The enumeration of circulating tumour cells (CTCs) with the EpCAM-based CellSearch system has prognostic significance in patients with metastatic breast cancer (MBC). The aim of this study was to ...explore potential differences in the detection and prognostic significance of CTCs in MBC according to immunohistochemical subtypes of breast cancer.
CellSearch CTC counts were obtained from 154 MBC patients before first-line systemic treatment between November 2007 and August 2012. Patients were categorised in five subgroups according to immunohistochemical surrogate definitions of intrinsic subtypes in breast cancer based on hormone receptor status, HER2/neu status and histological grade. Differences in progression-free (PFS) and overall survival (OS) were assessed relative to the cut-off value of ≥5 CTCs per 7.5 ml blood.
No significant differences were observed in the absolute CTC counts (P=0.120) or in CTC positivity rates according to ≥1 and ≥5 CTCs per 7.5 ml blood detection thresholds (P=0.165 and P=0.651, respectively) between immunohistochemical subtypes. However, very high CTC counts, defined as ≥80 CTCs per 7.5 ml, were observed more frequently in patients with Luminal A and triple negative (TN) breast cancer (P=0.024). In the total study population, the presence of ≥5 CTCs was the single most significant prognostic factor for both PFS and OS in multivariate analysis (P<0.001). A more limited prognostic impact, not reaching statistical significance, was observed in patients with HER2-positive disease as opposed to patients with Luminal A, Luminal B-HER2-negative and TN disease.
The detection of EpCAM+CTCs was not clearly associated with any of the immunohistochemical subtypes of breast cancer in patients with MBC before first-line treatment. Potentially clinically relevant differences were however observed at very high CTC counts. Furthermore, our data suggest a lower prognostic significance of CTC evaluation in HER2-positive patients with MBC.
This study assessed the ability of real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis to detect disseminated epithelial cells (DEC) in peripheral blood (PB) and bone marrow ...(BM) of patients with breast cancer (BC). Detection of DEC in BM is an obvious choice in BC, but blood sampling is more convenient. The aim of this study was to evaluate whether the detection of DEC in either PB or BM predicts overall survival (OS). Peripheral blood and BM samples were collected from 148 patients with primary (stage M0, n=116/78%) and metastatic (stage M+, n=32/21%) BC before the initiation of any local or systemic treatment. Peripheral blood of healthy volunteers and BM of patients with a nonmalignant breast lesion or a haematological malignancy served as the control group. Disseminated epithelial cells was detected by measuring relative gene expression (RGE) for cytokeratin-19 (CK-19) and mammaglobin (MAM), using a quantitative RT-PCR detection method. The mean follow-up time was 786 days (+/- 487). Kaplan-Meier analysis was used for predicting OS. By taking the 95 percentile of the RGE of CK-19 (BM: 26.3 and PB: 58.7) of the control group as cutoff, elevated CK-19 expression was detected in 42 (28%) BM samples and in 22 (15%) PB samples. Mammaglobin expression was elevated in 20% (both PB and BM) of the patients with BC. There was a 68% (CK-19) and 75% (MAM) concordance between PB and BM samples when classifying the results as either positive or negative. Patients with an elevated CK-19 or MAM expression in the BM had a worse prognosis than patients without elevated expression levels (OS: log-rank test, P=0.0045 (CK-19) and P=0.025 (MAM)). For PB survival analysis, no statistical significant difference was observed between patients with or without elevated CK-19 or MAM expression (OS: log-rank test, P=0.551 (CK-19) and P=0.329 (MAM)). Separate analyses of the M0 and M+ patients revealed a marked difference in OS according to the BM CK-19 or MAM status in the M+ patient group, but in the M0 group, only MAM expression was a prognostic marker for OS. Disseminated epithelial cells, measured as elevated CK-19 or MAM mRNA expression, could be detected in both PB and BM of patients with BC. Only the presence of DEC in BM was highly predictive for OS. The occurrence of DEC in the BM is probably less time-dependent and may act as a filter for circulating BC cells. The use of either larger volumes of PB or performing an enrichment step for circulating tumour in blood cells might improve these results.
In this paper we present estimates for the external costs of heavy-duty vehicles. The assessment of environmental impacts through air pollution is based on the ExternE methodology and it is part of a ...European wide project co-funded by the European Commission. It is based on a detailed 'impact-pathway analysis', which quantifies impacts on human health and the environment in 4 consecutive steps: specification of emissions, dispersion simulation, impact assessment with dose-response functions and monetary valuation. Until now, we have only assessed externalities of Belgian passenger cars with this methodology. This paper is the first in which our results for buses and lorries in Belgium are presented and discussed. Different types of vehicles and technologies are then compared while t
An analysis of physical planning at the township level in Belgium is undertaken on the basis of data for the period 1946-1970 for 1,445 townships. The effects of province & linguistic region, ...population size & area, population growth, population density, SES, economic activity, & political control of the township on the number of townships with particular plans & the number of plans in these townships are examined. Analysis is based on percentages & r coefficients. Area, population density, home ownership, education, commerce, & services affect the number of particular plans, with education, commerce & services, & population size being good predictors. 10 Tables. Modified HA.
We make publicly available a catalog of calibrated environmental measures for galaxies in the five 3D-Hubble Space Telescope (HST)/CANDELS deep fields. Leveraging the spectroscopic and grism ...redshifts from the 3D-HST survey, multiwavelength photometry from CANDELS, and wider field public data for edge corrections, we derive densities in fixed apertures to characterize the environment of galaxies brighter than mag in the redshift range . By linking observed galaxies to a mock sample, selected to reproduce the 3D-HST sample selection and redshift accuracy, each 3D-HST galaxy is assigned a probability density function of the host halo mass, and a probability that it is a central or a satellite galaxy. The same procedure is applied to a z = 0 sample selected from Sloan Digital Sky Survey. We compute the fraction of passive central and satellite galaxies as a function of stellar and halo mass, and redshift, and then derive the fraction of galaxies that were quenched by environment specific processes. Using the mock sample, we estimate that the timescale for satellite quenching is it is longer at lower stellar mass or lower redshift, but remarkably independent of halo mass. This indicates that, in the range of environments commonly found within the 3D-HST sample ( ), satellites are quenched by exhaustion of their gas reservoir in the absence of cosmological accretion. We find that the quenching times can be separated into a delay phase, during which satellite galaxies behave similarly to centrals at fixed stellar mass, and a phase where the star formation rate drops rapidly ( Gyr), as shown previously at z = 0. We conclude that this scenario requires satellite galaxies to retain a large reservoir of multi-phase gas upon accretion, even at high redshift, and that this gas sustains star formation for the long quenching times observed.
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