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Establishment and validation of circulating tumor cell-based prognostic nomograms in first-line metastatic breast cancer patients.

ABSTRACT: Circulating tumor cells (CTC) represent a new outcome-associated biomarker independent from known prognostic factors in metastatic breast cancer (MBC). The objective here was to develop and validate nomograms that combined baseline CTC counts and the other prognostic factors to assess the outcome of individual patients starting first-line treatment for MBC.We used a training set of 236 patients with MBCs starting a first-line treatment from the M.D. Anderson Cancer Center (Houston, TX) to establish nomograms that calculated the predicted probability of survival at different time points: 1, 2, and 5 years for overall survival (OS) and 6 months and 1 and 2 years for progression-free survival (PFS).The covariates computed in the model were age, disease subtype, visceral metastases, performance status, and CTC counts by CellSearch. Nomograms were independently validated with 210 patients with MBCs from the Institut Curie (Paris, France) who underwent first-line chemotherapy. The discriminatory ability and accuracy of the models were assessed using Harrell c-statistic and calibration plots at different time points in both training and validation datasets.Median follow-up was of 23 and 29 months in the MD Anderson and Institut Curie cohorts, respectively. Nomograms showed good c-statistics: 0.74 for OS and 0.65 for PFS and discriminated OS prediction at 1, 2, and 5 years, and PFS prediction at 6 months and 1 and 2 years.Nomograms, which relied on CTC counts as a continuous covariate, easily facilitated the use of a web-based tool for estimating survival, supporting treatment decisions and clinical trial stratification in first-line MBCs.

SUBMITTER: Giordano A

PROVIDER: S-EPMC3662240 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Establishment and validation of circulating tumor cell-based prognostic nomograms in first-line metastatic breast cancer patients.

Giordano Antonio A Egleston Brian L BL Hajage David D Bland Joseph J Hortobagyi Gabriel N GN Reuben James M JM Pierga Jean-Yves JY Cristofanilli Massimo M Bidard Francois-Clement FC

Clinical cancer research : an official journal of the American Association for Cancer Research 20130122 6

<h4>Purpose</h4>Circulating tumor cells (CTC) represent a new outcome-associated biomarker independent from known prognostic factors in metastatic breast cancer (MBC). The objective here was to develop and validate nomograms that combined baseline CTC counts and the other prognostic factors to assess the outcome of individual patients starting first-line treatment for MBC.<h4>Experimental design</h4>We used a training set of 236 patients with MBCs starting a first-line treatment from the M.D. An ...[more]

PMID: 23340302

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Project description:BACKGROUND:Epithelial-mesenchymal transition (EMT) is implicated in the metastatic process and presents a challenge to epithelial cell adhesion molecule-based detection of circulating tumor cells (CTCs), which have been demonstrated to be a prognostic indicator in metastatic breast cancer. Although evidence has indicated that heterogeneity of CTCs based on EMT markers is associated with disease progression, no standard recommendations have been established for clinical practice. This study aimed to evaluate the prognostic significance of dynamic CTC detection based on EMT for metastatic breast cancer patients. METHODS:We enrolled 108 human epidermal growth factor receptor 2-negative metastatic breast cancer patients from the prospective phase III CAMELLIA study and applied the CanPatrol CTC enrichment technique to identify CTC phenotypes (including epithelial CTCs, biphenotypic epithelial/mesenchymal CTCs, and mesenchymal CTCs) in peripheral blood samples. Receiver operating characteristic curve analyses of total CTC count and the proportion of mesenchymal CTCs for predicting the 1-year progression-free survival (PFS) rate were conducted to determine the optimal cut-off values, and Kaplan-Meier analysis and Cox proportional hazards regression analysis were performed to investigate the prognostic value of the cut-off values of both total CTC count and the proportion of mesenchymal CTCs in combination. RESULTS:For predicting the 1-year PFS rate, the optimal cut-off value of total CTC count was 9.5 (Area under the curve [AUC]?=?0.538, 95% confidence interval [CI]?=?0.418-0.657), and that of the proportion of mesenchymal CTCs was 10.7% (AUC?=?0.581, 95% CI?=?0.463-0.699). We used the two cut-off values in combination to forecast PFS in which the total CTC count was equaled to or exceeded 10/5 mL with the proportion of mesenchymal CTCs surpassed 10.7%. Patients who met the combined criteria had significantly shorter median PFS than did those who did not meet the criteria (6.2 vs. 9.9 months, P?=0.010). A nomogram was constructed based on the criteria and significant clinicopathological characteristics with a C-index of 0.613 (P?=?0.010). CONCLUSIONS:The criteria, which combine the total CTC count and the proportion of mesenchymal CTCs, may be used to monitor therapeutic resistance and predict prognosis in patients with metastatic breast cancer. Trial registration ClinicalTrials.gov. NCT01917279. Registered on 19 July 2013, https://clinicaltrials.gov/ct2/show/NCT01917279?term=NCT01917279&rank=1 .

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Dataset Information

Establishment and validation of circulating tumor cell-based prognostic nomograms in first-line metastatic breast cancer patients.

Publications

Establishment and validation of circulating tumor cell-based prognostic nomograms in first-line metastatic breast cancer patients.

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