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)

The development of an oral formulation of vinorelbine (Navelbine softgelatine capsules, Pierre Fabre Pharma, Freiburg i.Br., Germany) represents a significant advance in the treatment of patients with cancer. Oral chemotherapy is more convenient for the patients and brings significant time savings. Vinorelbine is rapidly absorbed after oral ingestion. The bioavailability is in the range of 33 to 43% and is not affected by concomitant food intake or by vomiting occuring 1.5 h or later after dosing. No significant differences in the pharmacokinetics of oral vinorelbine were observed between elderly (> or =70 years) and younger patients. The recommended dose schedule for oral vinorelbine is 60 mg/m(2) weekly for the initial 3 weeks (cycle 1) and 80 mg/m(2) weekly thereafter. However, if severe neutropenia is encountered during the first cycle, treatment is continued with weekly doses of 60 mg/m(2). Bioavailability studies have demonstrated that oral vinorelbine doses of 60 and 80 mg/m(2) are comparable to intravenous doses of 25 and 30 mg/m(2), respectively. Several clinical studies have demonstrated that the new oral formulation of vinorelbine can be safely administered, even to elderly patients, and is comparable in activity to intravenous vinorelbine in advanced non-small cell lung cancer (NSCLC) and metastatic breast cancer (MBC). A randomized phase II comparison of oral vinorelbine at the recommended dose schedule vs. intravenous vinorelbine at 30 mg/(2) in patients with advanced NSCLC found no significant differences in response rate, progression-free and overall survival between the two treatments. In studies of combination chemotherapy using vinorelbine plus cisplatin or carboplatin in advanced NSCLC, or vinorelbine plus taxanes, capecitabine,epirubicin, or the monoclonal HER2/neu antibody trastuzumab in MBC, intravenous vinorelbine could be completely or partially replaced by oral vinorelbine, resulting in maintained efficacy, good tolerability and improved patient convenience. Concurrent chemoradiation with oral vinorelbine and cisplatin was shown to be well tolerated and produced significant down-staging in patients with locally advanced NSCLC. Metronomic chemotherapy is a new treatment approach designed to maximize the antiangiogenic effect. Oral vinorelbine given every other day at low doses is currently evaluated in patients with refractory solid tumors. Oral vinorelbine has also proven useful as a substitute for intravenous vinorelbine in patients experiencing intractable acute tumor pain during or after intravenous infusion of vinorelbine.
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PMID:[Oral vinorelbine: pharmacology and treatment outcome in non-small cell bronchial carcinoma and breast carcinoma]. 1653 41

Monoclonal antibodies are among the most rapidly expanding class of therapeutics for cancer treatment. Monoclonal antibodies targeting non-Hodgkin's lymphoma (NHL), Her-2/neu highly expressing metastatic breast cancer, colorectal cancer, acute myelogenous leukemia, and B-cell chronic lymphocytic leukemia (CLL) have received FDA approval. Promising new targets for antibody therapy include cellular growth factor receptors, mediators of tumor-driven neo-angiogenesis, as well as host negative immunoregulatory checkpoints that impede an effective immune response to neoplasia. Antibody efficacy has been increased by genetic engineering to humanize the antibodies and to increase their effector functions including antibody dependent cellular cytotoxicity. Furthermore, antibodies have been armed with cytokines, chemotherapeutic agents, toxins, and radionuclides to augment their efficacy as tumor cytotoxic agents. As a consequence of these advances, 30 years after their first development, monoclonal antibodies have become an important standard approach for the therapy of neoplasia with 19 therapeutic monoclonal antibodies now approved by the FDA including 8 for the treatment of cancer.
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PMID:Development of antibodies and chimeric molecules for cancer immunotherapy. 1673 Feb 62

The majority of deaths due to breast cancer occur in the context of complications secondary to metastatic disease. Trastuzumab, as a second line treatment, has shown a 15% objective response rate in patients with metastatic breast cancer. We present the case of a patient with two breast tumours, the second of more aggressive characteristics, with negative hormone receptors and c-erb-B2 +++, and with few therapeutic options due to her hepatic insufficiency secondary to metastatic disease; she was administered herceptin as monotherapy, and she had a complete clinical response. Trastuzumab has revolutionised the management of patients with metastatic breast cancer and Her-2- neu overexpression. Its combination with chemotherapy agents achieves a synergic activity.
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PMID:A patient with breast cancer with hepatic metastases and a complete response to herceptin as monotherapy. 1707 77

