively assessed the mRNA expression of HER family receptor ligands and of other potential prognostic biomarkers and their association with time to progression (TTP), survival and clinicopathological characteristics in patients with metastatic breast cancer (MBC) treated with trastuzumab. A total of 145 tumour tissue samples were analysed. mRNA expression analysis of the transcripts of interest was performed and the association of these markers with selected clinicopathological parameters was examined. HER2 status was centrally re‑evaluated. Only 67.6% of patients were truly HER2‑positive according to the central HER2 re‑evaluation. Heparin binding epidermal growth factor (EGF)‑like growth factor, transforming growth factor β1 (TGFB1) and thyroid hormone receptor α (THRA) mRNA expression was higher in HER2‑positive patients (P=0.026, P<0.001 and P<0.001). Insulin‑like growth factor binding protein 4 was correlated with retinoic acid receptor α, TGFB1 and THRA (rho=0.45, rho=0.60 and rho=0.45). In HER2‑positive patients, high neuregulin 1 and high betacellulin were unfavourable factors for TTP [hazard ratio (HR) = 1.78, P=0.040 and HR=2.00, P=0.043, respectively]. In patients with de novo MBC, high EGF expression was associated with a non‑significant prolongation of TTP (HR=0.52, P=0.080) and significantly longer survival (HR=0.40, P=0.020). The present study examined clinical and biological implications of specific genes and it was concluded that their expression has an impact on the outcome of trastuzumab‑treated patients with MBC.

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