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Combination treatment may improve survival of breast cancer patients with brain metastases
Date:11/1/2012

Adding an angiogenesis inhibitor to treatment with a HER2-inhibiting drug could improve outcomes for patients with HER2-positive breast cancer who develop brain metastases. In their report published online in PNAS Plus, Massachusetts General Hospital (MGH) investigators report the first preclinical study combining antiangiogenic and anti-HER2 drugs in an animal model of brain metastatic breast cancer.

"We have shown dramatic improvement in survival by slowing the growth of brain metastatic, HER2-amplified breast cancer," says Rakesh Jain, PhD, director of the Steele Laboratory for Tumor Biology at MGH, Cook Professor of Radiation Oncology (Tumor Biology) at Harvard Medical School and senior author of the study. "This is particularly important because patients with this type of breast cancer have an increased risk of brain metastases, which have not responded to current therapies."

A quarter of breast cancers are driven by overexpression of the growth factor HER2, making them particularly aggressive. Treatment with drugs that block the pathway controlled by HER2 trastuzumab (Herceptin) and lapatinib (Tykerb) suppresses the growth of these tumors and extends patient survival. But these patients are at increased risk of developing brain metastases, which have resisted anti-HER2 treatment. Angiogenesis is also known to have an important role in breast cancer, and although previous studies combining chemotherapy with the antiangiogenesis drug bevacizumab (Avastin) delayed disease progression, they have not extended overall survival.

In addition to directly blocking the HER2-controlled growth pathway, anti-HER2 drugs also contribute to suppression of tumor-associated blood vessels. Previous studies in Jain's lab suggested that the proangiogenic factor VEGF may overcome the antiangiogenic effects of anti-HER2 drugs. This observation led the researchers to investigate whether blocking the VEGF pathway would improve the results of a
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Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
Source:Eurekalert

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