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Bevacizumab and breast cancer: what does the future hold?

ABSTRACT: Breast cancer is a major health concern for many women, but despite the current standard therapies, many women still die of metastatic disease. Angiogenesis has been evaluated as a possible target for therapy and bevacizumab (Avastin(®), Genentech/Roche, CA, USA), a monoclonal antibody against VEGF-A, has been developed to target this. Current clinical trials utilizing bevacizumab have shown an increase in progression-free survival, but this has not translated to an increase in overall survival in breast cancer patients. In this article, we summarize the currently published trials utilizing bevacizumab in the treatment of breast cancer and describe various methods of measuring angiogenesis in vitro and in vivo. We also describe the related process of lymphangiogenesis, as this may contribute to the mechanism of cancer progression and may be a potential target for therapy in the future. Understanding these processes may help us develop new treatments for breast cancer.

SUBMITTER: Stevenson CE

PROVIDER: S-EPMC3464486 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Bevacizumab and breast cancer: what does the future hold?

Stevenson Christina E CE Nagahashi Masayuki M Ramachandran Subramaniam S Yamada Akimitsu A Bear Harry D HD Takabe Kazuaki K

Future oncology (London, England) 20120401 4

Breast cancer is a major health concern for many women, but despite the current standard therapies, many women still die of metastatic disease. Angiogenesis has been evaluated as a possible target for therapy and bevacizumab (Avastin(®), Genentech/Roche, CA, USA), a monoclonal antibody against VEGF-A, has been developed to target this. Current clinical trials utilizing bevacizumab have shown an increase in progression-free survival, but this has not translated to an increase in overall survival ...[more]

PMID: 22515444

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Project description:BackgroundBevacizumab and the antimetabolites capecitabine and gemcitabine have been shown to improve outcomes when added to taxanes in patients with metastatic breast cancer. The primary aims of this trial were to determine whether the addition of capecitabine or gemcitabine to neoadjuvant chemotherapy with docetaxel, followed by doxorubicin plus cyclophosphamide, would increase the rates of pathological complete response in the breast in women with operable, human epidermal growth factor receptor 2 (HER2)-negative breast cancer and whether adding bevacizumab to these chemotherapy regimens would increase the rates of pathological complete response.MethodsWe randomly assigned 1206 patients to receive neoadjuvant therapy consisting of docetaxel (100 mg per square meter of body-surface area on day 1), docetaxel (75 mg per square meter on day 1) plus capecitabine (825 mg per square meter twice a day on days 1 to 14), or docetaxel (75 mg per square meter on day 1) plus gemcitabine (1000 mg per square meter on days 1 and 8) for four cycles, with all regimens followed by treatment with doxorubicin-cyclophosphamide for four cycles. Patients were also randomly assigned to receive or not to receive bevacizumab (15 mg per kilogram of body weight) for the first six cycles of chemotherapy.ResultsThe addition of capecitabine or gemcitabine to docetaxel therapy, as compared with docetaxel therapy alone, did not significantly increase the rate of pathological complete response (29.7% and 31.8%, respectively, vs. 32.7%; P=0.69). Both capecitabine and gemcitabine were associated with increased toxic effects--specifically, the hand-foot syndrome, mucositis, and neutropenia. The addition of bevacizumab significantly increased the rate of pathological complete response (28.2% without bevacizumab vs. 34.5% with bevacizumab, P=0.02). The effect of bevacizumab on the rate of pathological complete response was not the same in the hormone-receptor-positive and hormone-receptor-negative subgroups. The addition of bevacizumab increased the rates of hypertension, left ventricular systolic dysfunction, the hand-foot syndrome, and mucositis.ConclusionsThe addition of bevacizumab to neoadjuvant chemotherapy significantly increased the rate of pathological complete response, which was the primary end point of this study. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT00408408.).

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Bevacizumab and breast cancer: what does the future hold?

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Bevacizumab and breast cancer: what does the future hold?

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