Novel Immunotherapy Vaccine Decreases Recurrence in HER2 Positive Breast Cancer Patients
A new breast cancer vaccine candidate, (GP2), provides further evidence of the potential of immunotherapy in preventing disease recurrence. This is especially the case for high-risk patients when it is combined with a powerful immunotherapy drug. These findings are being presented by The University of Texas MD Anderson Cancer Center at the 2014 American Society of Clinical Oncology’s Breast Cancer Symposium in San Francisco.
One of only a few vaccines of its kind in development, GP2 has been shown to be safe and effective for breast cancer patients, reducing recurrence rates by 57%. Further, women with the highest overexpression of HER2 (known as HER2 +3) had no cancer recurrences when they were administered the vaccine after completing trastuzumab (Herceptin), a type of immunotherapy drug known as a monoclonal antibody. HER2 is an oncoprotein that promotes tumor growth and is expressed to some extent in 75-80% of breast cancers.
“This is an important and different avenue in immunotherapy research, in that we are investigating ways to prevent cancer recurrence by stimulating the immune system to treat cancer,” says principal investigator Elizabeth Mittendorf, M.D., Ph.D., associate professor of Surgical Oncology. “The ultimate goal is to develop a preventative tool that will minimize the risk of recurrence in women who have already had breast cancer and for whom standard therapies have failed.”
The findings are the result of a phase II randomized trial that paired the GP2 vaccine, designed to stimulate the CD8+ cells, commonly known as “killer” or “toxic” T cells, with an immune stimulant known as granulocyte/macrophage colony stimulating factor (GM-CSF). The trial included 190 patients with varying levels of HER2; 89 women received the GP2 vaccine with a GM-CSF adjuvant and a control group of 91 patients received GM-CSF alone. Eight patients experienced early recurrence or developed a second malignancy and did not complete the vaccine trial. The vaccine is injected subcutaneously and the initial series consisted of monthly inoculations for six months, followed by four cycles of booster shots administered every six months thereafter. The patients were monitored for nearly three years.
For all 190 patients, including those who did not complete the trial, the disease-free survival (DFS) rate was 88% among those who received the vaccine and 81% in the control group - representing a 37% reduction in recurrence. Excluding the patients who did not complete the vaccine series, the results are higher - 94% DFS rate versus 85% who did not get GP2 - a 57% risk reduction.
HER2-positive breast cancer: What is it?
HER2-positive breast cancer is a breast cancer that tests positive for a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth of cancer cells. In about 1 of every 5 breast cancers, the cancer cells make an excess of HER2 due to a gene mutation. This gene mutation and the elevated levels of HER2 that it causes can occur in many types of cancer — not only breast cancer. This is a gene mutation that occurs only in the cancer cells and is not a type of mutation that you can inherit from a parent.
HER2-positive breast cancers tend to be more aggressive than other types of breast cancer. They’re also less responsive to hormone treatment. However, treatments that specifically target HER2 are very effective. They include:
Trastuzumab (Herceptin). Trastuzumab, which specifically targets HER2, kills these cancer cells and decreases the risk of recurrence. Trastuzumab is often used with chemotherapy. But it may also be used alone or in combination with hormone-blocking medications, such as an aromatase inhibitor or tamoxifen. Trastuzumab is usually well tolerated, but it does have some potential side effects, such as congestive heart failure and allergic reaction.
Lapatinib (Tykerb). Like trastuzumab, lapatinib is a HER2-specific drug. Lapatinib may be effective for HER2-positive breast cancer that doesn’t respond to trastuzumab. Lapatinib is used in combination with the chemotherapy drug capecitabine (Xeloda) and the aromatase inhibitor letrozole (Femara). Lapatinib is also being studied in combination with trastuzumab. Common side effects include rash, loose stools and the potential risk of congestive heart failure.
In addition, there are several new medications being developed that also target HER2 and are being tested in clinical trials.
Standard chemotherapy agents such as doxorubicin (Adriamycin) also can be effective in treating HER2-positive breast cancers, although these drugs don’t specifically target the HER2 protein.
Routine testing for HER2 is recommended for most women diagnosed with invasive breast cancer because the results may affect treatment recommendations and decisions. HER2 testing is not done routinely for ductal carcinoma in situ but may be performed as part of a clinical trial. Whenever breast cancer recurs or spreads, the cancer cells should be retested for HER2 as well as for hormone receptor status, as these can change from the original cancer in up to 20 to 30 percent of cases.
Women with HER2 +3 who were administered trastuzumab as part of the standard of care prior to receiving the vaccine experienced no cases of cancer recurrence. According to Mittendorf, trastuzumab may act like a primer for the vaccine. Trastuzumab stimulates CD4+ T cells to release substances that fight cancer cells and initiates an antibody response. Thus, it may prepare the immune system, making the vaccine even more effective. MD Anderson is now testing this combination of immunotherapies in other clinical trials.
Personalized Immunotherapy
The GP2 study supports previous MD Anderson research on similar breast cancer vaccines, such as AE37, which showed a significant immune response and improved recurrence rates in triple-negative breast cancer patients. Another candidate, E75, known as NeuVax or nelipepimut-S, showed a 50% recurrence decrease in high-risk patients. Currently, NeuVax is being tested internationally in a phase III clinical trial.
Genes and Breast Cancer
Breast cancer is often discussed as a general condition, but there are several different types that require different treatments.
One way to distinguish breast cancer cells is through your genes. When you’re diagnosed with breast cancer, your doctor will test the cancerous cells to determine their genetic makeup.
Click through the slideshow to learn what it means if the genes in your cancer cells have more HER2 protein than they should.
HER2 Basics
HER2 is a protein that stimulates the growth of breast cancer cells. It can be found in your blood and urine. Sometimes it’s referred to as a “tumor marker.”
Tumor markers like HER2 can’t be used for cancer diagnosis. But, they can provide other important information. For example, the presence of HER2 can help your doctor predict how your breast cancer is likely to respond to treatment.
How Many are HER2-Positive?
The Mayo Clinic estimates that about 20 percent of breast cancers are HER2-positive. Younger women are more likely to be HER2-positive than older women, the University of Maryland Medical Center (UMMC) notes.
HER2-positive breast cancer tends to be more aggressive and to spread more quickly than other cancers. That’s why it’s important to find out if the cancer cells in your body contain this protein.
Testing for HER2
Your doctor will order a lab test to determine if your cancer is HER2-positive. The American Cancer Society (ACS) advises that all patients diagnosed with breast cancer should get tested for HER2.
If your breast cancer is HER2-positive, you have a much better chance of successful treatment with methods that target the HER2 protein specifically.
“We believe many more patients will benefit in some way from immunotherapy,” says Mittendorf. “The challenge will be identifying the right immunotherapeutic approach for each individual patient. When doctors are able to do that, cancer therapy, and immunotherapy specifically, will follow a more personalized approach.”
Other researchers contributing to the study include: Jennifer Litton, M.D.; James Murray, M.D., MPH; Guy Clifton, M.D. from MD Anderson; John Berry, M.D., Nathan Shumway, M.D., Timothy Vreeland, M.D., George Peoples, M.D., Erika Schneble, M.D., Julia Greene, M.D. and Alfred Trappey, M.D. from Brooke Army Medical Center; Sathibalan Ponniah, Ph.D. from Uniformed Services University of the Health Sciences; Alexandros Ardavanis, M.D., Michael Papamichail, M.D. and Sonia Perez, M.D. from Saint Savvas Cancer Hospital in Athens, Greece.
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