title: Expression of a-Tocopherol-Associated protein (TAP) is associated with clinical outcome in breast cancer patients.
abstract: BACKGROUND
  The role of vitamin E in breast cancer prevention and treatment has been widely investigated, and the different tocopherols that comprise this nutrient have been shown to have divergent associations with cancer outcome. Our previous studies have shown that α-Tocopherol-associated protein (TAP), a vitamin E binding protein, may function as a tumor suppressor-like factor in breast carcinogenesis. The current study addresses the association of TAP expression with breast cancer clinical outcomes.
  
  
  METHODS
  Immunohistochemical stain for TAP was applied to a tissue microarray from a breast cancer cohort consisting of 271 patients with a median follow-up time of 5.2 years. The expression of TAP in tumor cells was compared with patient's clinical outcome at 5 years after diagnosis. The potential role of TAP in predicting outcome was also assessed in clinically relevant subsets of the cohort. In addition, we compared TAP expression and Oncotype DX scores in an independent breast cancer cohort consisting of 71 cases.
  
  
  RESULTS
  We demonstrate that the expression of TAP was differentially expressed within the breast cancer cohort, and that ER+/PR ± tumors were more likely to exhibit TAP expression. TAP expression was associated with an overall lower recurrence rate and a better 5-year survival rate. This association was primarily in patients with ER+ tumors; exploratory analysis showed that this association was strongest in patients with node-positive tumors and was independent of stage and treatment with chemotherapy. TAP expression in ER/PR negative or triple negative tumors had no association with clinical outcome. In addition, we did not observe an association between TAP expression and Oncotype DX recurrence score.
  
  
  CONCLUSIONS
  The significant positive association we found for α-Tocopherol-associated protein with outcome in breast cancer may help to better define and explain studies addressing α-tocopherol's association with cancer risk and outcome. Additionally, further studies to validate and extend these findings may allow TAP to serve as a breast-specific prognostic marker in breast cancer patients, especially in those patients with ER+ tumors.
authors.affiliation: Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642 USA.
authors.forename: Xi
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute for Genomic and Personalized Medicine, School of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Brian Z
authors.initials: BZ
authors.lastname: Ring
authors.affiliation: Insight Genetics Inc., Nashville, TN USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Seitz
authors.affiliation: CardioDx, Inc., Redwood City, CA USA.
authors.forename: Douglas T
authors.initials: DT
authors.lastname: Ross
authors.affiliation: Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642 USA.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Woolf
authors.affiliation: Conversant Biologics, Huntsville, AL USA.
authors.forename: Rodney A
authors.initials: RA
authors.lastname: Beck
authors.affiliation: Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642 USA.
authors.forename: David G
authors.initials: DG
authors.lastname: Hicks
authors.affiliation: Department of Pathology, University of Rochester Medical Center, Rochester, NY 14642 USA.
authors.forename: Shuyuan
authors.initials: S
authors.lastname: Yeh
keywords: Breast cancer; Vitamin E; α-Tocopherol-associated protein (TAP)