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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This years ASCO-meeting reinforced the trend of the recent years to get off from empirical treatment concepts to tailored and individualized diagnostics and therapy. However, the basis for an individual therapy is a specific molecular diagnostic which can be reflected in the analysis of hormonal receptor, HER-1, HER-2 and topoisomerase IIalpha in breast cancer. All these markers are not only able to prognosticate the course of disease but they also can predict the success of specific treatment approaches. Trastuzumab is standard therapy in HER-2 positive breast cancer both in the adjuvant and palliative setting. But new therapeutic agents, as e. g. lapatinib, are promising in the treatment of HER-2 positive breast cancer even if trastuzumab is failing. Otherwise it might possibly be an alternative option but adequate clinical results have to be awaited. The targeted inactivation of EGFR-related signal transduction pathways by e. g. gefitinib did not show a substantial improvement neither as a single agent nor in combination with endocrine treatment. However, the appropriate subgroup which might benefit from this therapy has to be defined even if molecular data suggest that patients with ER positive and PR negative breast cancer might be such a group. The increasing knowledge in terms of the biology of bone metastasis led to the development of new treatment options as e. g. denosumab, a humanized monoclonal antibody for RANK ligand. Two adjuvant cytotoxic treatment trials revealed that taxanes improve the prognosis of node positive breast cancer and should be administered sequentially. The advantage of switching to an aromatase inhibitor after two to three years of tamoxifen in endocrine treatment of postmenopausal patients is proved by two clinical trials (IES, ARNO) which could demonstrate a survival benefit. In conclusion it seems to be evident that new targeted therapy options are effective and will set new standards for the treatment of breast cancer patients in the near future. The presentation for the ovarian cancer focused on the addition of a third cytotoxic agent to carboplatin and paclitaxel as the standard therapy for the primary treatment of ovarian cancer. New data of Bevacizumab in the treatment of primary and recurrent ovarian cancer were presented. However, this is not yet a standard treatment for all patients and needs further investigations within large, multicentre, randomised trials. The lymphonodectomy as part of the primary therapy of the endometrial cancer seems to be a benefit at least in patients with advanced disease or high risk stage I tumours. The adjuvant therapy of uterine sarcomas is still not yet very well investigated and clear. A trial which recruited 12 years demonstrated a benefit in overall survival which has to be interpreted with caution. In this year again there have been registered an increasing number of interesting contributions from Germany, which also received international attention.
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PMID:[Molecular diagnostic and targeted therapy--"Barking dogs are going to bite": presentations from the 42nd Annual Meeting of the American Society of Clinical Oncology, Atlanta 2006]. 1700 57

Breast cancer is the most frequent tumor of women. The development of effective adjuvant therapy based on postoperative administration of short-term chemotherapy (4-6 months) or long-term hormone therapy (5 years) or both, significantly improved survival of patients. However, therapy of adjuvant/metastatic disease is still palliative with a very low probability to induce complete remission and definitive cure of disease. The relevant efforts of basic research to identify the key and selective molecular alterations, which sustain breast cancer growth and progression allowed the possibility to develop specific molecular target treatments. Trastuzumab, a humanized monoclonal antibody to HER-2, is the first molecular targeting agent approved for therapy of metastatic breast cancer, capable to significantly improve clinical outcome in combination with cytotoxic therapy. Recent preliminary data from randomized, prospective, clinical trials suggest that trastuzumab decreases the risk of early recurrence by 50% in patients with HER-2-positive disease. Other novel targeted treatments are in clinical evaluation, including antiangiogenic compounds (Bevacizumab, sunitinib, vatalanib, and others) and bi-functional drugs such as lapatinib (anti Her-2 and EGFR agent) showing promising activity. This review provides an updated overview of the status of development of targeted therapy in breast cancer, as well as the challenges related to the rational use of molecular targeting agents.
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PMID:Targeted therapy of breast cancer. 1734 46

Tumor angiogenesis is essential for the growth and metastasis of solid tumors. In breast cancer, increased levels of vascular endothelial growth factor (VEGF) have been associated with poor prognosis in lymph node-positive and lymph node-negative patients. In addition to its prognostic significance, VEGF is now a validated target in the treatment of breast cancer. Bevacizumab, an anti-VEGF antibody, has demonstrated significant clinical benefit in several solid tumors. In this article the authors discuss the data pertaining to bevacizumab and other antiangiogenic agents for the treatment of patients who have advanced breast cancer.
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PMID:Bevacizumab for advanced breast cancer. 1751 51

Estimates suggest that in Europe 2.3% of people older than 65 years have neovascular age-related macular degeneration, which can lead to loss of central vision. The condition is the leading cause of blindness in the estern world, and the third commonest worldwide. It is characterised by growth of new blood vessels beneath the retina (choroidal neovascularisation), a process stimulated by the secretion of vascular endothelial growth factor (VEGF).3 Two new drugs, pegaptanib sodium (Macugen - Pfizer) and ranibizumab (Lucentis -Novartis), that block the effects of VEGF are now licensed in the UK for patients with neovascular age-related macular degeneration. A third drug that inhibits VEGF activity, bevacizumab (Avastin - Roche), is also used for this condition but is licensed only for metastatic colorectal or breast cancer. Here we consider the role of pegaptanib, ranibizumab and bevacizumab in patients with neovascular age-related macular degeneration.
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PMID:A view on new drugs for macular degeneration. 1771 4

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

Monoclonal antibodies have emerged as a class of novel oncology therapeutics. The selectivity and specificity, the unique pharmacokinetics, and the ability to engage and activate the immune system differentiate these biologics from traditional small molecule anticancer drugs. In this review, we focus on 4 antibodies approved for clinical use in treating solid tumors, trastuzumab (Herceptin) for breast cancer, bevacizumab (Avastin) for colorectal cancer and non-small cell lung cancer, cetuximab (Erbitux) for colorectal cancer and head and neck cancer, and panitumumab (Vectibix) for colorectal cancer. The anticancer effects of these antibodies derive from blockade of growth factor/receptor interaction and/or down-regulation of oncogenic proteins (eg, growth factor receptors) on the tumor cell surface, and for some of these antibodies from the ability to elicit effector mechanisms of the immune system, such as antibody-dependent cellular cytotoxicity and complement-mediated cytotoxicity. The mechanism behind each antibody, the registration trials for their approved indications, and emerging indications are the focus of this article. We also review clinical considerations including commonly observed and antibody-related side effects, and dosing schedules. In addition, perspectives on challenges and opportunities of oncology antibody clinical development, antibody engineering, and the use of pharmacogenomics are presented.
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PMID:Antibody-based therapy for solid tumors. 1853 57

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

Bevacizumab is approved for the treatment of colorectal cancer, breast cancer, non-small cell lung cancer and renal cell cancer. Before embracing this expensive agent for many other indications, it remains critical to be aware of the evidence upon which oncologists base their day-to-day clinical practice. In this review, we address the results of clinical studies upon which bevacizumab's current use is based and discuss some future perspectives.
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PMID:The use of bevacizumab in colorectal, lung, breast, renal and ovarian cancer: where does it fit? 1878 79


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