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01-01-2009 | Preclinical Study

TSC22D1 and PSAP predict clinical outcome of tamoxifen treatment in patients with recurrent breast cancer

Authors: Danielle Meijer, Maurice P. H. M. Jansen, Maxime P. Look, Kirsten Ruigrok-Ritstier, Iris L. van Staveren, Anieta M. Sieuwerts, Ton van Agthoven, John A. Foekens, Lambert C. J. Dorssers, Els M. J. J. Berns

Published in: Breast Cancer Research and Treatment | Issue 2/2009

Abstract

Purpose Two genes, TSC22 domain family, member 1 (TSC22D1) and prosaposin (PSAP) were identified in an in vitro functional screen for genes having a causative role in tamoxifen resistance. These genes were also present in our previously established 81-gene signature for resistance to first-line tamoxifen therapy. The aim of this study was to investigate the predictive value of these genes for tamoxifen therapy failure in patients with recurrent breast cancer. Experimental Design The mRNA levels of TSC22D1 and PSAP were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in 223 estrogen receptor-positive primary breast tumors of patients with recurrent disease treated with first-line tamoxifen therapy. The main objective of this study was the length of progression-free survival (PFS). Results High mRNA levels of TSC22D1 and PSAP were significantly associated with shorter PFS and both were independent of the traditional predictive factors (HR = 1.30, 95% CI = 1.04–1.64 P = 0.023; and HR = 1.40, 95% CI = 1.03–1.88, P = 0.029, respectively). In multivariate analysis, patients with high mRNA levels of both genes associated significantly with no clinical benefit (OR = 0.19, 95% CI = 0.06–0.62, P = 0.006) and had the shortest PFS (HR = 2.05, 95% CI = 1.29–3.25, P = 0.002). Conclusion These results confirm our previous in vitro and tumor-related findings and are indicative for the failure of tamoxifen treatment in breast-cancer patients. Both TSC22D1 and PSAP are associated with clinical outcome and may have a functional role in therapy resistance.

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Title: TSC22D1 and PSAP predict clinical outcome of tamoxifen treatment in patients with recurrent breast cancer
Authors: Danielle Meijer
Maurice P. H. M. Jansen
Maxime P. Look
Kirsten Ruigrok-Ritstier
Iris L. van Staveren
Anieta M. Sieuwerts
Ton van Agthoven
John A. Foekens
Lambert C. J. Dorssers
Els M. J. J. Berns
Publication date: 01-01-2009
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 2/2009
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-008-9934-3

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