my personal edition > breast cancer > news


  E-Mail this DGNews to a colleague

DGNews

New Blood Test May Predict How HER2-Positive Breast Cancer Patients Will Respond to Herceptin (Trastuzumab)-Based Therapy

HOUSTON, TX -- April 3, 2002 -- While studying the effectiveness of a combination chemotherapy for women with metastatic breast cancer that overexpresses the HER2 protein, researchers at the University of Texas M. D. Anderson Cancer Center found that a new blood test may someday be a promising predictor for how similar patients may respond to trastuzumab (Herceptin) monoclonal antibody therapy.

In the April 1 issue of the Journal of Clinical Oncology, M. D. Anderson researchers published for the first time that trastuzumab combined with docetaxel (Taxotere) is safe and effective in treating patients with HER2 over-expressing metastatic breast cancer. The HER2 gene is amplified in 20 to 30 percent of invasive breast cancers.

Trastuzumab is a monoclonal antibody directed against the HER2 protein. According to M. D. Anderson investigators, when used alone in breast cancer patients who over-express the HER2 protein, trastuzumab produces a response rate in patients that ranges from 12 percent to 40 percent. Docetaxel is considered one of the most active chemotherapy agents when used alone in patients with metastatic breast cancer.

Of the study's 30 patients with metastatic breast cancer who also tested positive for the HER2 protein, the overall response rate was 63 percent. When patients with minor response and stable disease were considered, 83 percent of patients had some clinical benefit from the weekly regimen. None of the patients had a complete response.

The combination appears to be less toxic than other chemotherapies used alone or in combination with trastuzumab, said researchers.

"For some time, there have been preliminary data showing the effectiveness of trastuzumab and docetaxel, but this is the first time a full report has been published in a peer-reviewed journal," said Dr. Francisco J. Esteva, assistant professor in breast medical oncology and lead investigator of the study. "While this is very good news for patients who are HER2 positive, what is also exciting is the secondary finding of a possible new method for predicting response to trastuzumab-based therapy."

The method used in the published article is a blood test that can determine the extracellular domain (ECD) of the HER2 protein. According to Dr. Esteva, the HER2 ECD is shed into the blood circulation and can be elevated in patients with metastatic breast cancer. This blood test has been found to be useful in the follow-up and monitoring of patients with metastatic breast cancer. However, the clinical utility of the serum HER2 ECD assay for predicting response to trastuzumab-based therapy has not been fully established, said Dr. Esteva.

In the study, the assay measuring HER2 ECD during treatment correlated with response to treatment and predicted response more accurately than other assays currently in use. In patients with elevated serum HER2 ECD at the beginning of treatment, 76 percent showed an overall response rate to trastuzumab and docetaxel treatment compared to 33 percent in patients with low HER2 ECD concentrations at baseline.

Using other HER2 testing methods, 63 percent of patients testing positive for HER2 using the immunohistochemistry assay (IHC) showed a response while 67 percent of patients testing positive using the fluorescence in situ hybridization (FISH) showed response. FISH is currently considered the best predictor of response to trastuzumab monoclonal antibody therapy.

According to Dr. Esteva, testing for the gene or protein status is vital as HER2 is one of the first genetic changes associated with new drug targets for breast cancer. Many patients who over-express HER2 are resistant to a variety of chemotherapy agents, and as a result have a shorter life span.

Therefore, if the gene amplification or protein over-expression is found early, the first line of treatment can be a HER2-targeted weapon such as the combination therapy studied by M. D. Anderson researchers.

"We have much to do in this area, but if we can find a real-time predictor for how patients will respond to HER2-targeted therapy, we can plan treatment even better," said Dr. Esteva. "This is a classic example of how translational research works: taking a need from the clinic and developing a laboratory-based assay to move patient care forward."

SOURCE: M.D. Anderson Cancer Center

E-Mail this DGNews to a colleague

To print, use this version