In women with advanced (or metastatic) breast cancer, treatment with the breast cancer drug trastuzumab (Herceptin) is associated with prolonged survival but also increases the risk of developing heart problems, a new systematic review shows. However, the review concludes that more women benefit from the use of trastuzumab than are harmed.
The review, published in The Cochrane Library (2014; doi:10.1002/14651858.CD006242.pub2), focuses on treatment for women with advanced-stage, HER2-positive breast cancer. About one in five women with breast cancer are HER2-positive. HER2 is a protein on the surface of breast cells called human epidermal growth factor receptor 2, which encourages tumor cells to grow and divide. The prognosis for HER2-positive patients is usually worse because the high levels of HER2 on their tumor cells makes their cancer more aggressive.
The antibody-based drug trastuzumab is designed to target these specific types of tumors. It has been recommended for treating women who have 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 a total of 1,497 HER2-positive women with metastatic breast cancer, meaning their cancer could be treated but not cured. The women were given trastuzumab in combination with other drugs, either as a first-line treatment or later therapy, when their cancer had progressed.
Overall survival rates two years after starting the trials were higher for women who were given trastuzumab compared with those on regimens that did not include the drug. Women taking trastuzumab also gained another two to eleven months without further progression of their cancers. The drug was most effective when it was used as a first-line treatment or in combination with the chemotherapy drug class called taxanes.
“This review suggests that, for women with advanced breast cancer, trastuzumab has been linked to significant life expectancy gains,” said Lorenzo Moja, MD, from the Department of Biomedical Sciences for Health at the University of Milan in 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.”
However, the drug led to an increased risk for heart failure. With standard therapies, the equivalent of 300 in every 1,000 women survived at two years and only 10 developed heart problems. When trastuzumab was added, 373 survived, but 35 developed heart problems that required immediate discontinuation of trastuzumab. These cardiac dysfunctions were usually reversible after treatment stopped.
The review highlighted one particular drug combination associated with a higher risk of heart problems. “Some of the earlier trials combined trastuzumab with a class of drugs called anthracyclines,” said co-author Roberto D’Amico, PhD, director of the Italian Cochrane Centre, University of Modena and Reggio Emilia, Italy. “This combination is not recommended in patients with metastatic breast cancer.”
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