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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Breast cancer is the most common malignancy in women worldwide, and represents the leading cause of death in the female population. Incidence of breast cancer increases with age, and older patients are more likely to have disseminated disease at diagnosis. For those patients who relapse after endocrine treatment or in which the tumor does not express hormone receptors, chemotherapy should be considered. Single agent sequential regimens should be preferred to combination regimens, which are usually more toxic and provide a limited survival gain. New drugs which have proven efficacy against metastatic breast cancer are Taxanes (Paclitaxel and Docetaxel), Vinorelbine, Capecitabine, Gemcitabine, various and newer formulations of Anthracyclines (Epirubicin, oral Idarubicin, liposomal Doxorubicin). The anti-HER2 monoclonal antibody Trastuzumab in association with chemotherapy can be administered to elderly patients who present with HER2 overexpressing tumors, though cardiac monitoring is necessary due to cardiac adverse events. Bevacizumab, an anti-VEGF monoclonal antibody, was recently patented and approved in combination with Paclitaxel for the treatment of metastatic breast cancer. Globally, there is need to develop therapeutics able to circumvent resistance against hormonal and other therapies for advanced breast cancer, which are expected to be safe and effective in this age class.
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PMID:Chemotherapy and targeted agents for elderly women with advanced breast cancer. 1899 87

Bevacizumab (Avastin, Genentech, Inc, San Francisco, CA), a humanized monoclonal antibody against vascular endothelial growth factor, was recently approved for the treatment of metastatic breast cancer.A PubMed and OVID search was performed using keywords: bevacizumab, Avastin, wound healing, VEGF, angiogenesis, and colorectal cancer. Our objective was to review the current literature in regard to bevacizumab and its adverse effects on surgical wound healing.Bevacizumab has been associated with multiple complications in regard to wound healing, such as dehiscence, ecchymosis, surgical site bleeding, and wound infection. Current literature suggests patients should wait at least 6 to 8 weeks (>40 days) after cessation to have surgery (half-life = 20 days). In addition, postoperative reinitiation of bevacizumab must wait > or =28 days to prevent an increased risk of wound healing complications, and the surgical incision should be fully healed.The adverse effects of bevacizumab in regard to wound healing must be considered in all surgical patients.
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PMID:A review on bevacizumab and surgical wound healing: an important warning to all surgeons. 1946 Dec 91

Angiogenesis has a clear and definite role in the breast cancer progression process, making antivascular endothelial growth factor (VEGF) therapies an attractive option for the treatment of metastatic breast cancer (MBC). Bevacizumab is a potent humanized monoclonal antibody to VEGF, which has shown regression of breast cancer in preclinical and clinical setting, either alone or in combination with cytotoxic treatment. Additionally, bevacizumab potentially increases the effectiveness of other anticancer therapies through the normalization of tumor vasculature, reduction of intratumoral pressure and improved tumor oxygenation. Phase 1/2 trials showed significant antitumor effects of bevacizumab in MBC, in particular in tumors not expressing HER2 receptor. A first phase 3 trial in pre-treated MBC patients showed better response rates but no survival benefit from the addition of bevacizumab to capecitabine. However, in two phase 2 trial in first-line setting in patients with MBC, bevacizumab improved progression-free survival in combination with weekly paclitaxel in comparison to paclitaxel alone or in combination with 3-weekly docetaxel in comparison with docetaxel alone, respectively. Bevacizumab in combination with taxanes seems to be a highly effective first-line treatment for MBC patients. Future research will investigate bevacizumab in the neoadjuvant or adjuvant setting, where even more potential may exist for these patients.
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PMID:Bevacizumab in the treatment of HER2-negative breast cancer. 1970 60