We report the case of a woman who conceived while being treated on a phase I clinical trial with lapatinib, a dual inhibitor of epidermal growth factor receptor (EGFR) and HER2/neu, for metastatic breast cancer. Despite approximately 11 weeks of exposure to lapatinib in the first and second trimesters, the pregnancy was uncomplicated and resulted in the delivery of a healthy baby. Although concomitant cancer and pregnancy is relatively rare, the increasing use of biologic agents among fertile women, sometimes for as long as a year in the adjuvant setting increases the probability that some women will conceive while taking a growth factor pathway inhibitor. As with systemic chemotherapy given during pregnancy, there exists the potential for teratogenicity or fetal demise from exposure of the developing embryo to inhibitors of EGFR and HER2/neu. Despite the positive outcome of this case, continued caution is warranted with the use of EGFR and HER2/neu inhibitors in pregnancy.
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PMID:Delivery of a healthy baby after first-trimester maternal exposure to lapatinib. 1709 3

Amplification of the her-2/neu gene is associated with poor prognosis in patients with early-stage and metastatic breast cancer. Trastuzumab is a humanized monoclonal antibody directed against the HER2 protein, which is overexpressed in approximately 25% of patients with primary invasive breast cancer. Randomized phase III clinical trials showed that administration of trastuzumab in combination with chemotherapy or following chemotherapy significantly improves disease-free and overall survival rates in patients with early-stage HER2-positive breast cancer. The integration of trastuzumab in the adjuvant setting is changing the natural history of HER2-driven breast cancer from one of the worst subtypes to one that is highly curable with available therapy.
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PMID:The use of HER2 modulation in the adjuvant setting. 1716 42

Of 231 patients with recurrent or metastatic breast cancer treated in Hiei Hospital between January 2001 and March 2005, for whom data on hormone receptor (HR) and HER 2/neu were available, we retrospectively analyzed the association of the response rate with HR and HER 2 in 172 patients treated with taxane in whom the treatment response could be evaluated. Among the patients treated with taxane alone,the response rates were 37.5% (n=67) in the HR (+) patients and 14.6% (n=41) in the HR (-) patients (p=0.0131). In particular, taxane resistance was suggested in the HR (-)/HER 2 (-) patients (response rate: 4.2%, n=24). Concerning combination therapy with trastuzumab and taxane, the response rate were 52.8% in the HR (+)/HER 2 (+) patients and 60.4% in the HR (-)/HER 2 (+) patients. In 27 of these patients, single therapy with taxane was switched to combination therapy with taxane and trastuzumab after they became resistant to taxane, and 8.3% of the HR (+)/HER 2 (+) patients and 53.3% of the HR (-)/HER 2 (+) patients responded to this combination therapy (p=0.0192), suggesting the synergistic effects of the two agents in HR (-)/HER 2 (+) patients. Therefore, HR and HER 2 were associated with the sensitivity to a chemotherapeutic agent, taxane. Stratification with respect to HR and HER 2 is important in the treatment of metastatic breast cancer. In particular, therapeutic strategies for HR (-)/HER 2 (-) patients with a poor prognosis must be established in the future.
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PMID:[Stratification with respect to hormone receptor and HER 2/neu in the treatment of metastatic breast cancer; sensitivity to taxane]. 1722 Jun 70

Two women, aged 57 and 55 years, with metastatic breast cancer were admitted for uncontrolled pain due to bone metastases. Despite the fact that progressive disease was evident, a change in antitumour therapy had not been recommended. The pain control was optimised in both patients. In one patient, palliative chemotherapy was installed, combined with trastuzumab because of HER2/neu overexpression. She was still alive after one and a half year of treatment. The other patient could not adjust mentally to the fact that her palliative therapy was changed to antitumour therapy; she died one month later. It is important to be aware of the various kinds of therapy in metastatic breast cancer because palliative treatment is more than just symptomatic treatment. Systemic antitumour therapy includes hormone therapy, chemotherapy and targeted therapy. Furthermore, in patients with bone metastases, radiotherapy combined with bisphosphonates results in pain relief and can reduce skeletal complications. Because of the ensuing complexity of the treatment of metastatic breast cancer, these patients should be regularly managed by a breast-cancer care team in order to improve the quality of care.
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PMID:[Palliation in patients with metastatic breast cancer often better with antitumour treatment than with only symptomatic treatment]. 1744 91

