Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bevacizumab, a recombinant humanised monoclonal antibody against vascular endothelial growth factor, is approved in Europe as first-line therapy for metastatic breast cancer (mBC) and metastatic carcinoma of the colon or rectum (mCRC); the European Medicines Agency gave a positive opinion recommending its use in non-small-cell lung cancer (NSCLC) and is also considering other indications. In the US, it is licensed for use for mCRC and NSCLC, with its use as first-line treatment in mBC under review by the US FDA. In the pivotal E2100 trial in >700 previously untreated patients with locally recurrent or mBC, recipients of bevacizumab plus paclitaxel had a statistically and clinically significant increase in progression-free survival versus paclitaxel recipients (13.3 vs 6.7 months; hazard ratio 0.48; p < 0.001) [primary endpoint]. There was also a >2-fold higher objective response rate in the bevacizumab plus paclitaxel arm than in the paclitaxel arm; the between-group difference in median overall survival did not reach statistical significance (25.7 vs 23.8 months). Bevacizumab had an acceptable tolerability profile in these patients, with the majority of adverse events being generally mild to moderate in severity. There are targeted adverse events, including gastrointestinal perforations, wound healing complications and haemorrhage, which although they occur infrequently (incidence <=2%), are potentially life-threatening and may cause morbidity.
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PMID:Bevacizumab: in first-line treatment of metastatic breast cancer. 1768 75

Neo-angiogenesis appears to be a critical feature of tumor growth, migration, and metastasis. Therefore, inhibition of angiogenesis is an appealing strategy for treatment of cancer. Since angiogenesis is the result of several mechanistic processes, controlled by numerable pro- and anti-angiogenic factors and their receptors, multiple possibilities to prevent or reverse tumor-induced neo-vascularization have been proposed. Of these, currently, the most promising approach has been the use of bevacizumab, a humanized monoclonal antibody directed against the most potent pro-angiogenic factor, vascular endothelial growth factor (VEGF). Bevacizumab has been shown to be active in several malignancies, in particular colo-rectal cancer. Although early studies of bevacizumab in far-advanced metastatic breast cancer were disappointing, the results of a recently reported clinical trial by the Eastern Oncology Group comparing first line paclitaxel with or without bevacizumab has demonstrated statistically significant improvements in response rates and time progression. Ongoing studies are now investigating the benefits of bevacizumab with other chemotherapeutic and biologic agents in early metastatic disease as well as in the adjuvant setting. Other anti-angiogenic agents remain in early clinical trials. Small molecular inhibitors of VEGF receptor tyrosine kinase activity, such as sunitinib, appear promising. Nearly 40 years after it was first proposed, inhibition of angiogenesis appears to be gaining a role in medical oncology.
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PMID:Angiogenesis as targeted breast cancer therapy. 1770 41

Over the last few years it has been anticipated that molecularly targeted agents can provide substantial improvement in the treatment of breast cancer. The most illustrative paradigm has been that of trastuzumab (Herceptin), a humanized monoclonal antibody against the HER2 oncoprotein overexpressed in 25% of breast cancers. Trastuzumab when combined with standard cytotoxic chemotherapy improved the outcome and survival in patients with metastatic breast cancer, whereas, over the last 2 years studies incorporating trastuzumab in sequence to or concurrently with taxane-based chemotherapy in the adjuvant setting demonstrated a considerable benefi t in this subset, with the results of longer follow-up regarding long-term outcome and late toxicities expected over the forthcoming years. Moreover, the prognostic and predictive value of topoisomerase IIa (Topo IIa) overexpression in these subgroups with respect to anthracycline treatment has been extensively discussed and analysed. Other inhibitors of both HER1/HER2 have recently been introduced with promising results and results of ongoing studies are awaited with great interest. A recently anticipated target in advanced breast cancer has been the pathway of angiogenesis; first a humanized monoclonal antibody-bevacizumab (Avastin)- has demonstrated encouraging results when combined with chemotherapy in pretreated HER2-negative advanced breast cancer, while combinations with trastuzumab+/-chemotherapy are currently examined in HER2-overexpressing breast cancer. Furthermore, as novel molecular pathways relevant to breast cancer biology are explored, it is expected that a whole array of targeted agents will be tested in combination or in sequence to standard chemotherapy with the aim to improve outcome of high-risk breast cancer patients.
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PMID:Integration of novel targeted therapies into the systemic treatment of breast cancer--a review. 1791 84

