RESUMO
BACKGROUND: Hormone and human epidermal growth factor receptor 2 (HER2) receptors are the most important breast cancer biomarkers, and additional objective and quantitative test methods such as messenger RNA (mRNA)-based quantitative analysis are urgently needed. In this study, we investigated the clinical validity of RT-PCR-based evaluation of estrogen receptor (ESR1) and HER2 mRNA expression. PATIENTS AND METHODS: A total of 1050 core biopsies from two retrospective (GeparTrio, GeparQuattro) and one prospective (PREDICT) neoadjuvant studies were evaluated by quantitative RT-PCR for ESR1 and HER2. RESULTS: ESR1 mRNA was significantly predictive for reduced response to neoadjuvant chemotherapy in univariate and multivariate analysis in all three cohorts. The complete pathologically documented response (pathological complete response, pCR) rate for ESR1+/HER2- tumors was 7.3%, 8.0% and 8.6%; for ESR1-/HER2- tumors it was 34.4%, 33.7% and 37.3% in GeparTrio, GeparQuattro and PREDICT, respectively (P < 0.001 in each cohort). In the Kaplan-Meier analysis in GeparTrio patients with ESR1+/HER2- tumors had the best prognosis, compared with ESR1-/HER2- and ESR1-/HER2+ tumors [disease-free survival (DFS): P < 0.0005, overall survival (OS): P < 0.0005]. CONCLUSIONS: Our results suggest that mRNA levels of ESR1 and HER2 predict response to neoadjuvant chemotherapy and are significantly associated with long-term outcome. As an additional option to standard immunohistochemistry and gene-array-based analysis, quantitative RT-PCR analysis might be useful for determination of the receptor status in breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Receptor alfa de Estrogênio/genética , Receptor ErbB-2/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Ductal de Mama/mortalidade , Receptor alfa de Estrogênio/metabolismo , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise Multivariada , Terapia Neoadjuvante , Estudos Prospectivos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Receptor ErbB-2/metabolismo , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Resultado do TratamentoRESUMO
A multitude of prognostic and predictive multiparameter algorithms based on the analysis of mRNA have been published in recent years. Many of the algorithms require fresh or fresh frozen tissue as a source of the mRNA. However, practical considerations suggest formalin-fixed paraffin-embedded tissue (FFPE tissue) to be a more suitable starting material for routine diagnostic applications. Therefore, Siemens Healthcare Diagnostics is developing a fully automated method to extract mRNA and DNA from FFPE tissue for use in pathology laboratories. Initially, the method will be used as part of a prognosis assay to predict the likelihood of distant metastasis and death for node-negative breast cancer patients.