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

Abstract

PURPOSE:

Sphingolipids play important roles in apoptosis and cell proliferation. Sphingosine kinase 1 (SphK1) expression has a prognostic impact in primary breast cancer, but its predictive value is currently unknown.

METHODS:

A total of 112 breast cancer specimens from a prospective neoadjuvant chemotherapy trial (GeparDuo) 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 to an immune reactive score of SphK1 was used as cutoff for high expression.

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; Fisher test p = 0.073). Eighteen of the 112 patients demonstrated a pathological complete response. A significant predictive value for pathological complete response was observed for ER negativity (p = 0.003), young age (p = 0.037), and high tumor grade (p = 0.049). An increased pCR rate was observed in tumors with high SphK1 expression within the luminal subtype (26.7 vs. 5.8 %; Fisher test p = 0.040). No significant difference in survival was detected according to SphK1 expression.

CONCLUSIONS:

Our results suggest that SphK1 may be a predictive factor for pCR after neoadjuvant treatment in luminal type breast cancers and warrants further investigation.

• Authors: Eugen Ruckhäberle, Thomas Karn, Carsten Denkert, Sibylle Loibl, Beyhan Ataseven, Toralf Reimer, Sven Becker, Uwe Holtrich, Achim Rody, Silvia Darb-Esfahani, Valentina Nekljudova, Gunter von Minckwitz
• Journal: Journal of cancer research and clinical oncology (J Cancer Res Clin Oncol) Vol. 139 Issue 10 Pg. 1681-9 (Oct 2013) ISSN: 1432-1335 [Electronic] Germany
• PMID: 23955546 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptors, Estrogen
• Phosphotransferases (Alcohol Group Acceptor)
• sphingosine kinase
• ERBB2 protein, human
• Receptor, ErbB-2

Topics

• Breast Neoplasms (drug therapy, enzymology, mortality)
• Chemotherapy, Adjuvant
• Disease-Free Survival
• Female
• Humans
• Kaplan-Meier Estimate
• Middle Aged
• Neoadjuvant Therapy
• Phosphotransferases (Alcohol Group Acceptor)
• Proportional Hazards Models
• Randomized Controlled Trials as Topic
• Receptor, ErbB-2 (metabolism)
• Receptors, Estrogen (metabolism)
• Treatment Outcome