Overexpression of the EMT driver brachyury in breast carcinomas: association with poor prognosis.

Journal Article (Journal Article)

BACKGROUND: The epithelial-mesenchymal transition (EMT) has been implicated as an important process in tumor cell invasion, metastasis, and drug resistance. The transcription factor brachyury has recently been described as a driver of EMT of human carcinoma cells. METHODS: Brachyury mRNA and protein expression was analyzed in human breast carcinomas and benign tissues. The role of brachyury in breast tumor prognosis and drug resistance and the ability of brachyury-specific T cells to lyse human breast carcinoma cells were also evaluated. Kaplan-Meier analyses were used to evaluate the association between brachyury expression and survival. All statistical tests were two-sided. RESULTS: The level of brachyury expression in breast cancer cells was positively associated with their ability to invade the extracellular matrix, efficiently form mammospheres in vitro, and resist the cytotoxic effect of docetaxel. A comparison of survival among breast cancer patients treated with tamoxifen in the adjuvant setting who had tumors with high vs low brachyury mRNA expression demonstrated that high expression of brachyury is associated as an independent variable with higher risk of recurrence (hazard ratio [HR] = 7.5; 95% confidence interval [CI] = 2.4 to 23.5; P = 5.14×10(-4)) and distant metastasis (HR = 15.2; 95% CI = 3.5 to 66.3; P = 3.01×10(-4)). We also demonstrated that brachyury-specific T cells can lyse human breast carcinoma cells. CONCLUSIONS: The studies reported here provide the rationale for the use of a vaccine targeting brachyury for the therapy of human breast cancer, either as a monotherapy or in combination therapies.

Full Text

Duke Authors

Cited Authors

  • Palena, C; Roselli, M; Litzinger, MT; Ferroni, P; Costarelli, L; Spila, A; Cavaliere, F; Huang, B; Fernando, RI; Hamilton, DH; Jochems, C; Tsang, K-Y; Cheng, Q; Lyerly, HK; Schlom, J; Guadagni, F

Published Date

  • May 9, 2014

Published In

Volume / Issue

  • 106 / 5

PubMed ID

  • 24815864

Pubmed Central ID

  • PMC4568990

Electronic International Standard Serial Number (EISSN)

  • 1460-2105

Digital Object Identifier (DOI)

  • 10.1093/jnci/dju054


  • eng

Conference Location

  • United States