title: Overexpression of the EMT driver brachyury in breast carcinomas: association with poor prognosis.
abstract: 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.
authors.affiliation: Affiliations of authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CP, MTL, BH, RIF, DHH, CJ, K-YT, JS); Department of Internal Medicine, Medical Oncology Unit, Tor Vergata University, Rome, Italy (MR); Interinstitutional Multidisciplinary Biobank, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy (PF, AS, FG); Department of Pathology (LC) and Department of Surgery (FC), San Giovanni Addolorata Hospital, Rome, Italy; Department of Surgery, Duke University School of Medicine, Durham, NC (QC, HKL).
authors.forename: Claudia
authors.initials: C
authors.lastname: Palena
authors.affiliation: Affiliations of authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CP, MTL, BH, RIF, DHH, CJ, K-YT, JS); Department of Internal Medicine, Medical Oncology Unit, Tor Vergata University, Rome, Italy (MR); Interinstitutional Multidisciplinary Biobank, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy (PF, AS, FG); Department of Pathology (LC) and Department of Surgery (FC), San Giovanni Addolorata Hospital, Rome, Italy; Department of Surgery, Duke University School of Medicine, Durham, NC (QC, HKL).
authors.forename: Mario
authors.initials: M
authors.lastname: Roselli
authors.affiliation: Affiliations of authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CP, MTL, BH, RIF, DHH, CJ, K-YT, JS); Department of Internal Medicine, Medical Oncology Unit, Tor Vergata University, Rome, Italy (MR); Interinstitutional Multidisciplinary Biobank, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy (PF, AS, FG); Department of Pathology (LC) and Department of Surgery (FC), San Giovanni Addolorata Hospital, Rome, Italy; Department of Surgery, Duke University School of Medicine, Durham, NC (QC, HKL).
authors.forename: Mary T
authors.initials: MT
authors.lastname: Litzinger
authors.affiliation: Affiliations of authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CP, MTL, BH, RIF, DHH, CJ, K-YT, JS); Department of Internal Medicine, Medical Oncology Unit, Tor Vergata University, Rome, Italy (MR); Interinstitutional Multidisciplinary Biobank, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy (PF, AS, FG); Department of Pathology (LC) and Department of Surgery (FC), San Giovanni Addolorata Hospital, Rome, Italy; Department of Surgery, Duke University School of Medicine, Durham, NC (QC, HKL).
authors.forename: Patrizia
authors.initials: P
authors.lastname: Ferroni
authors.affiliation: Affiliations of authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CP, MTL, BH, RIF, DHH, CJ, K-YT, JS); Department of Internal Medicine, Medical Oncology Unit, Tor Vergata University, Rome, Italy (MR); Interinstitutional Multidisciplinary Biobank, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy (PF, AS, FG); Department of Pathology (LC) and Department of Surgery (FC), San Giovanni Addolorata Hospital, Rome, Italy; Department of Surgery, Duke University School of Medicine, Durham, NC (QC, HKL).
authors.forename: Leopoldo
authors.initials: L
authors.lastname: Costarelli
authors.affiliation: Affiliations of authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CP, MTL, BH, RIF, DHH, CJ, K-YT, JS); Department of Internal Medicine, Medical Oncology Unit, Tor Vergata University, Rome, Italy (MR); Interinstitutional Multidisciplinary Biobank, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy (PF, AS, FG); Department of Pathology (LC) and Department of Surgery (FC), San Giovanni Addolorata Hospital, Rome, Italy; Department of Surgery, Duke University School of Medicine, Durham, NC (QC, HKL).
authors.forename: Antonella
authors.initials: A
authors.lastname: Spila
authors.affiliation: Affiliations of authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CP, MTL, BH, RIF, DHH, CJ, K-YT, JS); Department of Internal Medicine, Medical Oncology Unit, Tor Vergata University, Rome, Italy (MR); Interinstitutional Multidisciplinary Biobank, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy (PF, AS, FG); Department of Pathology (LC) and Department of Surgery (FC), San Giovanni Addolorata Hospital, Rome, Italy; Department of Surgery, Duke University School of Medicine, Durham, NC (QC, HKL).
authors.forename: Francesco
authors.initials: F
authors.lastname: Cavaliere
authors.affiliation: Affiliations of authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CP, MTL, BH, RIF, DHH, CJ, K-YT, JS); Department of Internal Medicine, Medical Oncology Unit, Tor Vergata University, Rome, Italy (MR); Interinstitutional Multidisciplinary Biobank, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy (PF, AS, FG); Department of Pathology (LC) and Department of Surgery (FC), San Giovanni Addolorata Hospital, Rome, Italy; Department of Surgery, Duke University School of Medicine, Durham, NC (QC, HKL).
