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Insulin-like growth factor-1 receptor (IGF-1R) expression on circulating tumor cells (CTCs) and metastatic breast cancer outcome: results from the TransMYME trial
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Insulin-like growth factor-1 receptor (IGF-1R) expression on circulating tumor cells (CTCs) and metastatic breast cancer outcome: results from the TransMYME trial
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Journal Article
Insulin-like growth factor-1 receptor (IGF-1R) expression on circulating tumor cells (CTCs) and metastatic breast cancer outcome: results from the TransMYME trial
2020
Overview
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).
Publisher
Springer US,Springer Nature B.V
Subject
/ Antineoplastic Combined Chemotherapy Protocols - therapeutic use
/ Biomarkers, Tumor - metabolism
/ Breast Neoplasms - drug therapy
/ Breast Neoplasms - pathology
/ Clinical Trials, Phase II as Topic
/ Female
/ Humans
/ Insulin
/ Insulin-like growth factor I
/ Medicine
/ Neoplastic Cells, Circulating - metabolism
/ Neoplastic Cells, Circulating - pathology
/ Oncology
/ Randomized Controlled Trials as Topic
