They may be baby steps, but researchers at Washington University School of Medicine in St. Louis took a few more of them this week with the publication of a study looking at a potential new breast cancer vaccine.
“We’ve been working on this vaccine for many years,” said Dr. William Gillanders, a breast cancer surgeon and vice chairman for research at Washington University School of Medicine’s Department of Surgery. “It’s a very encouraging preliminary result.”
The study, just published in Clinical Cancer Research, describes the results of a phase 1 clinical trial testing the safety of the new vaccine, which targets a protein called mammaglobin-A, which is commonly overexpressed in breast cancer.
“We’re targeting a new antigen; this is the first time anybody has targeted mammaglobin-A in a vaccine trial,” Gillanders said. “One of the attractive things is that it’s overexpressed in the majority of breast cancers which suggests that many patients could be effectively treated with this vaccine.”
Gillanders said the mammaglobin-A protein is usually overexpressed in 80 percent of luminal breast cancers, which tend to be estrogen-receptor positive. In other types of breast cancer, such as triple negative, the protein is overexpressed in about 40 to 50 percent of cases.
“Luminal is based on the molecular subtype and estrogen receptor status is based on a biomarker, but they’re almost synonymous,” he said. “If you take all comers, it’s definitely the majority of breast cancers that express mammaglobin-A.”
The primary goal of the study was to determine the safety of the vaccine. Toward that end, Gillanders and his team vaccinated 14 metastatic breast cancer patients whose cancer had spread to other areas of their body (primarily their bones). Researchers closely measured the subjects’ response to the vaccine in the first six months with eight or more clinical and laboratory assessments. The patients were followed for a year.
While flu-like symptoms were reported by some patients after receiving the vaccine, the researchers observed no significant adverse effects.
What was observed, however, was an immune response in the majority of patients who received the vaccine.
“The most provocative finding is we compared patients who received the vaccine and patients who did not receive the vaccine and progression-free survival was improved,” said Gillanders. “The trial wasn’t powered for that question, but it was a statistically significant result.”
Not yet ready for prime time
Dr. Lupe Salazar, a breast cancer researcher and oncologist at Fred Hutchinson Cancer Research Center and its treatment arm, Seattle Cancer Care Alliance, said the results are encouraging but cautioned they are still very preliminary.
“It’s promising but it’s not prime time yet,” she said. “It definitely warrants additional testing and a larger study. The sample size of 14 patients was very tiny.”
A member of the Fred Hutch, SCCA and University of Washington-driven Tumor Vaccine Group, Salazar works with breast cancer vaccine pioneer Dr. Nora Disis, a UW-based expert in breast and ovarian cancer immunology. Disis presented findings at the annual meeting of the American Society of Clinical Oncology in June regarding a DNA vaccine that targeted HER2, another protein that is overexpressed in certain types of breast cancer.
“It’s a tumor antigen, just like mammaglobin-A,” Salazar said. “We’ve done a study with DNA vaccines that showed that in 66 patients, the majority of test subjects develop very nice, robust T-cell immune responses to the vaccination. And it’s also not toxic.”
Salazar said breast cancer vaccines are a hot-ticket item right now and are being studied at many research institutions across the country. The Seattle-based Tumor Vaccine Group, established in 1993, is currently recruiting for new breast cancer vaccine trials and is actively developing a multi-antigen vaccine that will target some of the most common tumor types.
“Really, the next step is to do a DNA vaccine that targets multiple tumor antigens, and that’s where we’re going next,” she said.
“Our group started with HER2 but we know we have to target multiple tumor antigens that are expressed in large numbers by breast cancer. When you target only one protein at a time, you’re limiting your ability to vaccinate a large number of patients. Not everybody is HER2 positive and not everybody is mammaglobin-A positive. If you’re going to be using a vaccine worldwide, you want to make it a vaccine that doesn’t rely on you testing for this and this and this. You want to make it applicable to as many people as possible.”
Next steps: testing how well the vaccine works
Gillanders said the next step for his research team will be another trial to test the efficacy of the vaccine, especially with regard to patients with early stage disease.
He plans to test the vaccine on newly diagnosed breast cancer patients who are receiving neoadjuvant endocrine therapy — typically an aromatase inhibitor — to shrink their tumors prior to surgery. “Then when we do the surgery, we’ll harvest the tumor and see the immune response in it, and that will provide more insight into how effective this vaccine is,” he said.
By targeting patients with early stage disease, Gillanders hopes to get a better understanding of the efficacy of the vaccine, which may not be as pronounced in metastatic patients due to the progression of their disease.
“Measuring the immune response in the tumor will be a much better surrogate for whether or not the vaccine is effective,” he said.
Ultimately, he said his goal is to not only come up with a vaccine that can be used to treat breast cancer but to prevent the disease.
Breast cancer survivors and others shouldn’t start rolling up their sleeves just yet, though. Even with good results, Gillanders cautioned that a vaccine could still be years away.
“For most drugs, it’s eight to 10 years from phase 1 to market approval,” he said, adding that the preliminary work presented this week was the result of 10 years of research.
“This is the result of a very long road,” he said.
Diane Mapes is a staff writer at Fred Hutchinson Cancer Research Center. She has written extensively about health issues for NBC News, TODAY, CNN, MSN, Seattle Magazine and other publications. A breast cancer survivor, she also writes the breast cancer blog doublewhammied.com. Reach her at email@example.com.
Solid tumors, such as those of the breast, are the focus of Solid Tumor Translational Research, a network comprised of Fred Hutchinson Cancer Research Center, UW Medicine and Seattle Cancer Care Alliance. STTR is bridging laboratory sciences and patient care to provide the most precise treatment options for patients with solid tumor cancers.
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