HER2/neu (HER2) specific T-cell immunity in patients with HER2+ inflammatory breast cancer (IBC) and prognosis

Abstract

3057 Background: IBC is rare, highly aggressive, and associated with worse prognosis when compared to non-IBC tumors. Moreover, multimodality treatment has had little impact on overall prognosis. HER2 is overexpressed in about 40% of IBC tumors and is associated with worse overall survival (OS). We have developed vaccines that elicit both HER2-specific CD4+ and CD8+ T-cell immunity in HER2+ cancer patients. Generation of HER2-specific T-cell immunity could (1) target immunogenic and biologically relevant proteins such as HER2 in IBC, (2) result in immunogenic eradication of HER2+ tumor cells, and (3) potentially prevent disease relapse when used in the adjuvant setting after standard therapy. A retrospective analysis of IBC patients immunized with HER2 vaccines was conducted to better understand the development of HER2-specific T-cell immunity and its possible impact on overall prognosis in IBC. Methods: Clinical and immunological data of IBC patients enrolled in University of Washington IRB approved HER2 vaccine trials was collected and reviewed. 27 patients immunized between 1996–2008 were identified; and 24/27 subjects who received vaccines designed to elicit both CD4+/CD8+ immunity were included in immunologic and survival analysis. The 24 subjects received either a HER2 DNA or HER2 peptide-based vaccine that were admixed with GM-CSF and given intradermally monthly for a total of 3 DNA or 6 peptide vaccines. Immune responses were assessed via IFN-γ ELISPOT at baseline and post-vaccination. Results: All 24 subjects had stage III IBC and median age was 48 (range 34–77). 10/24 (42%) patients had ER/PR+ tumors, 9/24 (37%) had received trastuzumab, and 15/24 (62%) had received multimodality treatment (chemotherapy, mastectomy, radiotherapy). 12/18 subjects (66%) evaluable for immunologic response developed HER2-specific T-cell immunity post-vaccination. Median OS for patients (n=6) not generating HER2-specific immunity was 31 months and median OS for the 12 patients who developed HER2-specific immunity has not been reached at median follow-up of 46 months, (p=0.026). Conclusions: Patients with IBC are able to generate HER2-specific T-cell immunity after HER2 vaccination, and development of HER2-specific immunity may impact survival. No significant financial relationships to disclose.