Summary
Variants of survivin with differing subcellular localizations might mediate the different functions of survivin, i.e. cell-cycle regulation and apoptosis inhibition. Highly proliferative tumors are more sensitive to chemotherapy, whereas apoptosis resistant cells would be refractory to endocrine therapy. Possibly, this explains incongruent data on the association of survivin with prognosis in breast cancer. Survivin levels were measured using ELISA in 800 × g pellets and 100,000 × g supernatants of breast cancer tissues from patients that were treated with either chemotherapy or endocrine therapy for advanced disease. These fractions might be enriched with nuclear or cytoplasmatic located survivin variants. Survivin levels were associated with tumors with poor prognostic clinical characteristics. For the patients treated with endocrine therapy, the patients with high survivin levels exhibited a significantly shorter progression free survival (PFS) than those who had low levels (pellet survivin Hazard Ratio (HR)=2.74, 95% Confidence Interval (CI)=1.31–5.72, p=0.008 and median PFS 5.8 versus 8.6 months, p=0.006, log-rank; cytosolic survivin HR=3.03, 95% CI=1.45–6.35, p=0.003). In contrast, for patients treated with chemotherapy, those with high cytosolic survivin had a significantly longer PFS than those with low levels (median PFS of 6.2 months, versus 4.7 months for patients with low cytosolic concentrations, p=0.024, log-rank). Thus, high levels of survivin are mainly related with a poor response to endocrine therapy, but a good response to chemotherapy. This phenomenon might be related to the different functions of survivin.
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Acknowledgements
The excellent technical assistance of Joop Heuvel and Anneke Geurts-Moespot of the Department of Chemical Endocrinology of the Radboud University Nijmegen Medical Center is gratefully acknowledged. We thank the contributors, especially the surgeons and internists, of the Radboud University Nijmegen Medical Centre and of the community hospitals in the region: Medical Centre Apeldoorn, Apeldoorn, Rijnstate Hospital, Arnhem, Maas Hospital, Boxmeer, Deventer Hospital, Deventer, Gelderse Vallei, Ede, Canisius-Wilhemina Hospital, Nijmegen, Streek-Hospital Zevenaar, Zevenaar, and Nieuw Spitaal, Zutphen, for their assistance in collecting the patients’ clinical follow-up data.
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Span, P.N., Tjan-Heijnen, V.C., Manders, P. et al. High survivin predicts a poor response to endocrine therapy, but a good response to chemotherapy in advanced breast cancer. Breast Cancer Res Treat 98, 223–230 (2006). https://doi.org/10.1007/s10549-005-9153-0
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DOI: https://doi.org/10.1007/s10549-005-9153-0