Benefits of trastuzumab outweigh the risk of harm in advanced breast cancer

A new systematic review shows that treatment with the breast cancer drug trastuzumab (Herceptin) is associated with prolonged survival in women with advanced (metastatic) breast cancer, but the risk of developing heart problems also increases. The review concludes that more women benefit from use of trastuzumab than are harmed.

The Cochrane review focused on treatment for women with advanced stage breast cancer who have tested HER2-positive. Human epidermal growth factor receptor 2 (HER2) is a protein on the surface of breast cells that encourages tumor cells to grow and divide. About 1 in 5 women with breast cancer are HER2-positive. The prognosis for HER2-positive patients is usually worse because the high levels of HER2 on the tumor cells make the cancer more aggressive.

Trastuzumab is a targeted biological drug (a monoclonal antibody) that attaches to the HER2 protein, blocking the growth of malignant cells. It has been used for the treatment of HER2-positive advanced breast cancer since 1998 in the United States and 2002 in the United Kingdom.

The authors reviewed data from seven trials involving 1,497 women with HER2-positive metastatic breast cancer. The women were treated with trastuzumab in combination with other drugs as either a first-line treatment or after their cancer had progressed.

Two years after starting the trials, overall survival rates were higher for women who received trastuzumab than for those on regimens that did not include the drug. Women taking trastuzumab gained 2 to 11 months without progression of their cancers. The drug was most effective when used as a first-line treatment or in combination with the chemotherapy drug class called taxanes.

Five studies showed that Trastuzumab extended time to death by 5 to 8 months.

“This review suggests that, for women with advanced breast cancer, trastuzumab has been linked to significant life expectancy gains," said Lorenzo Moja, MD, of the Department of Biomedical Sciences for Health at the University of Milan in Milan, Italy and one of the authors of the review. "We found that women survived longer and their cancer did not progress as quickly when they received trastuzumab (Herceptin).”

Although trastuzumab did not raise the risk of neutropenic fever or anemia, it seemed to increase the risk of neutropenia.

However, the drug led to an increased risk of congestive heart failure and decline in the left ventricular ejection fraction. With standard therapies, 300 out of every 1,000 women would survive at 2 years and 10 would develop heart problems. With the addition of trastuzumab, 373 women would survive, but 35 would develop severe heart problems. The cardiac toxicity is usually reversible if trastuzumab is discontinued immediately.

This study was published in The Cochrane Library (doi:10.1002/14651858.CD006242.pub2).


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