P4-08-03: Serum Autoantibodies to Breast Cancer Associated Antigens Reflect Tumor Biology: An Opportunity for Early Detection & Prevention?

Abstract

Abstract Autoantibodies (AABs) are produced as an immune response to abnormal ('non-self') cancer antigens. Previous studies have reported that AABs can be measured in the blood long before cancers are presently diagnosed, e.g., up to 4 years before screening mammography identified breast cancers and up to 5 years before screening CT detected lung cancers. EarlyCDT™-Lung is currently available as an aid to early detection of lung cancer in high risk patients and measures a panel of seven AABs to general cancer antigens and also lung cancer (LC) specific antigens. These AABs have previously been reported to be associated with the two main types of LC i.e., non-small cell and small cell LC. This study looked at AABs to 4 general cancer antigens to evaluate whether their levels reflected different biology in primary breast tumors. Methods 770 patients presented with primary breast cancer to three centers (Nottingham, UK n=323; Munich, Germany n=320; Oklahoma, USA n=127); the median ages and ranges were 61 (26-82), 61 (20-88) & 65 (54-84) years, respectively. All had serum samples taken post-diagnosis and pre-treatment. The tumors were well characterized for histological grade, estrogen receptor (ER), progesterone receptor (PgR) and HER2 status. Serum samples were tested for AABs to four generic cancer antigens(Ags) (p53, SOX2, NY-ESO-1 and Annexin1) originally included as part of Oncimmune's EarlyCDT™-Lung assay. The AABs were measured by ELISA on the Oncimmune platform, and the EarlyCDT™-Lung cutoffs were used to determine positivity. Results 131/770 (17%) of primary breast cancers showed elevated AAB levels to one or more of the limited panel of four generic antigens. Positivity for each AAB was correlated with histological grade, ER, PgR and HER2 status. The results, which were similar for each of the three centres, were combined, and the results are shown in Table 1 below. p53 AAB positive cancers tended to be hormone receptor negative and HER2 positive. NY-ESO-1 positive tumors were almost all higher grade with the majority hormone receptor and HER2 negative. SOX2 positive cancers tended to have a hormone sensitive phenotype (i.e., hormone receptor positive and HER2 negative). Annexin 1 positive cancers also tended to have a hormone sensitive phenotype as well as HER2 negative. The pattern was statistically different for the four AABs (p<0.001). The autoantibody profile for ER positive tumours was not statistically different from PgR positive tumors. Conclusions These data show that specific AABs measured in the serum reflected the biology of the breast cancers. Confirmation of this finding could, in the future, lead to using immuno-biomarkers such as these to guide early therapeutic intervention (e.g. prevention) in a targeted group of women. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-08-03.