TY - JOUR
T1 - Overexpression of the EMT driver brachyury in breast carcinomas
T2 - Association with poor prognosis
AU - Palena, Claudia
AU - Roselli, Mario
AU - Litzinger, Mary T.
AU - Ferroni, Patrizia
AU - Costarelli, Leopoldo
AU - Spila, Antonella
AU - Cavaliere, Francesco
AU - Huang, Bruce
AU - Fernando, Romaine I.
AU - Hamilton, Duane H.
AU - Jochems, Caroline
AU - Tsang, Kwong Yok
AU - Cheng, Qing
AU - Lyerly, H. Kim
AU - Schlom, Jeffrey
AU - Guadagni, Fiorella
PY - 2014/5/14
Y1 - 2014/5/14
N2 - 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.
AB - 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.
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U2 - 10.1093/jnci/dju054
DO - 10.1093/jnci/dju054
M3 - Article
C2 - 24815864
AN - SCOPUS:84905171394
VL - 106
JO - Journal of the National Cancer Institute
JF - Journal of the National Cancer Institute
SN - 0027-8874
IS - 5
M1 - dju054
ER -