Molecular-targeted agents, trastuzumab, lapatinib or bevacizumab, demonstrated efficacy in patients with breast cancer. Trastuzumab exhibited efficacy and safety for HER2-positive metastatic breast cancer, in single usage or in combination with paclitaxel, docetaxel or vinorelbine. Trastuzumab is also useful in an adjuvant setting in HER2-positive early breast cancer. However, it is not clear whether concurrent or sequential treatment is superior. Lapatinib combined with capecitabine showed efficacy against HER2-positive metastatic breast cancer. It was suggested that the combination with lapatinib and paclitaxel was effective. Bevacizumab combined with paclitaxel revealed efficacy for metastatic breast cancer. These molecular-targeted agents play an important role in treatment of breast cancer.
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PMID:[Combined chemotherapy with molecular-targeted agent for breast cancer]. 1848 8

The E-cadherin transcriptional repressor Snail is a prognostic marker for metastatic breast carcinoma, as well as a critical determinant of tumor growth and recurrence. We define a non-angiogenic, autocrine function for the vascular endothelial growth factor-A (VEGF-A) in regulating Snail expression in breast tumor cells. The transfection of well-differentiated breast tumor cells with VEGF-A increases Snail mRNA and protein levels, resulting in reduced E-cadherin expression. Conversely, reducing endogenous VEGF-A expression in poorly differentiated breast tumor cells by siRNA transfection decreases Snail levels. Our studies demonstrate that VEGF and the VEGF receptor Neuropilin-1 increase Snail expression by suppressing the Glycogen Synthase Kinase-3 (GSK-3), an established inhibitor of Snail transcription and protein stability. The VEGF-A neutralizing antibody Avastin was recently approved by the FDA for the treatment of metastatic breast cancer. We present the provocative finding that beyond its anti-angiogenic activity, Avastin can reduce Snail expression in breast tumor cells. Collectively, this work describes a novel autocrine function for VEGF in breast tumor cells in driving the expression of Snail, a breast tumor progression factor. Based on our demonstration that Avastin reduces Snail expression in breast tumor cells, we propose that the treatment of early stage breast cancer patients with Avastin may impede tumor progression.
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PMID:Vascular endothelial growth factor-A stimulates Snail expression in breast tumor cells: implications for tumor progression. 1855 84

In the past few years many encouraging advancements have been made in understanding the molecular mechanisms underlying carcinogenesis and tumor progression. These improvements have led to the identification of promising new targets for cancer therapy. There has been much success with the HER2 targeting antibody trastuzumab (Herceptin) in the treatment of early stage and metastatic breast cancer. Consequently, several antibodies inhibiting cellular signaling of VEGF and EGFR were tested with respect to their efficacy in breast cancer. In phase II and III clinical trials the humanized anti-VEGF antibody bevacizumab (Avastin) alone or in combination with capecitabine exhibited responses in patients with metastatic breast cancer. Recent developments focus on small molecules interfering with different signal transduction pathways in tumor cells. Numerous inhibitors of EGF and VEGF receptor tyrosine kinases and farnesyl transferases are in early stages of clinical development for breast cancer. Another promising approach is the targeting of endothelins and their two G-protein coupled receptors (ET(A)R und ET(B)R). In this article, we will shortly outline well established targeted treatments and discuss the current development of novel agents to be utilized for molecular targeted breast cancer therapy. Due to the heterogeneity of disease and varying response to conventional systemic therapies, these new perceptions may lead to substantial patient benefit and provide a promising basis for future clinical application.
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PMID:Targeted therapies in breast cancer: established drugs and recent developments. 1869 Aug 83

