Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bevacizumab, a humanized monoclonal antibody against vascular endothelial factor (VEGF), is approved for the treatment of metastatic colon cancer, but it has also shown efficacy in first line therapy of non-squamous-cell non-smallcell lung cancer, breast cancer and clear-cell renal cancer. Antiangiogenic therapy severe toxic effects such as stroke, myocardial infraction, angina, arterial thromboembolism, pulmonary embolism or haemorrhage, gastrointestinal perforation, heart failure should be taken into account during treatment with bevacizumab. We describe and discuss two cases of cancer patients who developed fatal arterial thromboembolic episodes after administration of bevacizumab. Due to the recent launch of antiangiogenic agents and the limited experience with their use in clinical practice, their adverse effects and pharmacological toxicities, sometimes fatal, are not well-established and a detailed registration of them is needed.
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PMID:Implication of bevacizumab in fatal arterial thromboembolic incidents. 1936 80

Increased levels of vascular endothelial growth factor (VEGF) have been associated with a poor prognosis for patients with breast cancer. In addition to its prognostic role, VEGF is also a validated target in the treatment of this disease. 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, HER2-negative breast cancer. In this paper, the clinical trials establishing bevacizumab use for the treatment of breast cancer are reviewed.
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PMID:Bevacizumab in the treatment of metastatic breast cancer. 1947 63

The selection of first-line chemotherapy for metastatic breast cancer (MBC) is complex because of the myriad of treatment options available and the inherent biologic heterogeneity of the disease. The potential treatment options are greatly influenced by estrogen and progesterone receptor and HER2 status of the tumor, and biopsy with reassessment of these markers at the time of disease recurrence is strongly recommended. Metastatic breast cancer is generally an incurable disease, with survival that could range from months to several years. Important but modest improvements in overall survival (OS) have been observed for women with MBC over the past few decades, in part because of improvements in systemic therapy. For women with endocrine-responsive disease, hormonal therapy is the appropriate initial treatment choice at the time of disease recurrence with rare exception. Initiation of systemic chemotherapy is appropriate for women with disease that is either hormone receptor negative, endocrine therapy refractory, or rapidly progressive with visceral involvement. The addition of trastuzumab to chemotherapy for women with HER2-positive breast cancer represents a clear standard of care. For HER2-negative MBC, sequential single-agent chemotherapy is preferred over combination therapy as a result of the more favorable toxicity profile and absence of a clinically significant improvement in survival with combination treatment. Many single-agent chemotherapeutic agents have activity in MBC, with most data supporting an anthracycline- or taxane-based approach. Bevacizumab in combination with chemotherapy prolongs progression-free survival in women with MBC, though its position in the first-line treatment of MBC relative to standard chemotherapy remains unclear at this time because of lack of OS benefit.
Clin Breast Cancer 2009 Jun
PMID:First-line chemotherapy for metastatic breast cancer. 1959 45

The heterogeneity of metastatic breast cancer mandates the need to select therapies taking into account tumor and patient characteristics. Chemotherapy is indicated in the palliative setting especially when the disease is unresponsive to hormonal therapy or is hormone-receptor negative. The main chemotherapeutic agents are anthracyclines, taxanes, and capecitabine. The knowledge of the effects of currently approved agents and of the biology of breast cancer have paved the way for the evaluation of new treatment options, among which are anti-angiogenic agents. Angiogenesis inhibition has resulted in clinically significant improvements in the outcome of a variety of malignancies, including breast cancer. Bevacizumab, a monoclonal antibody anti-vascular endothelial growth factor (VEGF), is the most extensively studied anti-angiogenic compound. According to the results of a phase III trial in patients with untreated metastatic breast cancer, bevacizumab increases both objective response rate and median progression-free survival when combined with standard chemotherapy vs chemotherapy alone. The combination of anti-angiogenic drugs and other biologic agents is also being explored in an attempt to improve efficacy.
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PMID:First line targeted therapies in breast cancer: focus on bevacizumab. 1970 43

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

Choroidal neovascularisation is a potentially visually devastating element of various forms of eye pathology. Recent research has focused on neurovascular age-related macular degeneration (AMD) as a cause. AMD can be classified as being exudative (wet) or atrophic (dry). Wet AMD is characterised by a pathological process in which new blood vessels develop in the choroids, causing leakage of fluid and haemorrhage under the retina and leading to localised serous detachment and loss of central vision. Vascular endothelial growth factor (VEGF) stimulates growth of neovascular membranes. Treatments have until recently yielded disappointing results. Ophthalmologists are using intra-ocular injections of bevacizumab (Avastin), an anti-VEGF, to treat AMD. Avastin appears to be safe and effective in the short term, but its intra-ocular administration is entirely off-label. Avastin is registered for treating metastatic colorectal and breast cancer. The off-label use of medication is an important part of mainstream, legitimate medical practice worldwide. Lawyers representing plaintiffs injured by drugs increasingly encounter off-label use claims. From a legal/ethical point of view the off-label use of medication represents a delicate balance between the statutory regulation of medication and a physician's prerogative to prescribe medication that in his or her medical opinion will be beneficial to the patient. The main reason for the controversy created by the off-label use of Avastin is that there are anti-VEGF drugs on the market that have formal approval for the treatment of AMD (and other eye conditions). Lucentis, for example, is extremely expensive, with treatment cost approximately 50 times that of Avastin. Many patients suffering from AMD and macular oedema cannot afford the registered product. The off-label use of Avastin has passed the innovative or experimental stages, as ophthalmologists have used it regularly and openly for a long time, with good success. Such use therefore cannot be considered careless, imprudent or unprofessional. We submit that an ophthalmologist who omits to inform a patient of the availability of Avastin for this form of treatment may be found to be negligent. Protocols developed by the South African Vitreoretinal Society and endorsed by the Ophthalmological Society of South Africa for administering Avastin and other intra-ocular medication intravitreally should be strictly adhered to.
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PMID:Clinical, legal and ethical implications of the intra-ocular (off-label) use of bevacizumab (avastin)--a South African perspective. 1973 43

