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01-10-2010 | Preclinical study

Nuclear IRS-1 predicts tamoxifen response in patients with early breast cancer

Authors: Ilenia Migliaccio, Meng-Fen Wu, Carolina Gutierrez, Luca Malorni, Syed K. Mohsin, D. Craig Allred, Susan G. Hilsenbeck, C. Kent Osborne, Heidi Weiss, Adrian V. Lee

Published in: Breast Cancer Research and Treatment | Issue 3/2010

Abstract

Insulin receptor substrate-1 (IRS-1) is a cytoplasmic scaffolding protein that is phosphorylated by insulin-like growth factor-I receptor and recruits downstream effectors. Recent evidence suggests that IRS-1 has a nuclear localization and function. Here we investigated whether nuclear and cytoplasmic IRS-1 levels are associated with clinico-pathological characteristics and clinical outcome in breast cancer patients. Tissue microarrays from 1,097 patients with stage I–II breast cancer were stained by immunohistochemistry for IRS-1. Nuclear and cytoplasmic IRS-1 were scored separately according to the Allred score. Nuclear IRS-1 showed a positive association with estrogen receptor (ER) (r = 0.09, P = 0.003) and progesterone receptor (PR) (r = 0.08, P = 0.008) status and a negative correlation with lymph node involvement (r = −0.10, P = 0.001). Cytoplasmic IRS-1 did not correlate with ER or PR but showed a positive correlation with tumor size (r = 0.10, P = 0.001) and S-phase fraction (r = 0.16, P < 0.001). In univariate analysis, tamoxifen-treated patients with tumors showing positive nuclear IRS-1 had a better recurrence-free survival (RFS) (P = 0.009) and overall survival (OS) (P = 0.0007), while no association was shown between cytoplasmic IRS-1 and RFS or OS in the same group of patients. In multivariate analysis of patients receiving tamoxifen, negative nuclear IRS-1 showed a significantly reduced RFS (P = 0.046) and OS (P = 0.018). Combining both PR and nuclear IRS-1, tamoxifen-treated patients with PR+/IRS-1+ tumors had a better RFS (P = 0.0003) and OS (P < 0.0001) when compared with patients with PR−/IRS-1− tumors. In conclusion, nuclear IRS-1 may be a useful marker to predict tamoxifen response in patients with early breast cancer, particularly when assessed in combination with PR.

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Title: Nuclear IRS-1 predicts tamoxifen response in patients with early breast cancer
Authors: Ilenia Migliaccio
Meng-Fen Wu
Carolina Gutierrez
Luca Malorni
Syed K. Mohsin
D. Craig Allred
Susan G. Hilsenbeck
C. Kent Osborne
Heidi Weiss
Adrian V. Lee
Publication date: 01-10-2010
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 3/2010
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-009-0632-6

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