{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:45:23Z","timestamp":1791146723810,"version":"4.1.0"},"reference-count":28,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"28","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCO"],"published-print":{"date-parts":[[2009,10,1]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p> The primary objectives of this phase I\/II study were to evaluate the safety and immunogenicity of combination therapy consisting of concurrent trastuzumab and human epidermal growth factor receptor 2 (HER2)\/neu-specific vaccination in patients with HER2\/neu-overexpressing metastatic breast cancer. <\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p> Twenty-two patients with stage IV HER2\/neu-positive breast cancer receiving trastuzumab therapy were vaccinated with an HER2\/neu T-helper peptide-based vaccine. Toxicity was graded according to National Cancer Institute criteria, and antigen specific T-cell immunity was assessed by interferon gamma enzyme-linked immunosorbent spot assay. Data on progression-free and overall survival were collected. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p> Concurrent trastuzumab and HER2\/neu vaccinations were well tolerated, with 15% of patients experiencing an asymptomatic decline in left ventricular ejection fraction below the normal range during combination therapy. Although many patients had pre-existing immunity specific for HER2\/neu and other breast cancer antigens while treated with trastuzumab alone, that immunity could be significantly boosted and maintained with vaccination. Epitope spreading within HER2\/neu and to additional tumor-related proteins was stimulated by immunization, and the magnitude of the T-cell response generated was significantly inversely correlated with serum transforming growth factor beta levels. At a median follow-up of 36 months from the first vaccine, the median overall survival in the study population has not been reached. <\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p> Combination therapy with trastuzumab and a HER2\/neu vaccine is associated with minimal toxicity and results in prolonged, robust, antigen-specific immune responses in treated patients. <\/jats:p><\/jats:sec>","DOI":"10.1200\/jco.2008.20.6789","type":"journal-article","created":{"date-parts":[[2009,9,1]],"date-time":"2009-09-01T01:55:11Z","timestamp":1251770111000},"page":"4685-4692","source":"Crossref","is-referenced-by-count":278,"title":["Concurrent Trastuzumab and HER2\/<i>neu<\/i>-Specific Vaccination in Patients With Metastatic Breast Cancer"],"prefix":"10.1200","volume":"27","author":[{"given":"Mary L.","family":"Disis","sequence":"first","affiliation":[{"name":"From the Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington; Fred Hutchinson Cancer Research Center, Seattle, WA; and Breastlink Medical Group, Long Beach, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danelle R.","family":"Wallace","sequence":"additional","affiliation":[{"name":"From the Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington; Fred Hutchinson Cancer Research Center, Seattle, WA; and Breastlink Medical Group, Long Beach, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore A.","family":"Gooley","sequence":"additional","affiliation":[{"name":"From the Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington; Fred Hutchinson Cancer Research Center, Seattle, WA; and Breastlink Medical Group, Long Beach, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushe","family":"Dang","sequence":"additional","affiliation":[{"name":"From the Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington; Fred Hutchinson Cancer Research Center, Seattle, WA; and Breastlink Medical Group, Long Beach, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith","family":"Slota","sequence":"additional","affiliation":[{"name":"From the Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington; Fred Hutchinson Cancer Research Center, Seattle, WA; and Breastlink Medical Group, Long Beach, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hailing","family":"Lu","sequence":"additional","affiliation":[{"name":"From the Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington; Fred Hutchinson Cancer Research Center, Seattle, WA; and Breastlink Medical Group, Long Beach, CA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew L.","family":"Coveler","sequence":"additional","affiliation":[{"name":"From the Tumor Vaccine Group, Center for Translational Medicine in Women's Health, University of Washington; Fred Hutchinson Cancer Research Center, Seattle, WA; 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