supplementary tables S1-11. Table S1. Established breast cancer risk factors in the Polish Breast Cancer Study (basal-like, n=145; control, n=145)a. Table S2. AAb responses based on quantitative analysis in each sample from sample set 1. Table S3. AAb responses based on visual analysis in each sample from sample set 1. Table S4. List of proteins selected for focused array Table S5. List of 14 antigens selected from focused array experiments. Individual sensitivities were determined at 98% specificity (Sample set 2: basal-like, n=50; control, n=50). Table S6. List of proteins selected for ELISA verification Table S7. List of 15 antigens selected from ELISA verification. Individual sensitivities were determined at 98% specificity. (Sample set 1: basal-like, n=43; control, n=43). Table S8. 13-AAb classifier. Table S9. Performance of 13 AAbs in multiple breast cancer subtypes. (Basal-like, n=145; luminal A, n=30; luminal B, n=22; her2-enriched, n=18; control, n=145). Table S10. Relationship between TP53 AAb response and TP53 tissue IHC score in basal-like breast cancers. Table S11. Hazard ratios for 2 antigen AAb responses that are significantly associated with survival amongst 145 basal like breast cancers.
ARTICLE ABSTRACT
Background: Basal-like breast cancer (BLBC) is a rare aggressive subtype that is less likely to be detected through mammographic screening. Identification of circulating markers associated with BLBC could have promise in detecting and managing this deadly disease.Methods: Using samples from the Polish Breast Cancer study, a high-quality population-based case–control study of breast cancer, we screened 10,000 antigens on protein arrays using 45 BLBC patients and 45 controls, and identified 748 promising plasma autoantibodies (AAbs) associated with BLBC. ELISA assays of promising markers were performed on a total of 145 BLBC cases and 145 age-matched controls. Sensitivities at 98% specificity were calculated and a BLBC classifier was constructed.Results: We identified 13 AAbs (CTAG1B, CTAG2, TP53, RNF216, PPHLN1, PIP4K2C, ZBTB16, TAS2R8, WBP2NL, DOK2, PSRC1, MN1, TRIM21) that distinguished BLBC from controls with 33% sensitivity and 98% specificity. We also discovered a strong association of TP53 AAb with its protein expression (P = 0.009) in BLBC patients. In addition, MN1 and TP53 AAbs were associated with worse survival [MN1 AAb marker HR = 2.25, 95% confidence interval (CI), 1.03–4.91; P = 0.04; TP53, HR = 2.02, 95% CI, 1.06–3.85; P = 0.03]. We found limited evidence that AAb levels differed by demographic characteristics.Conclusions: These AAbs warrant further investigation in clinical studies to determine their value for further understanding the biology of BLBC and possible detection.Impact: Our study identifies 13 AAb markers associated specifically with BLBC and may improve detection or management of this deadly disease. Cancer Epidemiol Biomarkers Prev; 24(9); 1332–40. ©2015 AACR.
