Previously, we reported a novel tumor-associated antigen (FAA) derived from human DNA-topoiomerase I (TOP 1). In the present study, we demonstrated that the autoantibody against the TAA could be a potential biomarker in the early diagnosis and favorable prognosis of patients with breast cancer (BC). To understand the survival benefits in BC patients, we investigated whether the autoantibody could induce antibody-dependent cellular cytotoxicity activities (ADCC) against breast cancer cells in vitro. We found that the autoantibody exhibited significant ADCC activities that destroyed breast cancer MCF-7 and MDA-MB-231 cells with peripheral blood mononuclear cells (PBMCs). The ADCC activities of the autoantibody were significantly correlated with the number of natural killer (NK) cells, NKT cells, and CD4(+)/CD8(+) T cells. Accordingly, our findings showed that the autoantibody not only represented an early index of immune response to the TAA, but also was involved in host immune defense mechanisms that initiated the destruction of cancer cells.