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
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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