Herceptin - new hope for women with advanced breast cancer

by Alice A. Buckley

All women with advanced breast cancer 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. But on the eve of October's National Breast Cancer Awareness Month, FDA approved a new drug called Herceptin that attacks a particularly aggressive form of breast cancer in a completely new way. As many as 60,000 women have this aggressive form of the disease, which usually follows a quick and deadly course. What promise does Herceptin hold for one of the most deadly forms of breast cancer?

Until last month, Margaret, a 59-year old woman with advanced breast cancer, had exhausted all of the available standard medical treatmentsfor her disease. She felt experimental and alternative therapies were her only remaining options. But late last month, the U.S Food and Drug Administration (FDA) approved a powerful new medicine - Herceptin - to treat Margaret's breast cancer.

Margaret has a type of breast cancer that affects approximately 30% of the 180,000 women who are diagnosed with breast cancer each year. Her cancer is characterized by an overabundance of a protein known as human epithelial growth factor receptor-2 (HER-2), which stimulates the growth of breast tumors. One particular molecule on HER-2, the HER-2 receptor, causes breast cancer cells to grow aggressively and quickly. Herceptin, known as a monoclonal antibody, latches onto the HER-2 receptor, blocks its activity, and inhibits the growth of malignant cancer cells by eventually causing their death.

Since 1986, scientists have known that women whose breast cancers produce too muchHER-2 have cancers that are more ferocious and are more likely to metastasize, or spread. However, Herceptin can enhance the effectiveness of standard chemotherapy treatmentsin women like Margaret by targeting the HER-2 receptor and inhibiting its activity.

The FDA approval marks the end of a lottery system created in August 1995 by the National Cancer Institute (NCI) and Genentech, Inc., the company that manufactures Herceptin. The supply of Herceptin was so limited before its FDA approval that only some of the women eligible for treatment could receive it. Beginning this month, however, NCI and Genentech promise an adequate supply of Herceptin for all women who need it.

"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 receiving Herceptin and chemotherapy had slower cancer growth and responded better to treatment than women who didn't receive 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 in May when the results of his Herceptin 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 do not respond to any new treatments, about 14% responded to the drug for an average of about nine months.

After its approval by the FDA, 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 cardiomyopathy, 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, FDA recommends that every woman considering Herceptin have a thorough cardiac assessment before taking the drug.

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, Herceptin can exacerbate some other side effects of chemotherapy, including anemia, diarrhea, abdominal pain, and infection.

It is important to remember that Herceptin is approved for use only in women with breast cancer that overproduces HER-2 and is so advanced that it has spread to other parts of the body. At this point, there are no data available indicating that Herceptin is effective on less-advanced breast cancers. Research continues to try to answer this question and to study the use of Herceptin in other cancers, such as ovarian cancer.

To help doctors determine if a breast tumor is producing an excess of HER-2, FDA also approved a new diagnostic test which measures HER-2 levels in tumors. The DAKO HerceptTest will help determine which women will benefit from Herceptin treatment.