The clinical use of circulating tumor cells (CTCs) enumeration for staging of metastatic breast cancer (MBC): International expert consensus paper

BACKGROUND: The heterogeneity of metastatic breast cancer (MBC) necessitates novel biomarkers allowing stratification of patients for treatment selection and drug development. We propose to use the prognostic utility of circulating tumor cells (CTCs) for stratification of patients with stage IV disease. METHODS: In a retrospective, pooled analysis of individual patient data from 18 cohorts, including 2436 MBC patients, a CTC threshold of 5 cells per 7.5\u2009ml was used for stratification based on molecular subtypes, disease location, and prior treatments. Patients with 65 5 CTCs were classified as Stage IVaggressive, those with < 5 CTCs as Stage IVindolent. Survival was analyzed using Kaplan-Meier curves and the log rank test. RESULTS: For all patients, Stage IVindolent patients had longer median overall survival than those with Stage IVaggressive (36.3 months vs. 16.0 months, P\u2009<\u20090.0001) and similarly for de novo MBC patients (41.4 months Stage IVindolent vs. 18.7 months Stage IVaggressive, p\u2009<\u20090.0001). Moreover, patients with Stage IVindolent disease had significantly longer overall survival across all disease subtypes compared to the aggressive cohort: hormone receptor-positive (44 months vs. 17.3 months, P\u2009<\u20090.0001), HER2-positive (36.7 months vs. 20.4 months, P\u2009<\u20090.0001), and triple negative (23.8 months vs. 9.0 months, P\u2009<\u20090.0001). Similar results were obtained regardless of prior treatment or disease location. CONCLUSIONS: We confirm the identification of two subgroups of MBC, Stage IVindolent and Stage IVaggressive, independent of clinical and molecular variables. Thus, CTC count should be considered an important tool for staging of advanced disease and for disease stratification in prospective clinical trials

Articles Clinical validity of circulating tumour cells in patients with metastatic breast cancer: a pooled analysis of individual patient data

Summary Background We aimed to assess the clinical validity of circulating tumour cell (CTC) quantifi cation for prognostication of patients with metastatic breast cancer by undertaking a pooled analysis of individual patient data

The clinical use of circulating tumor cells (CTCs) enumeration for staging of metastatic breast cancer (MBC): International expert consensus paper.

The heterogeneity of metastatic breast cancer (MBC) necessitates novel biomarkers allowing stratification of patients for treatment selection and drug development. We propose to use the prognostic utility of circulating tumor cells (CTCs) for stratification of patients with stage IV disease.SCOPUS: re.jinfo:eu-repo/semantics/publishe

Clinical validity of circulating tumour cells in patients with metastatic breast cancer: A pooled analysis of individual patient data

BACKGROUND: We aimed to assess the clinical validity of circulating tumour cell (CTC) quantification for prognostication of patients with metastatic breast cancer by undertaking a pooled analysis of individual patient data. METHODS: We contacted 51 European centres and asked them to provide reported and unreported anonymised data for individual patients with metastatic breast cancer who participated in studies between January, 2003, and July, 2012. Eligible studies had participants starting a new line of therapy, data for progression-free survival or overall survival, or both, and CTC quantification by the CellSearch method at baseline (before start of new treatment). We used Cox regression models, stratified by study, to establish the association between CTC count and progression-free survival and overall survival. We used the landmark method to assess the prognostic value of CTC and serum marker changes during treatment. We assessed the added value of CTCs or serum markers to prognostic clinicopathological models in a resampling procedure using likelihood ratio (LR) \u3c7(2) statistics. FINDINGS: 17 centres provided data for 1944 eligible patients from 20 studies. 911 patients (46\ub79%) had a CTC count of 5 per 7\ub75 mL or higher at baseline, which was associated with decreased progression-free survival (hazard ratio [HR] 1\ub792, 95% CI 1\ub773-2\ub714, p<0\ub70001) and overall survival (HR 2\ub778, 95% CI 2\ub742-3\ub719, p<0\ub70001) compared with patients with a CTC count of less than 5 per 7\ub75 mL at baseline. Increased CTC counts 3-5 weeks after start of treatment, adjusted for CTC count at baseline, were associated with shortened progression-free survival (HR 1\ub785, 95% CI 1\ub748-2\ub732, p<0\ub70001) and overall survival (HR 2\ub726, 95% CI 1\ub768-3\ub703) as were increased CTC counts after 6-8 weeks (progression-free survival HR 2\ub720, 95% CI 1\ub766-2\ub790, p<0\ub70001; overall survival HR 2\ub791, 95% CI 2\ub701-4\ub723, p<0\ub70001). Survival prediction was significantly improved by addition of baseline CTC count to the clinicopathological models (progression-free survival LR 38\ub74, 95% CI 21\ub79-60\ub73, p<0\ub70001; overall survival LR 64\ub79, 95% CI 41\ub73-93\ub74, p<0\ub70001). This model was further improved by addition of CTC change at 3-5 weeks (progression-free survival LR 8\ub72, 95% CI 0\ub778-20\ub74, p=0\ub7004; overall survival LR 11\ub75, 95% CI 2\ub76-25\ub71, p=0\ub70007) and at 6-8 weeks (progression-free survival LR 15\ub73, 95% CI 5\ub72-28\ub73; overall survival LR 14\ub76, 95% CI 4\ub70-30\ub76; both p<0\ub70001). Carcinoembryonic antigen and cancer antigen 15-3 concentrations at baseline and during therapy did not add significant information to the best baseline model. INTERPRETATION: These data confirm the independent prognostic effect of CTC count on progression-free survival and overall survival. CTC count also improves the prognostication of metastatic breast cancer when added to full clinicopathological predictive models, whereas serum tumour markers do not