Anti-MUC1 Antibody in Nipple Aspirate Fluids Correlates with Tumor Aggressiveness in Breast Cancer: A Feasibility Study

Antibodies against MUC1 are found in circulation of breast cancer (BC) patients. We hypothesized that anti-MUC1 antibodies might be present in even a higher concentration in nipple aspirate fluid (NAF) and could be used to predict aggressiveness of BC. Serum and NAF samples were collected from high risk lesions, BC, and healthy contralateral breasts. ELISA was used to measure the amount of IgG, IgM, and IgA against a tumor-specific MUC1 peptide derived from the extracellular tandem repeat domain of MUC1. Tumor characteristics were recorded prospectively; 120 NAF samples were obtained from a total of 77 women in the study. There was no significant difference of anti-MUC1 antibody levels compared to BC with other lesions. Anti-MUC1 IgG level in NAF was higher in triple negative tumors (P=0.02); serum anti-MUC1 IgG levels were significantly higher in patients with ER (−) tumor and recurrent disease (P=0.01); NAF anti-MUC1 IgA levels were significantly higher in patients with LVI and Her2-neu (+) tumors (P<0.05). These results show that NAF could be a reliable biomarker to predict tumor aggressiveness in BC. A larger study will be needed to confirm these data and to investigate the potential of anti-MUC1 antibodies in NAF and serum to predict disease outcome.

Protein Oxidation in Breast Microenvironment: Nipple Aspirate Fluid Collected from Breast Cancer Women Contains Increased Protein Carbonyl Concentration

Background: Protein carbonyl levels are the most frequently used biomarker of protein oxidation in several human diseases, including cancer. Breast cancer, a worldwide disease with increasing incidence, develops from ductal/lobular epithelium from which nipple aspirate fluid can be collected and analysed to assess tissue metabolic activity. Our aims were to perform an exploratory investigation on the protein carbonyl accumulation in breast secretions from healthy and cancer patients and its correlation with lipid peroxidation markers.Methods: Protein carbonyls were determined by ELISA in 288 Nipple Aspirate Fluids (NAF) from Control, Pre-malignant and Cancer patients.Results: Significantly higher protein carbonyl concentration was found in NAF from breast cancer (BC) patients compared to Control subjects. Cancer patients accumulated in NAF significantly higher levels of carbonyls in post-menopausal condition. A significant inverse relationship between carbonyls and 8-F2α-isoprostanes in NAF was found in Cancer patients. NAF levels of protein carbonyls are significantly higher in women with pre-malignant conditions than in healthy subjects.Conclusions: Our results support the hypothesis that oxidative stress in breast microenvironment plays a role in breast cancer; measurement of protein and lipid oxidative products in NAF may improve the identification of women at increased breast cancer risk.