A vaccine based on an immunogenic peptide from the HER2/neu protein (E75) significantly reduces the risk of recurrence and death in women treated for HER2/neu-positive breast cancer, according to new data. "by Megan Rauscher

A vaccine based on an immunogenic peptide from the HER2/neu protein (E75) significantly reduces the risk of recurrence and death in women treated for HER2/neu-positive breast cancer, according to data reported Sunday at the American Association for Cancer Research 2008 annual meeting underway in San Diego.

The vaccine has shown positive results "in patients with all levels of HER2/neu expression," Dr. Linda C. Benavides, of Brook Army Medical Center in San Antonio, Texas, told the conference. "But what was very surprising to us was that the best effect has been in the HER2/neu low-expressing patients, which make up approximately 50 per cent of all breast cancer patients and represent a group of women who do not currently qualify for trastuzumab (Herceptin) therapy."

Dr. Benavides and colleagues performed a subset analysis based on the levels of HER2/neu expression in 163 women with node-positive and high-risk node-negative breast cancer enrolled in a phase II trial of the E75 vaccine in the adjuvant setting.

Following successful standard multimodality therapy (surgery, chemotherapy, radiation), 92 women received the E75 vaccine and 71 did not (controls). The vaccine was given intradermally every three to four weeks for a total of six inoculations.

Following vaccination, immunologic responses were similar between HER2/neu low- and over-expressing patients; however, patients in the vaccination arm who were HER2/neu low-expressers demonstrated an increased number of E75-specific CD8+ T cells, when compared with the HER2/neu over-expressers.

At a median follow up of 30 months, recurrence rates were similar (18.2 per cent) in both HER2/neu over-expressers and HER2/neu low-expressers in the unvaccinated control group. Among the E75-vaccinated women, the recurrence rate decreased to 10.7 per cent in the low-expressing women and 13.8 per cent in the over-expressing E75-vaccinated women, Dr. Benavides reported.

"Most importantly," she said, "the mortality rates were decreased in both HER2/neu low-expressing and over-expressing women."

Specifically, the mortality rate in the HER2/neu over-expressing women was 9.1 per cent in the control group compared with 3.4 per cent in the vaccinated group; among HER2/neu low-expressing women, the mortality rate was 6.8 per cent in the control group compared with zero per cent in the vaccine group.

"In addition, there appeared to be a vaccine effect, even among patients who did recur," Dr. Benavides said. "For the over-expressers, the risk of mortality in the control group among those who recurred was 50 per cent compared to 25 per cent in the vaccinated group. For the low-expressers, the risk of mortality in the control group among those patients who recurred was 38 per cent compared to zero per cent in the vaccinated patients."

She pointed out in a statement that the findings underscore "the difference in mechanism between the vaccine vs. antibody therapy like trastuzumab."

Based on these results, phase III E75-peptide vaccine trials, set to get underway this fall, will focus exclusively on HER2/neu low-expressing women, with subsequent trials performed in HER2/neu over-expressing women following trastuzumab therapy, Dr. Benavides noted.

"The E75 vaccine, if validated in phase III testing, may represent a new form of HER2/neu-directed therapy, which could be utilized in the HER2/neu low-expressing group of breast cancer patients."


Source: Reuters"

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