The systemic adjuvant treatment for breast cancer is showing remarkable progress with targeted therapy, such as Trastuzumab, in addition to cytotoxic chemotherapy. The timing of adjuvant chemotherapy is also shifting from post surgery to pre surgery. In terms of adjuvant endocrine therapy for hormonal receptor positive breast cancer, Aromatase inhibitor now is established as a standard treatment for postmenopausal patients. LH-RH analog is also standard for premenopausal patients with Tamoxifen. Further, longer survival might be expected with the new combination of cytotoxic chemotherapy and Trastuzumab for locally advanced or metastatic breast cancer patients. Because the trend of systemic treatment for breast cancer patients is to focus on maintaining patients' quality of life, targeted therapy with Trastuzumab and/or new upcoming drugs (e. g., Bevacizumab, Lapatinib, Sunitinib), might be the mainstream systemic therapy. In this section, we discuss standard and new systemic therapy for primary, locally advanced, and metastatic breast cancer patients.
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PMID:[New period of systemic treatment for breast cancer]. 1879 97

Combination therapy comprising bevacizumab with paclitaxel recently received accelerated approval from the US Food and Drug Administration (FDA) for use in the first-line treatment of patients with metastatic breast cancer. Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF), providing direct inhibition of angiogenesis. The evolution of bevacizumab use in the first-line treatment of patients with breast cancer has been characterized by a logical progression of phase II and III trials that have demonstrated that angiogenesis plays an important role throughout all stages of breast cancer growth and progression. In the phase III clinical trial E2100, which provided the basis for FDA approval, the use of bevacizumab (10 mg/kg on days 1 and 15) plus paclitaxel (90 mg/m2 days 1, 8, and 15 every 28 days) given until disease progression approximately doubled median progression-free survival (PFS; 11.8 months vs. 5.9 months; hazard ratio = 0.60; P < .001) compared with paclitaxel alone; by contrast, a statistically significant improvement in overall survival was not seen with the addition of bevacizumab, although a post hoc analysis demonstrated a significant increase in 1-year survival for the combination arm. The E2100 study, as well as the majority of clinical trial designs for bevacizumab, has used PFS as the primary efficacy endpoint, and, in this review, the development of PFS as a measure of clinical benefit is outlined. This review also discusses the importance of VEGF signaling in early phases of breast tumor progression, which has provided a rationale for the investigation of bevacizumab in early-stage settings.
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PMID:Evolution of bevacizumab-based therapy in the management of breast cancer. 1895 53

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

The growth of new blood vessels, angiogenesis is important for tumour progression and metastasis. Vascular endothelial growth factor (VEGF) plays multiple roles in cancer development. Due to it the VEGF seems to be an optimal therapeutic target in breast cancer therapy. The plasma level of this growth factor is highest early in disease suggests that anti-VEGF agents may provide their greatest benefit in firts-line chemotherapy with metastatic breast cancer (MBC). A phase III trial, E2100 evaluated weekly paclitaxel with or without bevacizumab (Avastin), the specific humanised anti-VEGF monoclonal antibody in patients with previously untreated locally recurrent or MBC, doubling of progression-free survival for all patient subgroups. Bevacizumab is generally well tolerated. The most common adverse events observed in trials hypertension, proteinuria, and wound-healing complications, most of which are grade 1-2 in severity. The registration of bevacizumab for MBC therapy brings new hope for patients. Novel approach of bevacizumab for MBC would be combination chemotherapy and different targeted therapies. Phase III clinical trials of bevacizumab are ongoing in different stages in different settings.
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PMID:[Anti-VEGF therapy with bevacizumab in breast cancer]. 1922 9


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