RESUMO
PURPOSE: We analyzed circulating tumor cells (CTC) in blood of metastatic breast cancer patients (n = 42) and determined the ability of this method to predict therapy response. METHODS: CTC from blood were analyzed before and during therapy for EpCAM, MUC1 and HER2 transcripts with the AdnaTest BreastCancer. The estrogen (ER) and progesterone (PR) receptor expression was assessed by RT-PCR. RESULTS: The overall detection rate for CTC was 52% (thereof 86% EpCAM; 86% MUC1; 32% HER2; 35% ER; 12% PR). CTC were ER, PR and HER2 negative in 45% (ER), 78% (PR) and 60% (HER-2) of patients with steroid receptor-positive tumors. 29% of patients with HER2-negative tumors had HER2-positive CTC. The test predicted therapy response in 78% of all cases. Persistence of CTC significantly correlated with shorter overall survival (P = 0.005). CONCLUSIONS: Molecular profiling of CTC may offer superior prognostic information with regard to risk assessment for recurrence and predictive judgement of therapeutical regimens.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/sangue , Células Neoplásicas Circulantes/metabolismo , Adulto , Idoso , Antígenos de Neoplasias/genética , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/sangue , Carcinoma Ductal de Mama/tratamento farmacológico , Carcinoma Lobular/sangue , Carcinoma Lobular/tratamento farmacológico , Carcinoma Medular/sangue , Carcinoma Medular/tratamento farmacológico , Moléculas de Adesão Celular/genética , Molécula de Adesão da Célula Epitelial , Feminino , Humanos , Técnicas Imunoenzimáticas , Pessoa de Meia-Idade , Mucina-1/genética , Estadiamento de Neoplasias , Prognóstico , Estudos Prospectivos , RNA Mensageiro/genética , Receptor ErbB-2/genética , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de SobrevidaRESUMO
PURPOSE: Retrospective studies have shown that immunoassays measuring free light chains (FLC) in serum are useful for diagnosis and monitoring of multiple myeloma. This study prospectively evaluates the use of FLC assays and, for the first time, investigates the relationship between serum FLC concentrations and the presence and detectability of Bence Jones (BJ) proteins in the urine. PATIENTS AND METHODS: Three hundred seventy-eight paired samples of serum and urine were tested from 82 patients during the course of their disease. The sensitivities of serum FLC analysis and urine immunofixation electrophoresis (IFE) in detecting monoclonal FLC were compared. Serum FLC concentrations required for producing BJ proteins detected by IFE were determined. RESULTS: Abnormal FLC were present in 54% of serum samples compared with 25% by urine tests. In abnormal serum samples for kappa or lambda, the sensitivity of IFE to detect the respective BJ proteins in urine were 51% and 35% and the median serum FLC concentrations required to produce detectable BJ proteins were 113 and 278 mg/L. Renal excretions of monoclonal FLC increased with serum concentrations, but excretions significantly decreased at high serum concentrations combined with renal dysfunction. CONCLUSION: Serum FLC assays are significantly more sensitive for detecting monoclonal FLC than urine IFE analysis. They also have the advantage of FLC quantification and are more reliable for monitoring disease course and response to treatment.