One of the most significant developments in medical oncology practice has been the approval of various antiangiogenic drugs for the treatment of a number of different malignancies. These drugs include bevacizumab (Avastin), the anti-VEGF monoclonal antibody. Thus far, bevacizumab appears to induce clinical benefit in patients who have advanced metastatic disease only or primarily when it is combined with conventional chemotherapy. The reasons for the chemo-enhancing effects of bevacizumab are unknown, and this is a subject that we have been actively studying along with additional ways that antiangiogenic drugs may be combined with chemotherapy. In this respect, we have focused much of our effort on metronomic low dose chemotherapy. We have been studying the hypothesis that some chemotherapy drugs at maximum tolerated doses or other cytotoxic- like drugs such as acute "vascular disrupting agents" (VDAs) can cause an acute mobilization of proangiogenic cells from the bone marrow which home to and colonize the treated tumors, thus accelerating their recovery. These cells include endothelial progenitor cells. This systemic process can be largely blocked by a targeted antiangiogenic drug, e.g. anti-VEGFR-2 antibodies. In addition, metronomic chemotherapy, i.e., close regular administration of chemotherapy drugs at low non-toxic doses with no breaks, over prolonged periods of time not only prevents the acute CEP bone marrow response, but can even target the cells. This potential antiangiogenic effect of metronomic chemotherapy can also be boosted by combination with a targeted antiangiogenic agent. Treatment combinations of metronomic chemotherapy and an antiangiogenic drug have moved into phase II clinical trial testing with particularly encouraging results thus far reported in metastatic breast and recurrent ovarian cancer. Oral chemotherapy drugs such as cyclophosphamide (CTX), methotrexate are the main chemotherapeutics used for such trials. Oral 5-FU prodrugs such as UFT would also appear to be highly suitable based on long term adjuvant therapy studies in patients. Recent preclinical results using metronomic cyclophosphamide and metronomic UFT in models of advanced metastatic breast cancer suggest that this type of combination might be particularly promising for metronomic chemotherapy in this indication, particularly when combined with a targeted antiangiogenic drug.
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PMID:Improving conventional or low dose metronomic chemotherapy with targeted antiangiogenic drugs. 1974 37

One of the major recent clinical advances in cancer treatment is the use of antiangiogenic drugs such as bevacizumab, sorafenib, and sunitinib. Bevacizumab, the monoclonal anti-VEGF antibody, has been approved for the first line treatment of metastatic breast cancer (MBC) when combined with taxane. However, the clinical benefits are modest; despite a doubling of response rates and significant prolongation of progression free survival times, no increase in overall survival is attained. This review summarizes some of the possibilities to account for this discrepant result. These include rapid development of acquired drug resistance due to the redundancy of proangiogenic growth factors, acceleration of tumor growth after antiangiogenic drug treatments are stopped, and increases in tumor cell malignant aggressiveness driven by mechanisms such as increased tumor hypoxia. Some possible strategies to improve the benefits of antiangiogenic drug therapy are discussed such as prolonging the treatment beyond tumor progression, combination with other therapeutic modalities, e.g. long term ('maintenance') low-dose metronomic chemotherapy or additional targeted/biologic drugs, e.g. trastuzumab.
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PMID:Issues regarding improving the impact of antiangiogenic drugs for the treatment of breast cancer. 1991 41

Bevacizumab is a humanized monoclonal antibody to VEGF, and the incorporation of bevacizumab to chemotherapy is one of the rapidly evolving areas in the treatment of breast cancer. Bevacizumab in combination with chemotherapy versus chemotherapy alone improves progression-free survival and increases the response rate in first-line therapy for locally recurrent or metastatic breast cancer. This approach has been and is still being evaluated for early breast cancer in neoadjuvant and adjuvant settings. Bevacizumab is well tolerated and has an established tolerability profile. Both tumor- and host-related biomarkers of bevacizumab activity, response and benefit are emerging from Phase I, II and III clinical trials. The biomarkers of benefit will ultimately help identify the subgroups of patients who specifically benefit from anti-VEGF therapy with bevacizumab.
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PMID:Bevacizumab and breast cancer: current therapeutic progress and future perspectives. 1995 82

Tumor angiogenesis is an important step in breast cancer development, progression, invasion and metastasis. Pro-angiogenic factors such as VEGF regulate angiogenesis and are targets for drug development. Bevacizumab, an anti-VEGF antibody, has demonstrated significant clinical benefit in several solid tumors, including breast cancer. Its use in combination with either paclitaxel or docetaxel has prolonged progression-free survival and increased response rates in the first-line treatment of patients with metastatic breast cancer. This review article discusses the clinical trials establishing the use of bevacizumab for the treatment of advanced breast cancer.
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PMID:Bevacizumab for advanced breast cancer. 2000 67

