Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0268596 (EMA)
 2,520 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A panel of nine monoclonal and polyclonal antibodies were tested regarding specificity for metastatic breast cancer. A hundred metastatic tumors were stained, 50 of breast origin and 50 of other origins. Antibodies used were anti-alpha-lactalbumin, anti-lactoferrin, anti-casein, E29 (Dako-EMA), anti-secretory component, anti-gross cystic disease fluid protein (GCDFP15), BRST1, BRST2, and MC5. Analyses of the results were performed using chi-square and logistic regression. Positivity for MC5, BRST1, BRST2, lactoferrin, EMA, and GCDFP15 was significantly higher in tumors of breast origin than in others (p less than 0.05). Analyses of the whole panel indicated that GCDEP15 and MC5 were the best markers for identification of breast cancer metastases. When both were positive (58% of breast origin cases), the predicted probability of breast origin was 98%, compared to only 5% when both were negative. Comparison of anti-GCDFP15 with BRST2, a monoclonal antibody against the same protein, showed a slightly better sensitivity of the former, and a similar degree of specificity for breast tissue. In conclusion, a panel of antibodies can be used to securely differentiate metastatic breast cancer from other cancers in a large number of metastatic tumors of unknown origin.
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PMID:Immunohistochemical markers in the identification of metastatic breast cancer. 132 17

The growth of normal human breast epithelial cells in vitro, as well as those of other cell types is strongly influenced by the concentration of calcium in the culture medium [Ca++]e. The aim of this study was to ascertain if calcium also affects breast tumor cell growth in vitro. To address this question, the metastatic breast cancer cells MCF-7 were grown at low (0.04 mM, L-Ca) and high (2.5 mM, H-Ca) [Ca++]e. In each culture condition, we estimated intracellular calcium levels (Ca++]i from Indo-1 fluorescence by the ratio method. We showed that [Ca++]i increased with [Ca++]e, the [Ca++]i values ranging from approximately 50 to 250 nM. Changes of [Ca++]i ware accompanied by changes of cell shape and cell kinetic parameters. In H-Ca, cells were flat and 3 times larger than in L-Ca and the percentage of cells in the S+G2+M phases as well as the percentage of Ki-67 positive cells rapidly dropped on days 3-4 of culture in contrast to cells grown in L-Ca. In H-Ca, the cell growth arrest corresponded to maximal [Ca++]i which was stable during the stationary phase; at that time, a switch from H-Ca to L-Ca resulted in a drop of [Ca++]i and a resumption of cell growth.. In H-Ca, modifications in cell differentiation parameters such as diminution of ER expression and increases of lipid content and EMA expression were observed as compared to cells grown m L-Ca. Our results suggest that MCF-7 cells have retained some calcium dependency and that agents that can increase [Ca++]i in breast tumor cells may limit their proliferation and trigger at least a partial differentiation.
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PMID:Intracellular calcium and breast-cancer cell-growth and differentiation. 2157

PI3K/AKT/mTOR pathway is a crucial mediator of tumor progression. As the PI3K/Akt pathway is heavily deregulated in breast cancer, the application of mTOR inhibitors in breast cancer patients seems warranted. This is the first systematic review according to PRISMA guidelines to synthesize all available data of mTOR inhibitors in all subcategories of breast cancer. The search strategy retrieved 16 studies evaluating everolimus (1492 patients), seven studies examining temsirolimus (1245 patients), one study evaluating sirolimus (400 patients) and two studies evaluating MKC-1 (60 patients). The Breast Cancer Trials of Oral Everolimus-2 (BOLERO-2) study has marked a turning point in the evaluation of everolimus in the treatment of estrogen receptor positive breast cancer. Given the positive results, everolimus has entered NCCN 2012 guidelines, and its approval of its combination with exemestane by FDA and EMA is imminent. In addition, the promising antitumor activity and long-term disease control further suggest that mTOR inhibition with everolimus may provide an avenue for achieving long-lasting benefit from trastuzumab-based therapy in HER2-positive patients. Regarding temsirolimus, it seems that the agent may play, in the future, a role in the treatment of metastatic breast cancer; importantly, however, there is an unmet need to find its optimal target subpopulation.
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PMID:mTOR inhibitors in breast cancer: a systematic review. 2296

