Assessment of immunologic response and recurrence patterns among patients with clinical recurrence after vaccination with a preventive HER2/neu peptide vaccine:: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02

被引:23
作者
Amin, Asna [2 ]
Benavides, Linda C. [1 ]
Holmes, Jarrod P. [3 ]
Gates, Jeremy D. [1 ]
Carmichael, Mark G. [4 ]
Hueman, Matthew T. [4 ]
Mittendorf, Elizabeth A. [5 ]
Storrer, Catherine E. [4 ]
Jama, Yusuf H. [4 ]
Craig, Dianna [6 ]
Stojadinovic, Alex [2 ]
Ponniah, Sathibalan [4 ]
Peoples, George E. [1 ,4 ]
机构
[1] Brooke Army Med Ctr, Dept Surg, Gen Surg Serv, Ft Sam Houston, TX 78234 USA
[2] Walter Reed Army Med Ctr, Dept Surg, Gen Surg Serv, Washington, DC 20307 USA
[3] USN, San Diego Med Ctr, Div Hematol & Med Oncol, Dept Med, San Diego, CA 92152 USA
[4] Uniformed Serv Univ Hlth Sci, Dept Surg, Canc Vaccine Dev Program, US Mil Canc Inst, Bethesda, MD 20814 USA
[5] UTMD Anderson Canc Ctr, Houston, TX USA
[6] Windber Med Ctr, Joyce Murtha Breast Care Ctr, Windber, PA USA
关键词
vaccine; E75; peptide; preventive; recurrence; pathologic patterns; immunologic response;
D O I
10.1007/s00262-008-0509-2
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background E75, a HER2/neu immunogenic peptide, is expressed in breast cancer (BCa). We have performed clinical trials of E75 + GM-CSF vaccine in disease-free, node-positive and node-negative BCa patients at high recurrence risk and recurrences were noted in both control and vaccine groups. Methods Among the 186 BCa patients enrolled, 177 completed the study. Patients were HLA typed; the HLA-A2(+)/A3(+) patients were vaccinated; HLA-A2(-)/A3(-) patients were followed as controls. Standard clinicopathological factors, immunologic response to the vaccine, and recurrences were collected and assessed. Results The control group recurrence rate was 14.8 and 8.3% in the vaccinated group (P = 0.17). Comparing the 8 vaccinated recurrences (V-R) to the 88 vaccinated nonrecurrent patients (V-NR), the V-R group had higher nodal stage (>= N2: 75 vs. 5%, P = 0.0001) and higher grade tumors (% grade 3: 88 vs. 31%, P = 0.003). The V-R group did not fail to respond immunologically as noted by equivalent dimer responses and post-DTH responses. Compared to control recurrent patients (C-R), V-R patients trended toward higher-grade tumors and hormone-receptor negativity. C-R patients had 50% bone-only recurrences, compared to V-R patients with no bone-only recurrences (P = 0.05). Lastly, V-R mortality rate was 12.5% compared with 41.7% for the C-R group (P = 0.3). Conclusions The vaccinated patients who recurred had more aggressive disease compared to V-NR patients. V-R patients had no difference in immune response to the vaccine either in vitro or in vivo. V-R patients, when compared to C-R patients, trended towards more aggressive disease, decreased recurrence rates, decreased mortality, and no bone-only recurrences.
引用
收藏
页码:1817 / 1825
页数:9
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