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Study Shows Combination Therapy Promising for HER-2-Positive Metastatic Breast Cancer

Study Shows Combination Therapy Promising for HER-2-Positive Metastatic Breast Cancer
Blood Test Used in Study May One Day Predict Patient's Response to Therapy
M. D. Anderson News Release 04/01/02

While studying the effectiveness of a combination chemotherapy for women with metastatic breast cancer that overexpresses the HER-2 protein, researchers at The University of Texas M. D. Anderson 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 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 HER-2 overexpressing metastatic breast cancer. The HER-2 gene is amplified in 20 to 30 percent of invasive breast cancers.

Trastuzumab is a monoclonal antibody directed against the HER-2 protein. According to M. D. Anderson investigators, when used alone in breast cancer patients who overexpress the HER-2 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 HER-2 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 HER-2 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 HER-2 protein. According to Dr. Esteva, the HER-2 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 HER-2 ECD assay for predicting response to trastuzumab-based therapy has not been fully established, said Dr. Esteva.

In the study, the assay measuring HER-2 ECD during treatment correlated with response to treatment and predicted response more accurately than other assays currently in use. In patients with elevated serum HER-2 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 HER-2 ECD concentrations at baseline. 

Using other HER-2 testing methods, 63 percent of patients testing positive for HER-2 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 the HER-2 is one of the first genetic changes associated with new drug targets for breast cancer. Many patients who overexpress HER-2 are resistant to a variety of chemotherapy agents, and as a result have a shorter life span. Therefore, if the gene amplification or protein overexpression is found early, the first line of treatment can be a HER-2 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 HER-2 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."


© 2015 The University of Texas MD Anderson Cancer Center