Eribulin mesylate is a synthetic analog of halichondrin B (a polyether macrolide isolated from a marine sponge). It is a nontaxane microtubule dynamics inhibitor with a novel mechanism of action. It is the first drug that has demonstrated an improvement in overall survival as a single agent compared with the physician's choice of currently available treatments in locally advanced or metastatic breast cancer, previously treated with anthracyclines and taxanes. It has shown a good manageable tolerability profile. This drug has been approved by the US FDA and by the EMA for patients with locally advanced or metastatic breast cancer who have received at least two chemotherapeutic regimens for advanced/metastatic disease. Prior therapy should have included an anthracycline and a taxane in either the adjuvant or metastatic setting unless patients were not suitable for these treatments. The aim of this article is to describe the mechanism of action, pharmacokinetics, pharmacodynamics and the most relevant clinical trials in the development of this drug.
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PMID:Eribulin mesylate in breast cancer. 2416 5

Trastuzumab (TR), a monoclonal antibody approved by EMA in 2000 and one of the first examples of "targeted therapy", is indicated to treat human epidermal growth factor receptor 2 (HER2) positive breast cancer. TR, whose patent will expire in 2015 in Europe, has been judged positively for reimbursement by most public authorities in the EU. Here we critically review the existing evidence on TR in metastatic breast cancer (MBC), in line with the multidisciplinary health technology assessment (HTA) approach, to assess whether the existing evidence supports TR positive reimbursement decisions taken in MBC by EU health authorities. We did a literature search for the main HTA topics (efficacy, quality of life and ethics) on the PubMed international database (2000-2013). Then, we did a specific literature search to select the full economic evaluations (FEEs) conducted in EU countries focused on TR as first-line innovative therapy in MBC. We retrieved scant evidence in the literature to support TR reimbursement in MBC. We found only two clinical trials and their results were unclear because of the large proportion of patients who crossed over. Moreover, the quality of methods was poor in all four European FEEs selected. This example of HTA exercise on a mature monoclonal antibody in a specific indication casts doubts on how often the reimbursement decisions taken by EU health authorities in emotional pathologies like cancer are rational. These decisions should at least be reconsidered periodically on the basis of the latest evidence.
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PMID:Cost-effectiveness of trastuzumab in metastatic breast cancer: mainly a matter of price in the EU? 2552 44

Introduction: In March 2019, atezolizumab became the first immune checkpoint inhibitor to receive a breast cancer-specific approval. Based on a significant improvement in progression-free survival as well as a 10-month improvement in overall survival (on interim analysis) seen in the IMpassion 130 trial, the combination of atezolizumab and nab-paclitaxel was approved for patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC).Areas covered: This article reviews current data and ongoing research on atezolizumab for the treatment of breast cancer. Results of atezolizumab monotherapy trials in the context of other early immune checkpoint blockade trials in breast cancer are discussed as well as data from combination clinical trials with chemotherapy in both early-stage and metastatic breast cancer. We focus on the safety and efficacy analyses from the phase III IMpassion trial that led to FDA and EMA approval of atezolizumab and nab-paclitaxel in patients whose tumor tested positive for PD-L1 by the Ventana SP142 companion diagnostic immunohistochemical assay.Expert opinion: The FDA and EMA approvals of atezolizumab mark an important advance for treatment of metastatic TNBC. However, ongoing investigations need to define better biomarkers of response, determine resistance mechanisms, and identify strategies to increase response rates.
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PMID:Atezolizumab for the treatment of breast cancer. 3206 45

In recent years, the blood-based analysis of circulating tumour cells (CTCs) and nucleic acids (DNA/RNA), otherwise known as liquid biopsy, has become increasingly important in breast cancer. Numerous trials have already underscored the high prognostic significance of CTC detection in both early and metastatic stages. Moreover, the changes in CTC levels and circulating tumour DNA (ctDNA) during the course of the disease correlate with the response to treatment. Research currently focuses on liquid-biopsy based therapeutic interventions in metastatic breast cancer. In this context, alpelisib, a PI3K inhibitor, was the first agent to be approved by FDA and EMA.
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PMID:Liquid Biopsy in Breast Cancer. 3317 37