According to a recent article published in Oncology Reports, administration of Herceptin® (trastuzumab) into the central nervous system (CNS) may help to slow disease progression in patients with breast cancer whose cancer has spread to the CNS.
A significant portion of women diagnosed with breast cancer have what is called HER2-positive breast cancer. Patients with HER2-positive breast cancer have cancer that has one or more mutations (genetic alteration) within the human epidermal growth factor receptor-2 (HER-2) pathway.
Mutations within the HER-2 result in overproduction of the HER2 receptor, which is found on the outside of cancer cells. Patients who have an excess amount of these receptors are referred to as HER2-positive.
All women with breast cancer should undergo testing to determine if their cancer is HER2-positive.
Herceptin is a monoclonal antibody (protein) that is targeted against HER2. It binds to the receptors, which stops them from stimulating the spread of cancer cells that overexpress HER2. Herceptin is currently approved for the treatment of HER2-postivive, metastatic breast cancer in combination with the chemotherapy agent Taxol® (paclitaxel, or as a single agent in women whose breast cancer has recurred following previous therapy.
Herceptin does not enter the blood-brain barrier when it is administered intravenously (into a vein). The blood-brain barrier is a highly selective membrane that surrounds the brain and spinal cord (CNS). In order to protect the brain and spinal cord from harmful substances, this barrier allows only very specific molecules to pass through.
As a result, while Herceptin and improved chemotherapy regimens have reduced cancer progression in the rest of the body, women with breast cancer are now experiencing cancer progression in the CNS.
Researchers from Germany recently treated a patient with breast cancer with Herceptin that was administered intrathecally (into the spinal column). The woman was 39 years and had HER2-positive, metastatic breast cancer. She had cancer spread to one site in the brain, which was surgically removed. She then received the chemotherapy agent Xeloda® (capecitabine) plus intravenous Herceptin.
When her condition worsened, she was treated intrathecally with the chemotherapy agent methotrexate. Her condition continued to deteriorate, so her physicians administered Herceptin intrathecally. Within two weeks of therapy, she had improved significantly. Furthermore, clinical symptoms and results from magnetic resonance imaging (MRI) showed that her cancer did not progress for 11 months following diagnosis of CNS spread. Intrathecal administration with Herceptin was very well tolerated.
The researchers concluded that, although this case report included only one patient, intrathecal administration of Herceptin may provide substantial improvements in slowing disease progression that has spread to the CNS among HER2-positive breast cancer patients.
Although this approach still needs to be tested extensively in clinical trials, these results are promising. In the future, intrathecal administration of Herceptin may be used to prevent of spread to the CNS among women with HER2-positive breast cancer.
Reference: Stemmler H, Schmitt M, Harbeck N, et al. Applicatin of Intrathecal Trastuzumab (Herceptin®) for Treatment of Meningeal Carcinomatosis in HER2-overexpressing Metastatic Breast Cancer. Oncology Reports. 2006; 15:1373-1377.
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