HIGH-TITER HER-2 NEU PROTEIN-SPECIFIC ANTIBODY CAN BE DETECTED IN PATIENTS WITH EARLY-STAGE BREAST-CANCER/

Purpose: To evaluate HER-2/neu-specific antibody immunity patients wit h breast cancer, to determine the rate of occurrence of serum antibodi es to HER-2/neu in patients with breast cancer, and to relate the pres ence of specific immunity to overexpression of HER-2/neu protein in pr imary tumor. Methods: The antibody response to HER-2/neu protein was a nalyzed in 107 newly diagnosed breast cancer patients. Sera was analyz ed for the presence of HER-SI neo-specific antibodies with a capture e nzyme-linked immunosorbent assay (ELISA) and verified by Western blot. Sera from 200 volunteer blood donors was used as a control population . Results: The presence of antibodies to HER-2/neu correlated with the presence of breast cancer. HER-2/neu antibodies at titers of greater than or equal to 1:100 were detected in 12 of 107 (11%) breast cancer patients versus none of 200 (O%) normal controls (P <.01). The presenc e of antibodies to HER-2/neu also correlated to overexpression of HER- 2/neu protein in the patient's primary tumor. Nine of 44 (20%) patient s with HER-2/neu-positive tumors had HER-2/neu-specific antibodies, wh ereas three of 63 (5%) patients with HER-2/neu-negative tumors had ant ibodies (P = .03). The antibody responses could be substantial. Titers of greater than 1:5,000 were detected in five of 107 (5%). Conclusion : The presence of HER-2/neu antibodies in breast cancer patients and t he correlation with HER-2/neu-positive cancer implies that immunity to HER-2/neu develops as a result of exposure of patients to HER-2/neu p rotein expressed by their own cancer. These findings should stimulate further studies to develop the detection of immunity to oncogenic prot eins as tumor markers, as well as the development and testing of vacci ne strategies to induce and augment immunity to HER-2/neu for the trea tment of breast cancer or prevention of recurrent disease. (C) 1997 by American Society of Clinical Oncology.