Abstract 2224: Panel of autoantibodies to seven early tumor-associated overexpressed proteins can identify women with DCIS from women with benign breast tumors detected by mammography

Abstract

Abstract While mammography is essential to identify early breast cancer, the sensitivity is dependent on breast characteristics. Currently all breast masses identified by mammography have to be biopsied to determine if malignant. A serum-based biomarker used along with mammography to identify pre-malignant lesions to biopsy would both improve the sensitivity of mammography and reduce the number of biopsies needed. We have identified a panel of autoantibodies found in early breast cancer. An autoantibody biomarker is ideal because antibody immunity can be detected with very low levels of antigen with direct antigen recognition by B cells resulting in clonal amplification of antigen specific plasma cells. Work in our laboratory has identified tumor-associated proteins present in pre-malignant tumors that are necessary for survival of human breast cancer cells across breast cancer subtypes. We have found that increased autoantibodies to seven of these early tumor-associated proteins (PDIA6, KRT8, SERBP1, ARPC2, RRM2, AURKA, and NDC80) were present in the sera of women with pre-malignant breast atypia but not women with no breast atypia or benign breast atypia and may be a panel to increase sensitivity of mammography. The presence of autoantibodies was evaluated in 191 individuals, 36 women with no breast atypia, 12 women with benign breast atypia, 36 patients with fibroadenoma, 12 patients with hyperplasia, 59 patients with ductal carcinoma in situ (DCIS), and 36 patients with invasive breast cancer (IBC). We found more women with pre-malignant breast atypia had increased autoantibodies to at least one of the seven early tumor associated proteins as compared to women with either no breast atypia or benign breast atypia. For example, a positive autoantibody response is over 2 standard deviations above the mean found in women with no breast atypia. There were 2.9% of women with positive autoantibody response to RRM2 in women without breast atypia. However, in women with breast atypia, there was a positive antibody response in 41.7% of individuals with hyperplasia, 48.6% of individuals with fibroadenoma, 34.5% of individuals with DCIS, and 28.6% of individuals with IBC. All seven autoantibodies could predict patients with hyperplasia, fibroadenoma, DCIS, and IBC from both women with no atypia and women with benign breast atypia. For example, the seven-antibody panel could identify DCIS from women with no breast atypia with AUC of 0.95 (95% CI 0.912 to 0.995) and from women with benign breast atypia with AUC of 0.71 (95% CI 0.519 to 0.898). This is a better AUC than seen with previous published autoantibody profiles in DCIS. Future studies will validate these findings with the goal of developing a serum biomarker that will improve sensitivity of mammography. Citation Format: Sasha Elizabeth Stanton, Erik Ramos, Mary L. Disis. Panel of autoantibodies to seven early tumor-associated overexpressed proteins can identify women with DCIS from women with benign breast tumors detected by mammography [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2224.