authors.forename: Bruce
authors.initials: B
authors.lastname: Huang
authors.affiliation: Affiliations of authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CP, MTL, BH, RIF, DHH, CJ, K-YT, JS); Department of Internal Medicine, Medical Oncology Unit, Tor Vergata University, Rome, Italy (MR); Interinstitutional Multidisciplinary Biobank, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy (PF, AS, FG); Department of Pathology (LC) and Department of Surgery (FC), San Giovanni Addolorata Hospital, Rome, Italy; Department of Surgery, Duke University School of Medicine, Durham, NC (QC, HKL).
authors.forename: Romaine I
authors.initials: RI
authors.lastname: Fernando
authors.affiliation: Affiliations of authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CP, MTL, BH, RIF, DHH, CJ, K-YT, JS); Department of Internal Medicine, Medical Oncology Unit, Tor Vergata University, Rome, Italy (MR); Interinstitutional Multidisciplinary Biobank, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy (PF, AS, FG); Department of Pathology (LC) and Department of Surgery (FC), San Giovanni Addolorata Hospital, Rome, Italy; Department of Surgery, Duke University School of Medicine, Durham, NC (QC, HKL).
authors.forename: Duane H
authors.initials: DH
authors.lastname: Hamilton
authors.affiliation: Affiliations of authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CP, MTL, BH, RIF, DHH, CJ, K-YT, JS); Department of Internal Medicine, Medical Oncology Unit, Tor Vergata University, Rome, Italy (MR); Interinstitutional Multidisciplinary Biobank, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy (PF, AS, FG); Department of Pathology (LC) and Department of Surgery (FC), San Giovanni Addolorata Hospital, Rome, Italy; Department of Surgery, Duke University School of Medicine, Durham, NC (QC, HKL).
authors.forename: Caroline
authors.initials: C
authors.lastname: Jochems
authors.affiliation: Affiliations of authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CP, MTL, BH, RIF, DHH, CJ, K-YT, JS); Department of Internal Medicine, Medical Oncology Unit, Tor Vergata University, Rome, Italy (MR); Interinstitutional Multidisciplinary Biobank, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy (PF, AS, FG); Department of Pathology (LC) and Department of Surgery (FC), San Giovanni Addolorata Hospital, Rome, Italy; Department of Surgery, Duke University School of Medicine, Durham, NC (QC, HKL).
authors.forename: Kwong-Yok
authors.initials: KY
authors.lastname: Tsang
authors.affiliation: Affiliations of authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CP, MTL, BH, RIF, DHH, CJ, K-YT, JS); Department of Internal Medicine, Medical Oncology Unit, Tor Vergata University, Rome, Italy (MR); Interinstitutional Multidisciplinary Biobank, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy (PF, AS, FG); Department of Pathology (LC) and Department of Surgery (FC), San Giovanni Addolorata Hospital, Rome, Italy; Department of Surgery, Duke University School of Medicine, Durham, NC (QC, HKL).
authors.forename: Qing
authors.initials: Q
authors.lastname: Cheng
authors.affiliation: Affiliations of authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CP, MTL, BH, RIF, DHH, CJ, K-YT, JS); Department of Internal Medicine, Medical Oncology Unit, Tor Vergata University, Rome, Italy (MR); Interinstitutional Multidisciplinary Biobank, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy (PF, AS, FG); Department of Pathology (LC) and Department of Surgery (FC), San Giovanni Addolorata Hospital, Rome, Italy; Department of Surgery, Duke University School of Medicine, Durham, NC (QC, HKL).
authors.forename: H Kim
authors.initials: HK
authors.lastname: Lyerly
authors.affiliation: Affiliations of authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CP, MTL, BH, RIF, DHH, CJ, K-YT, JS); Department of Internal Medicine, Medical Oncology Unit, Tor Vergata University, Rome, Italy (MR); Interinstitutional Multidisciplinary Biobank, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy (PF, AS, FG); Department of Pathology (LC) and Department of Surgery (FC), San Giovanni Addolorata Hospital, Rome, Italy; Department of Surgery, Duke University School of Medicine, Durham, NC (QC, HKL). js141c@nih.gov.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
authors.affiliation: Affiliations of authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD (CP, MTL, BH, RIF, DHH, CJ, K-YT, JS); Department of Internal Medicine, Medical Oncology Unit, Tor Vergata University, Rome, Italy (MR); Interinstitutional Multidisciplinary Biobank, Department of Laboratory Medicine and Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy (PF, AS, FG); Department of Pathology (LC) and Department of Surgery (FC), San Giovanni Addolorata Hospital, Rome, Italy; Department of Surgery, Duke University School of Medicine, Durham, NC (QC, HKL).
authors.forename: Fiorella
authors.initials: F
authors.lastname: Guadagni
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D005326:Fetal Proteins / Q000096:biosynthesis* / Q000235:genetics; D005557:Formaldehyde; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016612:Paraffin Embedding; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020825:T-Box Domain Proteins / Q000096:biosynthesis* / Q000235:genetics; D016707:Tissue Fixation; D000098908:Brachyury Protein
chemical_list: D005326:Fetal Proteins; D005557:Formaldehyde; D012333:RNA, Messenger; D020825:T-Box Domain Proteins; D000098908:Brachyury Protein