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

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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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Acknowledgements

We acknowledge the contributions of Dr. Jozien Helleman, drs. Marion E. Meijer-van Gelder and Roya Sarwari. This research was supported, in part, by grants of the Association for International Cancer Research, the Susan G. Komen Breast Cancer Foundation, the Dutch Cancer Society, and the “Breedte-strategie” of the Erasmus MC.

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Authors and Affiliations

  1. Department of Pathology, Josephine Nefkens Institute, Erasmus MC, Room Be 432, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands

    Danielle Meijer, Ton van Agthoven & Lambert C. J. Dorssers

  2. Department of Medical Oncology, Josephine Nefkens Institute, Erasmus MC, Rotterdam, The Netherlands

    Maurice P. H. M. Jansen, Maxime P. Look, Kirsten Ruigrok-Ritstier, Iris L. van Staveren, Anieta M. Sieuwerts, John A. Foekens & Els M. J. J. Berns

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  1. Danielle Meijer
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  2. Maurice P. H. M. Jansen
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  3. Maxime P. Look
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  5. Iris L. van Staveren
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  9. Lambert C. J. Dorssers
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Correspondence to Lambert C. J. Dorssers.

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Danielle Meijer and Maurice P.H.M. Jansen contributed equally to this work.

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Meijer, D., Jansen, M.P.H.M., Look, M.P. et al. TSC22D1 and PSAP predict clinical outcome of tamoxifen treatment in patients with recurrent breast cancer. Breast Cancer Res Treat 113, 253–260 (2009). https://doi.org/10.1007/s10549-008-9934-3

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  • DOI: https://doi.org/10.1007/s10549-008-9934-3

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