All women with advanced
face a difficult and uncertain future. Most of them endure long courses of medical treatment that leave them looking to alternative or experimental therapies for a cure. As many as 60,000 women have an aggressive form of the disease, which usually follows a quick and deadly course. A drug called
attacks a particularly aggressive form of breast cancer in a novel way. What promise does Herceptin hold for one of the most deadly forms of breast cancer?
That question was answered in part by Dr. Gabriel Hortobagyi. The Doctor wrote in an October 20, 2005 editorial in the
New England Journal of Medicine
that the latest results of Herceptin trials “are not evolutionary but revolutionary.”
Advanced breast cancer affects approximately 30% of the 180,000 women who are diagnosed with breast cancer each year. The more aggressive form is characterized by an overabundance of a protein known as human epithelial growth factor receptor-2 (HER-2). This protein stimulates the growth of breast tumors.
Herceptin (trastuzumab), is a monoclonal antibody which blocks the HER-2 receptor. This inhibits the growth of malignant cancer cells by eventually causing their death.
Since 1986, scientists have known that women whose breast cancers produce too much HER-2 have cancers that are more aggressive and are more likely to metastasize, or spread. Herceptin can enhance the effectiveness of standard
treatments by targeting the HER-2 receptor and inhibiting its activity.
Herceptin Delays Cancer Progression
"We have a new agent that is effective," said Dr. Dennis Slamon, vice-chair of research at the University of California at Los Angeles, and one of the primary researchers behind Herceptin. Two of his research trials provided information that helped Herceptin get approved less than five months after submission to FDA.
Slamon's first study showed that nearly half of all women with Her-2/neu positive tumors receiving Herceptin and chemotherapy had slower cancer growth and responded better to treatment than women who didn't receive the Herceptin. Perhaps most encouraging was the news that the women who received Herceptin also had better one-year survival rates.
"The addition of Herceptin made a significant increase in all of the parameters we looked at," Dr. Slamon commented when the results of his trials were first made public. After one year of treatment, cancer growth was halted in 28% of women treated with Herceptin plus chemotherapy, compared with 14% receiving just chemotherapy.
Another study showed that the use of Herceptin alone could benefit some seriously ill women whose previous chemotherapy treatments had failed. In these patients, who usually did not respond to any new treatments, about 14% responded to the drug for an average of about nine months.
Studies published in 2007 showed that Herceptin significantly decreased tumor recurrence in women with Her-2 receptors, whether or not they had “positive” metastatic lymph nodes at the time of treatment. These findings potentially extend the usefulness of Herceptin to all women with Her-2 receptors in their tumors, regardless of whether or not their tumors are advanced. It is important to note that Herceptin does not improve outcomes for women with cancers not expressing Her-2 receptors.
Mixed Side Effects
After its approval by the FDA, then Health and Human Services Secretary Donna E. Shalala summarized Herceptin's promise, "For certain women with advanced disease, this new product can mean new hope."
But Herceptin is not without side effects. Up to 28% of all women taking the drug with chemotherapy agents experienced heart problems, including
This is a potentially life-threatening heart muscle weakness that can lead to
congestive heart failure
. This side effect is particularly common in women receiving chemotherapy with drugs known as anthracyclines (including a common breast cancer therapy called doxorubicin) and cyclophosphamide.
For this reason, the FDA recommends that every woman considering Herceptin have a thorough cardiac assessment before taking the drug and during Herceptin treatment. Recent data suggests, however, that the risk of permanent heart damage is fairly low and likely does not exceed 4% of women receiving the drug. In most cases, the benefits of Herceptin—when indicated—greatly outweigh the risks.
When first administered, Herceptin can also produce mild chills, fever, pain, weakness, nausea, vomiting, and headache in up to half of all women. But these side effects are much less likely to recur with each new dose, a significant improvement over most cancer-fighting treatments. Also, the side effects commonly seen with standard chemotherapy—including hair loss, mouth sores, and bone marrow suppression—are rare with Herceptin. However, the treatment can exacerbate some other side effects of chemotherapy, including
, and infection.
Other Potential Applications
It is important to remember that Herceptin, since its approval in 1998 by FDA, has been used only in women with breast cancer that overproduces HER-2 and is so advanced that it has spread to other parts of the body. Recently, the FDA has expanded its use for women with less advanced disease in combination with other cancer drugs for the treatment of HER-2 positive breast cancer after surgery (
Preclinical and early clinical studies have shown that the efficacy of Herceptin is greatly enhanced when combined with chemotherapy.
These findings led to clinical studies involving patients with HER-2/neu overexpressing breast cancer. These patients, who had not previously been treated with chemotherapy for metastatic disease, were given either Herceptin combined with doxorubicin/epirubicin and cyclophosphamide (if they had no previous chemotherapy with these drugs) or with a class of drugs called taxanes (if the patients had received doxorubicin/epirubicin previously). The combination of Herceptin with chemotherapy improved objective response rates and significantly prolonged time to disease progression, duration of response, and survival as compared with treatment with chemotherapy alone.
Research continues to try to determine the best way to use Herceptin as well as to study the use of Herceptin in other cancers, such as
and nonsmall cell
. A diagnostic test that measures HER-2 levels in tumors can help doctors determine if a breast tumor is producing an excess of HER-2. Several FDA-approved commercial assays are available to aid in the selection of patients for Herceptin therapy. These include Dako's HercepTest™ (IHC assays) and Abbott's PathVysion® (FISH assays).
These tests will help determine which women will benefit from Herceptin treatment.
Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer.
N Engl J Med.
Slamon DJ, Leyland-Jones B, Shak S, et al. Concurrent administration of anti-HER2 monoclonal antibody and first-line chemotherapy for HER2-overexpressing metastatic breast cancer: A phase III, multinational, randomized, controlled trial.
N Engl J Med.
Please be aware that this information is provided to supplement the care
provided by your physician. It is neither intended nor implied to be a
substitute for professional medical advice. CALL YOUR HEALTHCARE PROVIDER
IMMEDIATELY IF YOU THINK YOU MAY HAVE A MEDICAL EMERGENCY. Always seek the
advice of your physician or other qualified health provider prior to
starting any new treatment or with any questions you may have regarding a