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01-05-2020 | Breast Cancer | Clinical trial

Insulin-like growth factor-1 receptor (IGF-1R) expression on circulating tumor cells (CTCs) and metastatic breast cancer outcome: results from the TransMYME trial

Authors: Alessandra Gennari, Flavia Foca, Rita Zamarchi, Andrea Rocca, Dino Amadori, Andrea De Censi, Alessandra Bologna, Luigi Cavanna, Lorenzo Gianni, Laura Scaltriti, Elisabetta Rossi, Antonella Facchinetti, Veronica Martini, Paolo Bruzzi, Oriana Nanni

Published in: Breast Cancer Research and Treatment | Issue 1/2020

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).

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Title: Insulin-like growth factor-1 receptor (IGF-1R) expression on circulating tumor cells (CTCs) and metastatic breast cancer outcome: results from the TransMYME trial
Authors: Alessandra Gennari
Flavia Foca
Rita Zamarchi
Andrea Rocca
Dino Amadori
Andrea De Censi
Alessandra Bologna
Luigi Cavanna
Lorenzo Gianni
Laura Scaltriti
Elisabetta Rossi
Antonella Facchinetti
Veronica Martini
Paolo Bruzzi
Oriana Nanni
Publication date: 01-05-2020
Publisher: Springer US
Keywords: Breast Cancer
Insulins
Metformin
Breast Cancer
Insulins
Cytostatic Therapy
Published in: Breast Cancer Research and Treatment / Issue 1/2020
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-020-05596-4

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