title: Pilot phase III immunotherapy study in early-stage breast cancer patients using oxidized mannan-MUC1 [ISRCTN71711835].
abstract: BACKGROUND
  Mucin 1 (MUC1) is a high molecular weight glycoprotein overexpressed on adenocarcinoma cells and is a target for immunotherapy protocols. To date, clinical trials against MUC1 have included advanced cancer patients. Herein, we report a trial using early stage breast cancer patients and injection of oxidized mannan-MUC1.
  
  
  METHODS
  In a randomized, double-blind study, 31 patients with stage II breast cancer and with no evidence of disease received subcutaneous injections of either placebo or oxidized mannan-MUC1, to immunize against MUC1 and prevent cancer reoccurrence/metastases. Twenty-eight patients received the full course of injections of either oxidized mannan-MUC1 or placebo. Survival and immunological assays were assessed.
  
  
  RESULTS
  After more than 5.5 years had elapsed since the last patient began treatment (8.5 years from the start of treatment of the first patient), the recurrence rate in patients receiving the placebo was 27% (4/15; the expected rate of recurrence in stage II breast cancer); those receiving immunotherapy had no recurrences (0/16), and this finding was statistically significant (P = 0.0292). Of the patients receiving oxidized mannan-MUC1, nine out of 13 had measurable antibodies to MUC1 and four out of 10 had MUC1-specific T cell responses; none of the placebo-treated patients exhibited an immune response to MUC1.
  
  
  CONCLUSIONS
  The results suggest that, in early breast cancer, MUC1 immunotherapy is beneficial, and that a larger phase III study should be undertaken.
authors.affiliation: Immunology and Vaccine Laboratory, Burnet Institute at Austin, Heidelberg, Victoria, Australia. vasso@burnet.edu.au
authors.forename: Vasso
authors.initials: V
authors.lastname: Apostolopoulos
authors.forename: Geoffrey A
authors.initials: GA
authors.lastname: Pietersz
authors.forename: Anastasios
authors.initials: A
authors.lastname: Tsibanis
authors.forename: Annivas
authors.initials: A
authors.lastname: Tsikkinis
authors.forename: Heleni
authors.initials: H
authors.lastname: Drakaki
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Loveland
authors.forename: Sara J
authors.initials: SJ
authors.lastname: Piddlesden
authors.forename: Magdalena
authors.initials: M
authors.lastname: Plebanski
authors.forename: Dodie S
authors.initials: DS
authors.lastname: Pouniotis
authors.forename: Michael N
authors.initials: MN
authors.lastname: Alexis
authors.forename: Ian F
authors.initials: IF
authors.lastname: McKenzie
authors.forename: Stamatis
authors.initials: S
authors.lastname: Vassilaros
mesh_terms: D000230:Adenocarcinoma / Q000473:pathology / Q000628:therapy*; D000368:Aged; D000369:Aged, 80 and over; D000917:Antibody Formation; D001943:Breast Neoplasms / Q000473:pathology / Q000628:therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D008351:Mannans / Q000276:immunology / Q000627:therapeutic use*; D008875:Middle Aged; D018396:Mucin-1 / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D008351:Mannans; D018396:Mucin-1