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, published in The
Cochrane Library, concludes that more women benefit from use of Trastuzumab
than are harmed.
The review focuses on treatment for women with advanced
stage breast cancer who have tested HER2- positive. About 1 in 5 women with
breast cancer are HER2-positive. HER2 is a protein on the surface of breast
cells called human epidermal growth factor receptor 2. It encourages tumour
cells to grow and divide. The prognosis for HER2-positive patients is usually
worse because the high levels of HER2 on their tumour cells make their cancer
The antibody-based drug Trastuzumab is designed to target
these specific types of tumours. It has been recommended for treating women who
have HER2-positive advanced breast cancer since 1998 in the US and 2002 in the
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 than for those on regimens
that did not include the drug. Women on 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 (Herceptin®) has been linked to significant life expectancy
gains," said Lorenzo Moja, one of the authors of the review, based at the
Department of Biomedical Sciences for Health at the University of Milan in
Milan, Italy. "We found that women survived longer and their cancer did
not progress as quickly when they received Trastuzumab (Herceptin®)."
However, the drug led to an increased risk of 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 (Herceptin®)
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 (Herceptin®) with a class of drugs called anthracyclines,"
said Roberto D'Amico, director of the Italian Cochrane Centre, University of
Modena and Reggio Emilia, Italy and co-author of the review. "This combination
is not recommended in patients with metastatic breast cancer."
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