Evaluation of the prognostic value of all four HER family receptors in patients with metastatic breast cancer treated with trastuzumab: A Hellenic Cooperative Oncology Group (HeCOG) study
Autor: | Georgia-Angeliki Koliou, George Pentheroudakis, Kalliopi Petraki, Evangelia Razis, Eleftheria Tsolaki, Angelos Koutras, George Kouvatseas, Dimitrios Bafaloukos, Georgios Lazaridis, Vassiliki Kotoula, Anna Batistatou, Kyriaki Papadopoulou, Stavroula Pervana, Dimitrios Pectasides, Haralambos P. Kalofonos, Pavlos Papakostas, George Fountzilas, Sofia Chrisafi, Amanda Psyrri, Konstantine T. Kalogeras, Mattheos Bobos, Christos Christodoulou |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Oncology Receptor ErbB-4 Receptor ErbB-3 Receptor ErbB-2 Protein Expression Cancer Treatment Gene Expression Antineoplastic Agents Immunological 0302 clinical medicine Trastuzumab Breast Tumors Medicine and Health Sciences RNA Neoplasm Neoplasm Metastasis skin and connective tissue diseases In Situ Hybridization Fluorescence Staining Aged 80 and over education.field_of_study Multidisciplinary Fluorescent in Situ Hybridization medicine.diagnostic_test biology Middle Aged Prognosis Immunohistochemistry Metastatic breast cancer Membrane Staining ErbB Receptors 030220 oncology & carcinogenesis Medicine Female Research Article medicine.drug Adult medicine.medical_specialty DNA Copy Number Variations Class I Phosphatidylinositol 3-Kinases Science Population Molecular Probe Techniques Breast Neoplasms Research and Analysis Methods 03 medical and health sciences Breast cancer Internal medicine Breast Cancer Gene Expression and Vector Techniques Genetics medicine Humans PTEN RNA Messenger Molecular Biology Techniques education Molecular Biology Immunohistochemistry Techniques neoplasms Aged Retrospective Studies Molecular Biology Assays and Analysis Techniques business.industry Gene Amplification PTEN Phosphohydrolase Biology and Life Sciences Cancers and Neoplasms Retrospective cohort study medicine.disease Probe Hybridization Histochemistry and Cytochemistry Techniques 030104 developmental biology Specimen Preparation and Treatment Immunologic Techniques biology.protein business Cytogenetic Techniques Cloning Fluorescence in situ hybridization |
Zdroj: | PLoS ONE PLoS ONE, Vol 13, Iss 12, p e0207707 (2018) |
ISSN: | 1932-6203 |
Popis: | In the current study, we performed a complete analysis, with four different methods, of all four HER family receptors, in a series of patients with metastatic breast cancer treated with trastuzumab-based regimens and evaluated their prognostic value. Formalin-fixed paraffin-embedded tumor tissue samples were collected from 227 patients, considered to be HER2-positive when assessed at the local laboratories. We evaluated gene amplification, copy number variations (CNVs), mRNA and protein expression of all four HER family members. In addition, our analysis included the evaluation of several other factors by immunohistochemistry (IHC), such as pHER2Tyr1221/1222, pHER2Tyr877 and PTEN. Central review of HER2 status by IHC and fluorescence in situ hybridization revealed that of the 227 patients, only 139 (61.2%) were truly HER2-positive. Regarding the 191 patients treated with trastuzumab as first-line therapy, median time to progression (TTP) was 15.3 and 10.4 months for HER2-positive and HER2-negative participants, respectively, whereas median survival was 50.4 and 38.1 months, respectively. In HER2-positive patients, high HER3 mRNA expression was of favorable prognostic significance for TTP and survival (HR = 0.43, 95% CI 0.21-0.88, Wald's p = 0.022 and HR = 0.43, 95% CI 0.21-0.88, p = 0.021, respectively), while EGFR copy gain and EGFR protein expression were associated with higher risk for disease progression in HER2-negative patients (HR = 3.53, 95% CI 1.19-10.50, p = 0.023 and HR = 3.37, 95% CI 1.12-10.17, p = 0.031, respectively). Positive HER3 protein expression was a favorable factor for TTP in HER2-negative patients (HR = 0.43, 95% CI 0.22-0.84, p = 0.014). In the multivariate analysis, only EGFR copy gain retained its prognostic significance for TTP in the HER2-negative population (HR = 3.96, 95% CI 1.29-12.16, p = 0.016), while high HER3 mRNA expression retained its favorable prognostic significance for TTP in the HER2-positive subgroup (HR = 0.47, 95% CI 0.23-0.99, p = 0.048). The present study suggests that EGFR copy gain represents a negative prognostic factor for TTP in HER2-negative patients with metastatic breast cancer treated with trastuzumab. In addition, high HER3 mRNA expression appears to be of favorable prognostic significance for TTP in HER2-positive patients. Given the small number of patients included in the current analysis and the retrospective nature of the study, our findings should be validated in larger cohorts. |
Databáze: | OpenAIRE |
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