SAN ANTONIO, Texas (Army News Service, Dec. 21, 2006) - An Army-led breast cancer vaccination study offers hope to breast cancer survivors. Early study results suggest a 50 percent reduction in disease recurrence for vaccinated women.

Dr. (Col.) George Peoples, a Brooke Army Medical Center surgeon and principal investigator for the study, released the results of the six-year study Dec. 14 at the San Antonio Breast Cancer Symposium here.

While still in the early stages of testing, the results of the study, the doctor said, are "intriguing."

The vaccine targets HER2/neu, a protein that plays a role in cell growth. In larger amounts, the protein accelerates tumor growth and, as a result, can lead to a poorer prognosis for women with breast cancer.

The researchers' goal was to create a vaccine that boosted the body's immune system so it could recognize and battle the protein before it stimulates growth.

"We took the HER2/neu protein, broke it down into basic pieces so we could find the piece, called a peptide, which the immune system could recognize," Peoples said.

"If the body can recognize the protein bit, which is potentially dangerous, then the immune system has a chance to rev up before an intact tumor cell is present," Peoples explained. "It's much tougher for the immune system to fight when overwhelmed with an established cancer, which expresses a multitude of proteins."

The use of a single peptide is a simplistic one to scientists, who believe more sophisticated vaccines are the answer, Peoples said. "No one believed a simple peptide vaccine like this would work, including me."

To achieve the desired results, researchers took a revolutionary approach to their study by administering the vaccine containing the peptide to healthy women, rather than to women with late-stage disease. "

This is one of the first times we've used a breast cancer vaccine in women who are free of the disease and with an intact immune system," Peoples said.

Previous trials have involved patients in late-stage disease, mainly because those patients were the most willing to undergo high-risk type treatments. However, "it's not fair to test vaccines in that setting," Peoples said. "It's analogous to getting your flu shot when you already have the flu.

"We want to use the vaccine for what it's meant to do; we want to prevent disease."

The study was limited to women who previously had breast cancer, but were disease-free, having completed all primary therapies, such as chemotherapy and radiation.

Researchers accepted 186 patients into the study, which took place at Walter Reed Army Medical Center in Washington, D.C., and the Joyce Murtha Breast Cancer Center in Pennsylvania.

Once they met the initial criteria for study participation, the women were tested to see if they were Human Leukocyte Antigens-A2 positive or HLA-A2 negative. HLA are proteins located on the surface of white blood cells and tissues in the body and are responsible for presenting peptides to the immune system for recognition.

The vaccine was designed to target the HLA-A2 molecule simply because it is the most common, encompassing about 50 percent of the population, Peoples said. "We chose it because if we were going to spend five or six years researching the vaccine, we wanted it to benefit the most people."

Out of the 186 study participants, 101 were A2 positive women and were vaccinated. The other 85, who were A2 negative, were followed as a control group and were able to continue whatever therapy they were on or start new therapy.

The vaccination regimen was one shot per month for six months with variations for testing purposes. In the early phase of the trial, doses were small to ensure safety; therefore, the results of this trial are even more interesting since not all women got the optimal dose of the vaccine.

"Nearly every woman formed some type of immune response to the vaccine," Peoples said. "But the most important question is, 'does that immunity mean anything''"

Early research suggests it does. Of the 186 patients, the recurrence rate as of last month was 16 percent in the control group and 8 percent for the vaccinated group - a 50 percent reduction in recurrence.

However, the study includes a low number of patients so even a single recurrence can cause the results to vacillate, he said. "We were at a statistically significant level three months ago, but because of a late recurrence in the vaccinated group, we currently are not," Peoples said. "We will have to continue to follow the patients' clinical course in order to demonstrate a statistically different recurrence rate."

However, "the results are intriguing, intriguing enough to go to the next step, especially since only one of the vaccinated patients who recurred actually received the optimal dose of the vaccine."

If the Food and Drug Administration agrees with Peoples, the next step will be Phase 3 testing, which includes multiple sites and a much larger pool of participants. But rather than the Army, the next phase will be conducted by a commercial company called Apthera.

As for the Army, the study has launched numerous other vaccine trials, including a breast cancer vaccine for HLA-A2 negative women and vaccines comprising various other peptides. The ultimate goal, Peoples said, is to reach the point where the vaccine is used as a preventive for recurrences as well as for women who never had the disease but are at increased risk for breast cancer.

"But we have to test in a systematic way," he said. "It's a lengthy process for safety reasons, but initial results are promising, and we're pressing on."