title: Mucin 1-specific B cell immune responses and their impact on overall survival in breast cancer patients.
abstract: Considering the diverse functions of B cells, responses to tumor-associated antigens (TAA) have been thought to be the main source of B cell-mediated antitumor immunity. Polymorphic epithelial mucin (MUC1) is considered one of the most specific TAA in patients with breast cancer. The present study aims to dissect the level and subclasses of naturally occurring anti-MUC1 antibodies in regard to tumor biologic parameters, clinical characteristics and overall survival. In 288 primary, non-metastatic breast cancer patients, pretreatment serum levels of anti-MUC1 immunoglobulin G (IgG) and its subclasses G1-4 as well as immunoglobulin M (IgM) were analyzed via ELISA. With respect to overall survival (Kaplan-Meier analysis), tumor biologic parameters as hormone receptor status, human epidermal growth factor receptor 2 (Her2), Ki-67 expression and tumor grading have been correlated as well as clinical characteristics as nodal involvement, tumor stage and patients' age at the time of diagnosis. Median follow-up time was 148 mo (IQR: 73.1-158.5 mo). A significant increase in IgG antibody titers was correlated highly significantly with an improved overall survival of patients. In multivariate analysis, total IgG proved to be an independent prognostic marker for overall survival (p= 0.002). IgG subclass analysis did not reveal any correlation of IgG1, IgG3 and IgG4 levels with overall survival, while increased immunoglobulin G2 (IgG2) values, although statistically not significant, tended to correlate with prolonged patient survival. MUC1-specific IgM antibodies were shown not to be predictive of overall survival. Altogether, humoral immune responses appear to play a crucial part in the tumor immunity of breast cancer patients. The present data confirms the positive impact of tumor-specific IgG on prolonged overall survival in breast cancer patients. MUC1-antibody testing might be a useful tool to identify high-risk patients who may need adjuvant therapy and potentially might benefit from MUC1-directed immunotherapy.
authors.affiliation: Department of Gynecology and Obstetrics; National Center for Tumor Diseases; Heidelberg University Hospital ; Heidelberg, Germany.
authors.forename: Carlo
authors.initials: C
authors.lastname: Fremd
authors.affiliation: Department of Gynecology and Obstetrics; National Center for Tumor Diseases; Heidelberg University Hospital ; Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Stefanovic
authors.affiliation: Division of Translational Immunology; Tumor Immunology Program; German Cancer Research Center ; Heidelberg, Germany.
authors.forename: Philipp
authors.initials: P
authors.lastname: Beckhove
authors.affiliation: Division of Translational Immunology; Tumor Immunology Program; German Cancer Research Center ; Heidelberg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Pritsch
authors.affiliation: Division of Translational Immunology; Tumor Immunology Program; German Cancer Research Center ; Heidelberg, Germany.
authors.forename: Hendry
authors.initials: H
authors.lastname: Lim
authors.affiliation: Department of Gynecology and Obstetrics; National Center for Tumor Diseases; Heidelberg University Hospital ; Heidelberg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Wallwiener
authors.affiliation: Department of Gynecology and Obstetrics; National Center for Tumor Diseases; Heidelberg University Hospital ; Heidelberg, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Heil
authors.affiliation: Department of Gynecology and Obstetrics; National Center for Tumor Diseases; Heidelberg University Hospital ; Heidelberg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Golatta
authors.affiliation: Department of Gynecology and Obstetrics; National Center for Tumor Diseases; Heidelberg University Hospital ; Heidelberg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Rom
authors.affiliation: Department of Gynecology and Obstetrics; National Center for Tumor Diseases; Heidelberg University Hospital ; Heidelberg, Germany.
authors.forename: Christof
authors.initials: C
authors.lastname: Sohn
authors.affiliation: Department of Gynecology and Obstetrics; National Center for Tumor Diseases; Heidelberg University Hospital ; Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Schneeweiss
authors.affiliation: Department of Gynecology and Obstetrics; National Center for Tumor Diseases; Heidelberg University Hospital ; Heidelberg, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Schuetz
authors.affiliation: Department of Gynecology and Obstetrics; National Center for Tumor Diseases; Heidelberg University Hospital ; Heidelberg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Domschke
keywords: ADCC; B cells; MUC1-specific antibodies; breast cancer; immunoglobulin G; prognosis