Numerous studies have demonstrated that angiogenesis and in particular VEGF over-expression play an essential role in the progression and metastatic potential of breast cancer. Bevacizumab is a humanized recombinant monoclonal antibody that specifically blocks the binding of VEGF to high-affinity receptors and it has been recently used for the treatment of metastatic breast cancer. We conducted a meta-analysis to synthesize available evidence for use of bevacizumab in metastatic breast cancer patients. Systematic review and meta-analysis of available trials. Primary outcomes were overall survival, progression free survival (PFS) and objective response rate (ORR). Five trials were identified with 3,163 eligible patients. Combination of bevacizumab and chemotherapy resulted in a statistically significant improvement in PFS (HR = 0.70, 95% CI 0.60-0.82, P = 9.3 x 10(-6)) and ORR (RR = 1.26, 95% CI 1.17-1.37, P = 9.96 x 10(-9)) compared with chemotherapy alone. Differences in objective response rates were substantial independently by the type of chemotherapy used, while PFS advantages were observed only for taxanes. The pooled HR for overall survival did not show significant advantage for the use of bevacizumab compared to placebo arm (HR = 0.90, 95% CI 0.80-1.03, P = 0.119). This meta-analysis shows that the addition of bevacizumab to chemotherapy offers meaningful improvement in PFS and ORR in patients with metastatic breast cancer. Bevacizumab treatment might be suggested for treatment of 1st line metastatic breast cancer, but more data are needed until statistical overall survival differences will be documented and firm guideline recommendation could be given.
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PMID:Bevacizumab in metastatic breast cancer: a meta-analysis of randomized controlled trials. 2049 65

Bone likely provides a hospitable environment for cancer cells as suggested by their preferential localization to the skeleton. Previous work has shown that osteoblast-derived cytokines increased in the presence of metastatic breast cancer cells. Thus, we hypothesized that osteoblast-derived cytokines, in particular IL-6, MCP-1, and VEGF, would be localized to the bone metaphyses, an area to which breast cancer cells preferentially traffic. Human metastatic MDA-MB-231 breast cancer cells were inoculated into the left ventricle of the heart of athymic mice. Three to four weeks later, tumor localization within isolated femurs was examined using muCT and MRI. In addition, IL-6, MCP-1, and VEGF localization were assayed via immunohistochemistry. We found that MDA-MB-231 cells colonized trabecular bone, the area in which murine MCP-1 and VEGF were visualized in the bone matrix. In contrast, IL-6 was expressed by murine cells throughout the bone marrow. MDA-MB-231 cells produced VEGF, whose expression was not only associated with the breast cancer cells, but also increased with tumor growth. This is the first study to localize MCP-1, VEGF, and IL-6 in bone compartments via immunohistochemistry. These data suggest that metastatic cancer cells may co-opt bone cells into creating a niche facilitating cancer cell colonization.
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PMID:Localization of osteoblast inflammatory cytokines MCP-1 and VEGF to the matrix of the trabecula of the femur, a target area for metastatic breast cancer cell colonization. 2044 21

Breast carcinoma remains the most common malignancy of women around the world, and despite the advances in the early diagnosis and adjuvant treatment of this disease, many women still relapse with metastatic breast cancer. There is therefore an urgent need for the development and testing of novel agents targeting pathways thought to be involved in the pathogenesis of breast cancer. Aberrant activation of the Ras/Raf/MAPK/ERK kinase/extracellular signal-regulated kinase cascade and the VEGF pathway are commonly observed in breast cancer cells leading to malignant cell proliferation, cell growth, prevention of apoptosis, tumor invasion and neo-angiogenesis. Sorafenib is an oral multikinase inhibitor that inhibits tumor growth and proliferation by interfering with several receptor tyrosine kinases involved in the pathogenesis and perpetuation of malignant breast cancer cells. This article reviews previous experiences and current and future development strategies of sorafenib in breast cancer.
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PMID:Clinical overview of sorafenib in breast cancer. 2046 81


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