Whereas the serum assay (CA15.3) used for detecting the cancer associated MUC1 antigen in breast cancer patient serum does not detect elevated antigen in early stage breast cancer, autoantibodies to specific tumour-associated glycoforms of MUC1 can be detected in sera from Stage I and Stage II breast cancer patients. The difference in the percentage of sera strongly positive for the antibodies in cancer patient sera versus sera from patients with benign disease or from healthy individuals who never developed cancer is highly significant. Follow-up of patients with benign breast disease with sera with high levels of autoantibodies may be appropriate. The lower incidence of metastases and delay in development of metastases in patients with high levels of antibodies to a subset of the glycoforms, suggests that the antibodies may play a role in inhibiting the progression of disease. Administration of antibodies with these specificities is, therefore, a possible therapeutic strategy. This would be particularly appropriate for breast cancer patients with STn positive cancers (25 to 30% of breast cancer patients) as the STnMUC1 glycoform is truly tumour specific.
ACTB: β-actin; Gal: galactose; GI: gastrointestinal: PB: print buffer; PBS, phosphate buffered saline; ROC: receiving operational characteristic; SDs: standard deviations.
This work was supported by grants from the European Union under the FP7 framework grant agreement number 201381, the NIH (PO1 CA052477 1U01CA128437-01), The Benzon Foundation, The Carlsberg Foundation, the Danish Research Council, the Danish Agency for Science, Technology and Innovation (FTP) and a centre of Excellence program from University of Copenhagen. The authors also acknowledge financial support from the Department of Health via the National Institute for Health Research (NIHR) comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust.
OB contributed to the strategic plan and design of the experiments, developed the array assay and on-chip glycosylation methods, and contributed to the writing of the manuscript. DB performed most of the screening for antibodies in the sera of the large cohorts of breast cancer patients, patients with benign disease and healthy adults. BB performed the statistical analysis of the data obtained from the screening assays. DA selected the sera from the healthy adults, provided the clinical data for the breast cancer patients, and analysed the relation between clinical parameters and presence of antibodies. SJ analysed the levels of the core3 and C1GalT transferases in breast cancers and colon. MH contributed to the strategic plan of the work. AG oversaw the statistical analysis of the data generated. IF provided the follow-up data for the healthy controls and contributed to the design of the experiments. JTP contributed to the strategic plan and design of the experiments, and to the writing of the first draft and subsequent drafts of the manuscript. JB contributed to the strategic plan and design of the experiments, and to the writing of the first draft and subsequent drafts of the manuscript. All authors read and approved the final manuscript
OB has shares in GlycoZym, Inc. and is a consultant for GlycoZym, Inc. The other authors declare that they have no competing interests.
Breast Cancer Res. 2011;13(2):R25 © 2011 BioMed Central, Ltd.
Copyright to this article is held by the author(s), licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original citation.
Cite this: Autoantibodies to Aberrantly Glycosylated MUC1 in Early Stage Breast Cancer are Associated with a Better Prognosis - Medscape - Mar 18, 2011.