2B1 is a bispecific murine monoclonal antibody that binds to the extracellular domains of HER2/neu and FcgammaRIII. 2B1 efficiently promotes the lysis of tumor cells overexpressing HER2/neu by natural killer cells and mononuclear phagocytes that express the FcgammaRIII A isoform. Here, we report the results of E3194, a phase 1B/2 trial conducted by the Eastern Cooperative Oncology Group that employed 2B1 therapy in 20 women with metastatic breast cancer. The median age was 51 years. All but 1 patient had received prior chemotherapy. After the first dose, 3 of the initial 8 patients experienced dose-limiting toxicities that required dose-reduction. The nature of these dose-limiting toxicities resulted in a reduced dose from 2.5 mg/m/d to 1 mg/m/d in the remaining 12 patients. Objective antitumor responses were not seen. However, 2B1 therapy induced adaptive immune responses to both intracellular and extracellular domains of HER2/neu. Even though 2B1 antibody therapy did not show activity in metastatic breast cancer at the current administered doses, the ability of this antibody to induce detectable immune responses against an important tumor antigen has implications for understanding the mechanisms by which antibodies that mediate antibody-directed cellular cytotoxicity may exert their clinical antitumor effects.
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PMID:Induction of adaptive Anti-HER2/neu immune responses in a Phase 1B/2 trial of 2B1 bispecific murine monoclonal antibody in metastatic breast cancer (E3194): a trial coordinated by the Eastern Cooperative Oncology Group. 1745 20

The standardization and use of heat-induced epitope retrieval (HIER) is particularly important with immunohistochemical markers that direct the course of cancer treatment, such as Herceptin therapy. Increasingly, many laboratories are performing immunohistochemical analysis using various antibodies and methodologies for HER2/neu. We attempted to determine the effects of antibody clone and pretreatment methods on the interpretation of HER-2/neu staining in cytologic samples. Cell block sections from 54 cases of metastatic breast cancer (24 FNAs, 30 effusions) were analyzed for HER2 expression using antibodies to CB-11, TAB250, and A0485. Antibodies were analyzed with and without HIER. One pathologist using the FDA-approved scoring system for the HercepTest reviewed all slides in a blinded fashion. Five of fifty-four cases (9%) using CB-11 showed a significant increase in HER2 immunoreactivity using HIER (i.e. from 0/1+ to 2-3+). However, in twenty-nine of fifty-four cases (54%), the cytoplasmic background was significantly higher after HIER. With the A0485 antibody, two of fifty four cases (4%) showed a significant increase in immunoreactivity using HIER, while seventeen of fifty-four cases (31%) exhibited only more pronounced cytoplasmic staining. HIER pretreatment did not increase HER2 staining in any TAB250 stained sample, rather four of fifty-four cases (7%) showed a significant decrease in staining with HIER. We conclude that HIER may enhance membrane staining with the CB-11 and A0485 antibodies, but also increases cytoplasmic background. Loss of antigenicity is seen when HIER is used with TAB250.
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PMID:The effects of antibody clone and pretreatment method on the results of HER2 immunostaining in cytologic samples of metastatic breast cancer: A query and a review of the literature. 1749 56

Taxanes (TX) were administered to 246 of 292 patients with recurrent/metastatic breast cancer (MBC) who were treated in Hiei Hospital between January 2001 and May 2006. Recently, TX has been increasingly prescribed for preoperative treatment and postoperative adjuvant therapy. To improve the prognosis of MBC, regimens effective for TX-resistant cancer patients should be developed. In this study, with respect to hormone receptor (HR) and Her 2/neu (HER 2), we retrospectively investigated whether our series responded to the regimens used after TX resistance was acquired. As post TX-resistance therapy (trastuzumab was combined in HER2-positive patients), 387 treatment regimens were administered to 166 patients. The following regimens achieved a response rate (patients achieving PR or CR/patients who could be evaluated) of 10% or more: combination therapy with TX and capecitabine (11/61, 18%), CPT-11 (10/57, 17.5%), vinorelbine (5/46, 10.9%), MFL-P (continuous treatment with MTX, 5-FU, LV, and CDDP) (12/47, 25.5%), and DMpC (5'-DFUR, MPA, CPA p.o.) (5/16, 31.2%). The latter 2 regimens achieved a high response rate,and some HR (-) and HER 2 (-) patients also responded to these regimens. In HR (+) or HER 2 (+) patients who responded to TX, survival was longer than that of non-responders. However, there was no difference in the treatment responsiveness of post-TX regimens between TX-responders and non-responders, suggesting the survival-prolonging effect of TX.
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PMID:[Evaluation of therapeutic regimens for taxane-resistant recurrent/metastatic breast cancer]. 1763 40


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