Predictive value of sphingosine kinase-1 expression in neoadjuvant treatment of breast cancer.

Abstract

615 Background: Sphingolipids play important roles in apoptosis, senescence, cell proliferation and angiogenesis. Spingosine kinase 1 (SphK1) expression was shown to have prognostic impact in primary breast cancer. However, the predictive value of SpHK1 in neoadjuvant treatment of breast cancer is currently unknown. Methods: A total of 112 breast cancer specimen from a prospective neoadjuvant chemotherapy trial (GeparDuo, 4x AC-Doc vs. 4x ADoc) were studied. Using tissue microarrays of pre-treatment core cut biopsies we determined the expression of SphK1 by immunohistochemistry. The upper quartile of the cohort according an immune reactive score of Sphk1 was used as cutoff for high expression. Fisher's Exact Test was used for cross tabulation. The predictive value of SphK1 expression for a pathological complete response (pCR) was analyzed using logistic regression. Impact of SphK1 on survival was analyzed by the Kaplan Meier method using follow up data from the clinical trial. Results: We observed a larger number of samples with high SphK1 expression among ER negative cancers (36.8% vs. 20.5% among ER positive cancers; p=0.073). Eighteen of the 112 patients demonstrated a pathological complete response. Hormone receptor status (p<0.001), age under 40 years (P=0.030), and tumor grade (P=0.049) were significant factors for a pCR. A trend for an increased pCR rate was observed in tumors with high SphK1 expression, especially in the luminal A subtype (27.3 vs. 5.6%; p=0.076). When analyzing the follow up information of the patients no significant difference in survival was detected between patients with high or low SphK1 expression. Conclusions: Our preliminary results suggest that SphK1 could be a predictive factor for higher pCR rates in neoadjuvant treatment of breast cancer and warrants further investigation.