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Survivin Is an Independent Prognostic Marker for Risk Stratification of Breast Cancer Patients

Departments of¹ Chemical Endocrinology, ² Clinical Chemistry, and ³ Medical Oncology, University Medical Center Nijmegen, Nijmegen, The Netherlands.

^aAddress correspondence to this author at: 530 Department of Chemical Endocrinology, University Medical Center Nijmegen, PO Box 9101, 6500 HB Nijmegen, The Netherlands. Fax 31-24-3541484; e-mail p.span{at}ace.umcn.nl.

Background: Results in previous qualitative studies of the association of the apoptosis inhibitor survivin with prognosis of breast cancer patients have been contradictory.

Methods: Survivin mRNA was measured by quantitative TaqMan reverse transcription-PCR in 275 breast cancer tissues from patients with operable tumors and was correlated with established clinicopathologic factors, relapse-free survival [(RFS); 102 events], and overall survival [(OS); 81 events].

Results: High survivin mRNA concentrations were found mainly in tissues from younger patients and in high-grade cancer tissues. High survivin concentrations were most strongly associated with estrogen receptor- or progesterone receptor-negative tumors. In univariate Cox regression analysis for RFS, survivin concentrations were significantly associated with poor prognosis with a hazard ratio (HR) of 1.99 (95% confidence interval, 1.31–3.02; P = 0.001) for every 10-fold increase in expression. For OS, a significant contribution of survivin to poor prognosis was found with a HR of 2.76 (1.67–4.55; P <0.001). Multivariate analyses were performed including established clinicopathologic factors. For RFS, age (P = 0.027), nodal category (P <0.001), and survivin [HR = 1.78 (1.18–2.68); P = 0.006] contributed significantly to the model. For OS, only nodal category (P <0.001) and survivin [HR = 3.05 (1.83–5.10); P <0.001] were significant.

Conclusion: Survivin demonstrates a strong, independent, association with poor prognosis. Survivin might be used as a new marker to stratify breast cancer patients for more optimal treatment modalities, or it could be a promising new target for therapy.

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