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研究者在美國癌症研究學會(AACR)2008年會中報告指出，新的胜肽疫苗可以減少HER2/neu值過度表現乳癌婦女的死亡率達一半。
Johnson&Johnson公司全球血液與腫瘤研發資深副主席、AACR主席William N. Hait博士表示，本研究數量少但是觀念良好；這是好的開始，我們審慎樂觀。
HER2/neu是一種免疫胜肽來源，將近30%的早期乳癌有擴大的HER2/neu基因或者其蛋白質過度表現；主要作者、德州聖安東尼奧醫學中心的外科住院醫師Linda C. Benavides表示，對HER2基因有許多興趣，過去我們聚焦在病患，因為她們是使用Herceptin的候選人；現在我們的疫苗顯示各種HER2/neu值的病患都有反應，包括無治療的低度表現者。
她向記者表示，大部分的疫苗試驗是在轉移病患進行，但我們的結果顯示，疫苗用於最少症狀的婦女是安全的，減少了死亡率和發病率。
這項研究中最令人驚訝的是，低 HER2/neu值病患的腫瘤也對疫苗有反應；事實上，Benavides醫師指出，相較於高度表現腫瘤，低度表現病患(免疫組織化學0 - 2+) 之HER2/neu腫瘤對疫苗有比較好的反應；他們不只有較好的免疫反應，也有較好的臨床結果，接受E75胜肽疫苗之後，乳癌復發率降低且死亡率為零。
研究者之前對結節陽性和陰性乳癌病患主導了HER2/neu E75 胜肽疫苗之臨床試驗，以顯現各種的HER2/neu 值；該研究中，他們進行次組分析回顧，回顧E75疫苗試驗中163名病患的HER2/neu表現值。
所有病患都進行人類白血球組織抗原(human leukocyte antigen，HLA)分類；HLA-A2+/A3+的婦女接受疫苗；HLA-A2–/A3– 婦女作為控制組；過度表現的定義是熒光原位雜交技術(fluorescence in situ hybridization，FISH)值大於2.0 且為 IHC 3+ HER2/neu 腫瘤；低度表現定義為IHC 為0 - 2+。
92名接受疫苗的病患中，29 (34%)位定義為HER2 過度表現、 56 (66%)位定義為低度表現；控制組(n =71)包括了 22 (33%) 名過度表現者和44 (67%)名低度表現者；HER2/neu 過度表現類似有關預後和治療因素，但統計上，接受疫苗的婦女有較多過度表現HER2，且為荷爾蒙接受體陰性和結節陰性(P=0.007)。
在平均30個月的追蹤期間，疫苗組和控制組的HER2/neu過度表現者之疾病復發比率類似 (18.2% vs. 13.8%)；不過，研究者指出，疫苗組病患出現疾病復發者的死亡率比控制組低了50% (25% vs. 50%)。
研究者也指出，疫苗組HER2/neu低度表現病患的復發率持續降低，復發率只有10.7%，而控制組的有18.2%；這小組顯示，不只有免疫反應，也有更低的死亡率 (0%)。
Benavides醫師表示，這表示一種新型態的HER2直接治療，因為低度表現者不適用trastuzumab，疫苗已經註冊進行第3期試驗，將聚焦在低度表現的婦女。
低度表現婦女的首次第3期試驗即將在秋天開始；Benavides醫師解釋，根據在AACR發表的資料，第3期試驗被調整，且是首次聚焦在低度表現的婦女。
美國癌症研究學會(AACR) 2008 年會：摘要2545發表於2008年4月14日。
Novel Peptide Vaccine Reduces<
By Roxanne Nelson
Medscape Medical News
A novel peptide vaccine was able to reduce the mortality rate in women with HER2/neu overexpressing breast cancer by about half, researchers report here at the American Association for Cancer Research (AACR) 2008 Annual Meeting.
"The numbers in this study are small but the concept is good," commented William N. Hait, MD, PhD, president of the AACR and senior vice president of Worldwide Hematology and Oncology Research and Development at Johnson & Johnson. "It's a good first step and we are cautiously optimistic."
HER2/neu is a source of immunologic peptides and approximately 30% of early-stage breast cancers have an amplified HER2/neu gene or overexpression of its protein product. There has been a great deal of interest in the HER2 gene, explained lead author Linda C. Benavides, MD, a general surgical resident at Brooke Army Medical Center in San Antonio, Texas. "Historically, we have focused on patients because they are candidates for Herceptin. Our vaccine showed a response in patients who expressed HER2/neu at all levels, including low expressers for whom no therapy is available."
"Most vaccine trials have been performed in the metastatic setting," she told journalists, "But our results show that the vaccine is safe in women with minimum symptoms. It decreased mortality and morbidity."
What was most surprising in this study was that patients with low-HER2/neu-expressing tumors responded so well to the vaccine. In fact, Dr. Benavides pointed out, the patients with low-expressing (0 to 2+ on immunohistochemistry ) HER2/neu tumors had a better response to the vaccine than women with higher-expressing tumors. They experienced not only a better immune response, but a better clinical one as well, as demonstrated by a decreased rate of breast cancer recurrence and 0% mortality after E75 peptide vaccination.
The researchers had previously conducted clinical trials with the HER2/neu E75 peptide vaccine in both node-positive and node-negative breast cancer patients who demonstrated a variety of levels of HER2/neu expression. In this study, they performed a subset analysis review that was based on the level of HER2/neu expression in the 163 patients who were enrolled in their E75 vaccine trial.
All patients were typed for human leukocyte antigen (HLA). Women who were HLA-A2+/A3+ received the vaccine; women who were HLA-A2–/A3– served as the control group. Overexpression was defined as fluorescence in situ hybridization (FISH) greater than 2.0 and IHC 3+ HER2/neu tumors; low expression was defined as IHC ranging from 0 to 2+.
Of the 92 vaccinated patients, 29 (34%) were defined as HER2 overexpressors and 56 (66%) were defined as low-expressors. The control group (n = 71) included 22 (33%) overexpressors and 44 (67%) low-expressors. The HER2/neu overexpressors were similar in regard to prognostic and treatment factors, although a statistically larger number of vaccinated women who overexpressed HER2 were also hormone-receptor negative and node negative (P = 0.007).
At a median follow-up of 30 months, the rates of disease recurrence were similar between HER2/neu overexpressors in both the vaccine and control groups (18.2% vs 13.8%). However, the researchers noted that the mortality rate was 50% lower among the vaccinated patients who had a disease recurrence (25% vs 50%).
The researchers also noted that recurrence rates were substantially reduced in vaccinated patients with low HER2/neu expression. They experienced a 10.7% recurrence rate, compared with the 18.2% seen in the control group. This subgroup showed not only a better immunologic response, but also a better mortality rate (0%).
"This may represent a new form of HER2-directed therapy, because the low expressors do not qualify for trastuzumab," Dr. Benavides said. "The vaccine has been registered for a phase 3 trial, which will focus on low-expressing women."
The first phase 3 trial in low-expressing women is slated to begin in the fall. Based on the data presented at AACR, the phase 3 trial has been restructured and is the first to focus on low-expressing women, explained Dr. Benavides.
American Association for Cancer Research (AACR) 2008 Annual Meeting: Abstract 2545. Presented April 14, 2008.