title: Tryptophan degradation in women with breast cancer: a pilot study.
abstract: BACKGROUND
  Altered tryptophan metabolism and indoleamine 2,3-dioxygenase activity are linked to cancer development and progression. In addition, these biological factors have been associated with the development and severity of neuropsychiatric syndromes, including major depressive disorder. However, this biological mechanism associated with both poor disease outcomes and adverse neuropsychiatric symptoms has received little attention in women with breast cancer. Therefore, a pilot study was undertaken to compare levels of tryptophan and other proteins involved in tryptophan degradation in women with breast cancer to women without cancer, and secondarily, to examine levels in women with breast caner over the course of chemotherapy.
  
  
  RESULTS
  Blood samples were collected from women with a recent diagnosis of breast cancer (n = 33) before their first cycle of chemotherapy and after their last cycle of chemotherapy. The comparison group (n = 24) provided a blood sample prior to breast biopsy. Plasma concentrations of tryptophan, kynurenine, and tyrosine were determined. The kynurenine to tryptophan ratio (KYN/TRP) was used to estimate indoleamine 2,3-dioxygenase activity. On average, the women with breast cancer had lower levels of tryptophan, elevated levels of kynurenine and tyrosine and an increased KYN/TRP ratio compared to women without breast cancer. There was a statistically significant difference between the two groups in the KYN/TRP ratio (p = 0.036), which remained elevated in women with breast cancer throughout the treatment trajectory.
  
  
  CONCLUSIONS
  The findings of this pilot study suggest that increased tryptophan degradation may occur in women with early-stage breast cancer. Given the multifactorial consequences of increased tryptophan degradation in cancer outcomes and neuropsychiatric symptom manifestation, this biological mechanism deserves broader attention in women with breast cancer.
authors: Department of Family and Community Health Nursing, Virginia Commonwealth University School of Nursing, 1100 East Leigh Street, Richmond, Virginia, 23298, USA. delyon@vcu.edu.
authors: Debra E
authors: DE
authors: Lyon
authors: Jeanne M
authors: JM
authors: Walter
authors: Angela R
authors: AR
authors: Starkweather
authors: Christine M
authors: CM
authors: Schubert
authors: Nancy L
authors: NL
authors: McCain
references: Lung Cancer. 2010 Mar;67(3):361-5
references: 19487045
references: Mol Cancer Ther. 2008 Dec;7(12):3859-66
references: 19074858
references: Clin Cancer Res. 2006 Feb 15;12(4):1144-51
references: 16489067
references: Neuropsychopharmacology. 2001 Feb;24(2):130-40
references: 11120395
references: Int J Biol Markers. 2009 Oct-Dec;24(4):265-70
references: 20082276
references: Mol Psychiatry. 2005 Jun;10(6):538-44
references: 15494706
references: Nat Med. 2003 Oct;9(10):1269-74
references: 14502282
references: J Psychopharmacol. 2009 May;23(3):287-94
references: 18562404
references: Psychol Med. 2001 Jul;31(5):847-58
references: 11459382
references: Br J Cancer. 2002 Jun 5;86(11):1691-6
references: 12087451
references: Ann Oncol. 2006 May;17(5):801-6
references: 16507565
references: Gan To Kagaku Ryoho. 2005 Oct;32(11):1546-9
references: 16315864
references: Eur Arch Psychiatry Clin Neurosci. 1997;247(3):154-61
references: 9224908
references: J Affect Disord. 2007 Sep;102(1-3):65-72
references: 17270276
references: Crit Rev Oncol Hematol. 2007 Sep;63(3):183-202
references: 17678745
references: Nat Med. 2005 Mar;11(3):312-9
references: 15711557
references: Nurs Res. 2008 Jan-Feb;57(1):51-8
references: 18091292
references: Oncol Rep. 2007 Jun;17(6):1333-9
references: 17487387
references: Nat Rev Drug Discov. 2002 Aug;1(8):609-20
references: 12402501
references: Nat Rev Cancer. 2005 Apr;5(4):263-74
references: 15776005
references: Mol Psychiatry. 2002;7(5):468-73
references: 12082564
references: J Psychiatry Neurosci. 2000 Sep;25(4):371-7
references: 11022402
references: J Child Psychol Psychiatry. 1987 Nov;28(6):885-900
references: 3436995
references: BMC Gastroenterol. 2009 Jan 20;9:6
references: 19154614
references: Psychiatry Res. 1994 Nov;54(2):143-60
references: 7761549
references: J Clin Oncol. 2008 Feb 20;26(6):971-82
references: 18281672
references: Clin Chim Acta. 2006 Feb;364(1-2):82-90
references: 16139256
references: Curr Opin Clin Nutr Metab Care. 2011 Jan;14(1):49-56
references: 21076293
references: J Biol Chem. 1996 Aug 9;271(32):19140-5
references: 8702590
references: Cancer Nurs. 2005 May-Jun;28(3):219-25
references: 15915067
references: Breast Cancer Res Treat. 2009 Jul;116(1):113-23
references: 18629633
references: Life Sci. 1997;60(12):899-907
references: 9061047