Prognostic Significance of BIRC5/Survivin in Breast Cancer: Results from Three Independent Cohorts

SIMPLE SUMMARY: Survivin, coded by the BIRC5 gene, is the cell death preventing protein, which is important for cell division in normal and cancer cells. It is intensively studied as a cancer biomarker and target for antitumor therapy. In this study we asked if we could get clinically helpful information on how active BIRC5 is in breast cancer patients? We studied the BIRC5 protein level in tumor samples for breast cancer patients from a West Swedish cohort and its mRNA level in two different public gene expression databases. Survival analysis demonstrated that a higher BIRC5 protein or mRNA level was associated with poor survival in all cohorts and for different cancer subtypes. We show that BIRC5 is a promising independent cancer survival marker. ABSTRACT: Breast cancer (BC) histological and molecular classifications significantly improved the treatment strategy and prognosis. Inhibitor of apoptosis BIRC5/survivin is often overexpressed in cancers, however, indications of its importance in BC are inconsistent. We integrate BIRC5 protein and mRNA measures with clinical associates and long-term outcome in three independent cohorts Protein levels of BIRC5 were measured in primary lysates of 845 patients of the West Swedish BC cohort (VGR-BC) and linked to 5- and 27-years survival. The results were externally validated in transcriptomic data from METABRIC and SCAN-B cohorts. Survival analysis showed that high levels of BIRC5 were consistently associated with a poor probability of 5-year overall survival. High BIRC5 in VGR-BC contributed negatively to the disease-specific survival at 5 and 27 years. Subsets with different status by ER (estrogen receptor) expression and presence of nodal metastasis supported independent association of high BIRC5 with poor prognosis in all cohorts. In METABRIC and SCAN-B cohorts, high levels of BIRC5 mRNA were associated with the basal-like and luminal B molecular BC subtypes and with increasing histologic grade. BIRC5 is a sensitive survival marker that acts independent of ER and nodal status, and its levels need to be considered when making treatment decisions.