Response of Circulating Tumor Cells to Systemic Therapy in Patients With Metastatic Breast Cancer: Comparison of Quantitative Polymerase Chain Reaction and Immunocytochemical Techniques

Abstract

Circulating carcinoma cells are frequently found in patients with metastatic breast cancer. In the majority of patients, cancer cell numbers as evaluated by QPCR or ICC reflected the outcome of systemic treatment.

Detection of circulating epithelial cells in the blood of patients with breast cancer: comparison of three techniques

“…On this basis, 30% of the patient samples were positive by filtration, 48% by IMS enrichment and 35 -60% using real-time RT -PCR depending on the test gene used. The rates of positive samples using the cytometric techniques and real-time RT -PCR are within the previously observed ranges using such techniques to detect circulating epithelial cells in the blood of patients with metastatic breast cancer (Smith et al, 2000;Bosma et al, 2002;Baker et al, 2003;Stathopoulou et al, 2003;Ring et al, 2004).…”

“…The detection of such cells could have significant clinical utility in risk stratification in early breast cancer, in early detection of relapse and in monitoring response to treatment. Cytometric techniques based on immunohistochemical analyses and nucleic acid-based approaches to cell detection have been described (Racila et al, 1998;Lambrechts et al, 1999;Smith et al, 2000;Aerts et al, 2001;Stathopoulou et al, 2002;Witzig et al, 2002). However, there is considerable variability in the reported sensitivities and specificities of existing techniques with putative carcinoma cells reported to be present in between 0 and 100% of blood samples from patients with metastatic breast cancer (Ring et al, 2004).…”

“…The PCR assay was developed to detect cytokeratin 19 (CK19), mammaglobin and prolactin-inducible peptide (PIP) (Clark et al, 1999), which are expressed in breast epithelial cells but at low levels in normal blood components. CK19 was chosen as it is expressed in the majority of breast cancers (Bartek et al, 1986;Moll, 1994), and has been extensively used in studies in this area (Slade et al, 1999;Smith et al, 2000;Aerts et al, 2001;Stathopoulou et al, 2002Stathopoulou et al, , 2003. Mammaglobin gene expression has previously been used to detect circulating breast cancer micrometastases with no false positives in control populations (Zach et al, 1999;Silva et al, 2002).…”

Effect of different cytokines on mammaglobin and maspin gene expression in normal leukocytes: possible relevance to the assays for the detection of micrometastatic breast cancer

“…Several studies suggest that these objectives can be achieved with the current assays (Cote et al, 1991;Harbeck et al, 1994;Diel et al, 1996;Smith et al, 2000;Terstappen et al, 2000;Gebauer et al, 2001;Jiang et al, 2002;Ozbas et al, 2003;Pantel et al, 2003) and in a few of them the presence of disseminated tumour cells in bone marrow or peripheral blood is recognised as an independent prognostic factor (Diel et al, 1996;Braun et al, 2000;Stathopoulou et al, 2002). However, the literature reports conflicting results and the clinical value of these assays remains to be proven basically because it is uncertain whether the published assays have enough sensitivity, specificity and consistency to be reliably integrated into prospective studies provided with adequate statistical power to answer the most relevant clinical questions (Jiang et al, 2002;Ozbas et al, 2003;Pantel et al, 2003).…”

“…The molecular methods are mainly based on a qualitative reverse transcriptase polymerase chain reaction (RT-PCR) identification of breast tissue-related mRNA sequences and show, in experimental models, a sensitivity in the range of 1 : 10 6 -10 7 , which is generally higher than immunocytochemistry (Smith et al, 2000;Jiang et al, 2002).…”