Elderly women constitute a large group of breast cancer patients, and after multidimensional geriatric assessment (MGA) only a minor part of them are found in perfect health (=fit), while the remaining display one or more physical or functional limitations or familial/social problems and are therefore categorized as vulnerable or frail (=unfit). Although randomized trials have not produced modest evidence that surgery impacts on ultimate survival of elderly women with hormone-responsive tumors, there is a general consensus that age alone should not prevent surgical local treatment even in unfit women due to the limited morbidity of breast surgery and to the risk of local progression. Activity and safety of AIs appear comparable in elderly women compared to younger counterparts, although concomitant cardiovascular comorbidity and osteoporosis should be closely monitored. Of note, compliance to oral therapy in unfit women and possible interferences with concomitant medications are still poorly documented issues. With the exception of high-risk node positive and estrogen-receptor negative patients, administration of adjuvant chemotherapy for estrogen-receptor positive unfit patients is rarely recommended since the uncertain gain in relapse-free survival is exceeded by the increased risk of toxicity and competitive causes of death. Endocrine-responsive metastatic disease is managed with one or more lines of endocrine treatment as in younger patients. Single agent sequential chemotherapy regimens are to be preferred to combination regimens, which are usually more toxic with a limited survival gain even in younger patients. When and how dose reductions should be applied to unfit patients is highly controversial. Trastuzumab in association with chemotherapy can be administered to elderly patients presenting HER2 overexpressing tumors, although the risk of cardiac adverse events in unfit patients is largely unknown. Bevacizumab-based combinations increase the activity and also toxicity of taxane chemotherapy, and are not a preferred option.
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PMID:Management of primary and advanced breast cancer in older unfit patients (medical treatment). 1976 56

Current evidence indicates that angiogenesis plays an important role in the pathogenesis of several malignancies, including breast cancer. Bevacizumab is a monoclonal antibody that targets the vascular endothelial growth factor (VEGF). Recent clinical data have demonstrated that the addition of bevacizumab to first-line chemotherapy improves the progression-free survival (PFS) of patients with advanced breast cancer. This review presents an update on the clinical studies evaluating the role of bevacizumab in combination with chemotherapy, as well as other agents, both in advanced and early disease. Moreover, although no definitive biomarkers have been identified so far, we provide current data regarding potentially useful predictive factors for treatment with bevacizumab. In addition, we review the suggested mechanisms that lead to resistance to VEGF targeted therapies and we present recent data with respect to the toxicity of bevacizumab.
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PMID:Bevacizumab in the treatment of breast cancer. 1993 67

Angiogenesis is essential for normal tissue and even more so for solid malignancies. At present, inhibition of tumor angiogenesis is a major focus of anticancer drug development. Bevacizumab, a humanized antibody against VEGF, was the first antiangiogenic agent to be approved for advanced non-small cell lung cancer, breast cancer and colorectal cancer. The most commonly observed adverse events are hypertension, proteinuria, bleeding and thrombosis. Sunitinib, a small molecule blocking intracellular VEGF, KIT, Flt3 and PDGF receptors, which regulate angiogenesis and cell growth, is approved for the treatment of advanced renal cell cancer (RCC) and malignant gastrointestinal stromal tumor. The most frequent adverse events include hand-foot syndrome, stomatitis, diarrhea, fatigue, hypothyroidism and hypertension. Sorafenib, an oral multikinase inhibitor, is approved for the second-line treatment of advanced RCC and upfront treatment of advanced hepatocellular carcinoma. Most common adverse events with sorafenib are dermatologic (hand-foot skin reaction, rash, desquamation), fatigue, diarrhea, nausea, hypothyroidism and hypertension. More recently, cardiovascular toxicity has increasingly been recognized as a potential adverse event associated with sunitinib and sorafenib treatment. Elderly patients are at increased risk of thromboembolic events when receiving bevacizumab, and potentially for cardiac dysfunction when receiving sunitinib or sorafenib. The safety of antiangiogenic drugs is of special concern when taking these agents for longer-term adjuvant or maintenance treatment. Furthermore, newer investigational antiangiogenic drugs are briefly reviewed.
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PMID:Antiangiogenic drugs in oncology: a focus on drug safety and the elderly - a mini-review. 1994 Apr 66

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


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