title: Predictive value of sphingosine kinase 1 expression in neoadjuvant treatment of breast cancer.
abstract: OBJECTIVE
  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: Department of Obstetrics and Gynecology, Goethe University Frankfurt, Theodor-Stern Kai 7, 60590, Frankfurter, Germany.
authors: Eugen
authors: E
authors: Ruckhäberle
authors: Thomas
authors: T
authors: Karn
authors: Carsten
authors: C
authors: Denkert
authors: Sibylle
authors: S
authors: Loibl
authors: Beyhan
authors: B
authors: Ataseven
authors: Toralf
authors: T
authors: Reimer
authors: Sven
authors: S
authors: Becker
authors: Uwe
authors: U
authors: Holtrich
authors: Achim
authors: A
authors: Rody
authors: Silvia
authors: S
authors: Darb-Esfahani
authors: Valentina
authors: V
authors: Nekljudova
authors: Gunter
authors: G
authors: von Minckwitz
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000401:mortality; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D017853:Phosphotransferases (Alcohol Group Acceptor); D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D016896:Treatment Outcome; D000099157:Sphingosine Kinase
chemical_list: D017853:Phosphotransferases (Alcohol Group Acceptor); D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D000099157:Sphingosine Kinase; C508053:ERBB2 protein, human
references: Mol Endocrinol. 2003 Oct;17(10):2002-12
references: 12881510
references: Cancer Metastasis Rev. 2011 Dec;30(3-4):567-76
references: 22005951
references: Br J Cancer. 2012 Apr 10;106(8):1453-9
references: 22460268
references: Am J Pathol. 2010 Nov;177(5):2205-15
references: 20889557
references: J Clin Oncol. 2012 May 20;30(15):1796-804
references: 22508812
references: Int J Cancer. 2013 Feb 1;132(3):605-16
references: 22733311
references: J Mol Endocrinol. 2011 Apr 28;46(3):205-16
references: 21321095
references: Steroids. 2009 Jul;74(7):562-7
references: 19167412
references: J Clin Oncol. 2005 Apr 20;23(12):2676-85
references: 15837982
references: Nat Rev Cancer. 2004 Aug;4(8):604-16
references: 15286740
references: Int J Hematol. 2008 Apr;87(3):266-75
references: 18283525
references: Cancer. 2011 Apr 15;117(8):1575-82
references: 21472705
references: Histopathology. 1991 Nov;19(5):403-10
references: 1757079
references: Future Oncol. 2010 Oct;6(10):1603-24
references: 21062159
references: Exp Biol Med (Maywood). 2012 Jul;237(7):832-44
references: 22859737
references: Breast Cancer Res. 2009;11(5):R69
references: 19758440
references: Int J Cancer. 2009 Dec 1;125(11):2728-36
references: 19521959
references: J Pathol. 2012 Feb;226(3):482-94
references: 21953249
references: Breast Cancer Res Treat. 2008 Nov;112(1):41-52
references: 18058224
references: Breast. 2007 Jun;16(3):235-40
references: 17449250
references: Lancet Oncol. 2010 Apr;11(4):358-65
references: 20189874
references: J Cell Biol. 2006 Apr 24;173(2):301-10
references: 16636149
references: J Clin Oncol. 2005 Dec 20;23(36):9067-72
references: 16172462
references: J Leukoc Biol. 1999 Mar;65(3):341-4
references: 10080537
references: Nat Chem Biol. 2010 Jul;6(7):489-97
references: 20559316
references: Exp Biol Med (Maywood). 2009 Nov;234(11):1253-63
references: 19546354
references: Ann Surg Oncol. 2012 May;19(5):1508-16
references: 22193884
references: Ann Oncol. 2011 Aug;22(8):1736-47
references: 21709140
references: Endocrinology. 2009 Oct;150(10):4484-92
references: 19706837
references: Clin Cancer Res. 2005 Aug 15;11(16):5678-85
references: 16115903
references: J Biol Chem. 2010 Apr 2;285(14):10477-86
references: 20110355
references: J Clin Epidemiol. 2010 Aug;63(8):834-40
references: 20346629
references: J Surg Oncol. 2011 Mar 15;103(4):348-57
references: 21337570
references: J Natl Cancer Inst. 2011 Feb 02;103(3):264-72
references: 21191116
references: Mol Cell Biol. 2010 Aug;30(15):3827-41
references: 20516217
references: FEBS Lett. 2005 Oct 10;579(24):5313-7
references: 16194537
references: Biochim Biophys Acta. 2006 Dec;1758(12):2016-26
references: 16996023