Survival in early breast cancer patients is favorably influenced by a natural humoral immune response to polymorphic epithelial mucin

Purpose: Polymorphic epithelial mucin (PEM or MUCI) is being studied as a v accine substrate for the immunotherapy of patients with adenocarcinoma. The present study analyzes the incidence of naturally occurring MUC1 antibodie s in early breast cancer patients and relates the presence of these antibod ies in pretreatment serum to outcome of disease. Materials and Methods: We measured immunoglobulin G (IgG) and immunoglobuli n M (IgM) antibodies to MUC1 with an enzyme-linked immunoassay (PEM.CIg), w hich uses a MUC1 triple-tandem repeat peptide conjugated to bovine serum al bumin, in pretreatment serum samples obtained from 154 breast cancer patien ts (52 with stage I disease and 102 with stage II) and 302 controls. The me dian disease-specific survival time of breast cancer patients was 74 months (range, 15 to 118 months). A positive test result war defined as MUC1 IgG or IgM antibody levels equal to or greater than the corresponding rounded-u p median results obtained in the total breast cancer population. Results: A positive test result for both MUC1 IgG and IgM antibodies in pre treatment serum was associated with a significant benefit in disease-specif ic survival in stage I and II (P = .0116) breast cancer patients. Positive IgG and IgM MUC1 antibody levels had significant additional prognostic valu e to stage (P = .0437) in multivariate analysis. Disease-free survival prob ability did not differ significantly. However, stage II patients who tested positive for MUC1 IgG and IgM antibody and who relapsed had predominantly local recurrences or contralateral disease, as opposed to recurrences at di stant sites in the patients with a negative humoral response (P = .026). Conclusion: Early breast cancer patients with a natural humoral response to MUC1 have a higher probability of freedom from distant failure and a bette r disease-specific survival. MUC1 antibodies may control hematogenic tumor dissemination and outgrowth by aiding the destruction of circulating or see ded MUC1-expressing tumor cells. Vaccination of breast cancer patients with MUC1-derived (glyco)peptides in an adjuvant setting may favorably influenc e the outcome of disease. J Clin Oncol 18:574-583. (C) 2000 by American Soc iety of Clinical Oncology.