Alessandra Gennari1, Flavia Foca2, Rita Zamarchi3, Andrea Rocca4, Dino Amadori4, Andrea De Censi5, Alessandra Bologna6, Luigi Cavanna7, Lorenzo Gianni8, Laura Scaltriti9, Elisabetta Rossi3,10, Antonella Facchinetti3,10, Veronica Martini11, Paolo Bruzzi12, Oriana Nanni2. 1. Medical Oncology, Department of Translational Medicine, University of Eastern Piedmont, Via Solaroli 17, 28100, Novara, Italy. alessandra.gennari@uniupo.it. 2. Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 3. Department of Immunology and Oncological Molecular Diagnostics, Veneto Institute of Oncology (IOV) IRCCS, Padua, Italy. 4. Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy. 5. Division of Medical Oncology, EO Ospedali Galliera, Genoa, Italy. 6. Department of Oncology, Arcispedale S. Maria Nuova IRCCS, Reggio Emilia, Italy. 7. Oncology-Hematology Department, Hospital of Piacenza, Piacenza, Italy. 8. Department of Medical Oncology, Ospedale Infermi, Rimini, Italy. 9. Oncology Day Hospital Unit, Ospedale Civile Di Guastalla, Guastalla, Italy. 10. Department of Surgery, Oncology and Gastroenterology, University of Paduva, Paduva, Italy. 11. Medical Oncology, Department of Translational Medicine, University of Eastern Piedmont, Via Solaroli 17, 28100, Novara, Italy. 12. Department of Clinical Epidemiology, IRCCS San Martino - IST, Genoa, Italy.
Abstract
PURPOSE: To evaluate the prognostic value of IGF-1R expression on circulating tumor cells (CTCs) in a prospective randomized clinical trial comparing chemotherapy plus metformin with chemotherapy alone in metastatic breast cancer (MBC) patients. METHODS: CTCs were collected at baseline and at the end of chemotherapy. An automated sample preparation and analysis system (CellSearch) were customized for detecting IGF-1R expression. The prognostic role of CTC count and IGF-1R was assessed for PFS and OS by univariate and multivariate analyses. RESULTS:Seventy-two out of 126 randomized patients were evaluated: 57% had ≥ 1 IGF-1R positive CTC and 37.5% ≥ 4 IGF-1R negative cells; 42% had CTC count ≥ 5/7.5 ml. At univariate analysis, the number of IGF-1R negative CTCs was strongly associated with risk of progression and death: HR 1.93 (P = 0.013) and 3.65 (P = 0.001), respectively; no association was detected between number of IGF-1R positive CTCs and PFS or OS (P = 0.322 and P = 0.840). The prognostic role of CTC count was confirmed: HR 1.69, P = 0.042 for PFS and HR 2.80 for OS, P = 0.002. By multivariate analysis, the prognostic role of the number of IGF-1R negative CTCs was maintained, while no residual prognostic role of CTC count or number of IGF-1R positive cells was found. CONCLUSION: Loss of IGF-1R in CTCs is associated with a significantly worse outcome in MBC patients. This finding supports further evaluation for the role of IGF-1R on CTCs to improve patient stratification and to implement new targeted strategies. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov (NCT01885013); European Clinical Trials Database (EudraCT No.2009-014,662-26).
RCT Entities:
PURPOSE: To evaluate the prognostic value of IGF-1R expression on circulating tumor cells (CTCs) in a prospective randomized clinical trial comparing chemotherapy plus metformin with chemotherapy alone in metastatic breast cancer (MBC) patients. METHODS: CTCs were collected at baseline and at the end of chemotherapy. An automated sample preparation and analysis system (CellSearch) were customized for detecting IGF-1R expression. The prognostic role of CTC count and IGF-1R was assessed for PFS and OS by univariate and multivariate analyses. RESULTS: Seventy-two out of 126 randomized patients were evaluated: 57% had ≥ 1 IGF-1R positive CTC and 37.5% ≥ 4 IGF-1R negative cells; 42% had CTC count ≥ 5/7.5 ml. At univariate analysis, the number of IGF-1R negative CTCs was strongly associated with risk of progression and death: HR 1.93 (P = 0.013) and 3.65 (P = 0.001), respectively; no association was detected between number of IGF-1R positive CTCs and PFS or OS (P = 0.322 and P = 0.840). The prognostic role of CTC count was confirmed: HR 1.69, P = 0.042 for PFS and HR 2.80 for OS, P = 0.002. By multivariate analysis, the prognostic role of the number of IGF-1R negative CTCs was maintained, while no residual prognostic role of CTC count or number of IGF-1R positive cells was found. CONCLUSION: Loss of IGF-1R in CTCs is associated with a significantly worse outcome in MBC patients. This finding supports further evaluation for the role of IGF-1R on CTCs to improve patient stratification and to implement new targeted strategies. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov (NCT01885013); European Clinical Trials Database (EudraCT No.2009-014,662-26).
Entities:
Keywords:
Breast cancer (BC); Circulating tumor cells (CTCs); Clinical trials; Invasion; Liquid biopsy; Metastasis
Authors: Daniel F Hayes; Massimo Cristofanilli; G Thomas Budd; Matthew J Ellis; Alison Stopeck; M Craig Miller; Jeri Matera; W Jeffrey Allard; Gerald V Doyle; Leon W W M Terstappen Journal: Clin Cancer Res Date: 2006-07-15 Impact factor: 12.531
Authors: Massimo Cristofanilli; G Thomas Budd; Matthew J Ellis; Alison Stopeck; Jeri Matera; M Craig Miller; James M Reuben; Gerald V Doyle; W Jeffrey Allard; Leon W M M Terstappen; Daniel F Hayes Journal: N Engl J Med Date: 2004-08-19 Impact factor: 91.245
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