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)

Brain metastases occur in as many as one third of patients with disseminated breast cancer. In this article, we discuss various presentations of brain metastases from breast cancer and review evidence that supports different treatment options. Because no prospective, randomized, controlled studies, to our knowledge, have focused solely on patients with brain metastases from breast cancer, we will first review retrospective studies of patients with brain metastases from breast cancer. Randomized studies of patients with brain metastases caused by multiple primary cancers will also be examined, and the conclusions from these studies will be extrapolated to patients with breast cancer. Because brain metastases from breast cancer occur in a variety of different clinical settings, ranging from a single metastasis without extensive extracranial disease to multiple brain metastases with widespread extracranial disease, treatment approaches must be tailored to the specific circumstances of each patient. For different clinical scenarios, neurosurgical resection, radiosurgery, and/or whole-brain radiation therapy may be appropriate treatment options. For patients with brain metastases from breast cancer that overexpresses HER2/neu, trastuzumab could alter the natural history of the non-central nervous system (CNS) disease. Therefore, HER2 status could also influence the treatment of brain metastases from breast cancer. Given the prevalence of brain metastases in patients with metastatic breast cancer in contemporary series, the rationale for clinical trials of CNS screening and prophylactic cranial irradiation will be discussed.
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PMID:Brain metastases in patients with breast cancer: new horizons. 1600 89

We evaluated the safety and efficacy of capecitabine in 12 patients with anthracycline and/or taxane-resistant metastatic breast cancer on an outpatient basis. Their mean age was 57 years, and they previously received chemotherapy consisting of anthracycline in 7 cases, taxane in 12 and doxifluridine in 8. Their mean disease-free interval was 28.5 months, HER 2/neu and ER and/or PgR-positive was shown in 2 and 8 cases, respectively. The recurrent sites were lymph node in 9 cases, lung in 6, skin in 5, pleural effusion in 4, liver, bone and pleura in 3, brain and CBS in 2, and thyroid, ascites and pericardial effusion in one, respectively. The administration dose was 2,400 mg/day in 11 cases and 3,000 mg/day in one. Capecitabine was administered orally for 21 consecutive days followed by a one-week rest. The mean follow-up period was 6.5 months. The overall response rate was 18.2% in 11 cases, including 2 partial responses, 4 stable diseases and 5 progressive diseases. Clinical benefit was 36.4% including two long stable diseases. The mean time to treatment failure was 6.5 months. Adverse events included Hand-Foot Syndrome in 5 cases, nausea in 3, diarrhea, appetite loss and high fever in one, respectively. In two of them administration was discontinued due to adverse events. Capecitabine had satisfactory effects with tolerable adverse events for anthracycline- and/or taxane-resistant metastatic breast cancer.
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PMID:[Experience with capecitabine in patients with anthracycline and/or taxane-resistant recurrent breast cancer]. 1612 15

Over the last two decades, various research protocols were applied for scintigraphic imaging, prognosis and treatment of breast cancer, using monoclonal antibodies. Monoclonal antibodies approved by the United States Food and Drug Administration (FDA) include the anti-carcinoembryonic antigen (CEA), and B72.3, prepared against the tumour-associated glycoprotein, TAG-72. The recombinant humanized "cold" anti-HER2 monoclonal antibody (trastuzumab), which targets oncogene receptor HER2 has hitherto been the only monoclonal antibody widely used for the treatment of breast cancer in the USA, with or without chemotherapy. Trastuzumab is constructed against the HER2 oncogene receptor (also known as neu or c-erb-B2), which is overexpressed in 25%-30% of breast cancer cell lines and is associated with poor prognosis. Immuno-lymphoscintigraphy is also applied to guide and monitor the effect of treatment regimes. Radiolabelled, "hot" monoclonal antibodies are currently being applied for the treatment of primary or metastatic breast cancer, in experimental, pre-clinical, or clinical trials, in combination with traditional external beam radiotherapy and/or chemotherapy. Radioimmunotherapy comprises systemically administered monoclonal antibodies, linked to high-energy, beta-emitting radionuclides. Radioactive antibodies, in the form of yttrium-90 (90Y)-BrE-3, 90Y- m170 and 131I- or 90Y- labelled L6 antibody, are applied with adjuvant autologous peripheral blood stem cells transfusion, to prevent myelotoxicity. Partial or rarely complete responses to "hot" antibody treatment, of breast cancer have been reported. Innovative strategies using this combined-modality treatment hold promise for better disease-free and survival rates.
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PMID:Monoclonal antibodies: old and new trends in breast cancer imaging and therapeutic approach. 1614 51

Her-2/neu overexpression in human breast cancer leads to an aggressive biological behavior and poor prognosis. Although the anti-Her-2/neu antibody trastuzumab (Herceptin(R)) has become a valuable therapeutic option for patients with Her-2/neu-overexpressing breast cancer, many patients do not benefit from this therapy. To evaluate the effect of receptor activation on tumor response, we have investigated the phosphorylation status of Her-2/neu and EGFR in 46 Her-2/neu-overexpressing tumor samples from trastuzumab-treated metastatic breast cancer patients by immunohistochemistry. Activated (p)tyr-1248 Her-2/neu was detected in 9 of 46 breast cancers (20%), and activated (p)tyr-845 and (p)tyr-1173 EGFR were both present in 6 tumors (13%) while EGFR was present in 16 cases (35%). ptyr-1248 Her-2/neu showed a trend to correlate with increased response to trastuzumab (p = 0.063), while ptyr-845, ptyr-1173 EGFR and EGFR did not. The presence of ptyr-1248 Her-2/neu and ptyr-845 or ptyr-1173 EGFR, however, was a strong predictor of both response to trastuzumab-based treatment (OR = 8.0, p = 0.021 and OR = 8.0, p = 0.021) and clinical benefit (OR = 5.47, p = 0.041 and OR = 6.22, p = 0.028 multivariate logistic regression analysis). Furthermore, ptyr-845 EGFR and ptyr-1248 Her-2/neu were both independent predictors of progression-free survival (RR = 0.21, p = 0.01 and RR = 0.45, p = 0.026, multivariate analysis). Patients with ptyr-845 EGFR positive tumors also tended toward increased overall survival (RR = 0.17, p = 0.082). Taken together, we have demonstrated that the determination of activated EGFR improves the utility of ptyr-1248 Her-2/neu staining in predicting the clinical outcome of patients undergoing trastuzumab treatment. We hypothesize that the activation state of both Her-2/neu and EGFR are key determinants for trastuzumab efficacy.
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PMID:Her-2/neu and EGFR tyrosine kinase activation predict the efficacy of trastuzumab-based therapy in patients with metastatic breast cancer. 1616 Oct 43

Tumor metastasis is the major cause of morbidity and mortality in patients with breast cancer. It is critical to identify metastasis enabling genes and understand how they are responsible for inducing specific aspects of the metastatic phenotype to allow for improved clinical detection and management. Protein kinase C epsilon (PKC epsilon), a member of a family of serine/threonine protein kinases, is a transforming oncogene that has been reported to be involved in cell invasion and motility. In this study, we investigated the role of PKC epsilon in breast cancer development and progression. High-density tissue microarray analysis showed that PKC epsilon protein was detected in 73.6% (106 of 144) of primary tumors from invasive ductal breast cancer patients. Increasing PKC epsilon staining intensity was associated with high histologic grade (P = 0.0206), positive Her2/neu receptor status (P = 0.0419), and negative estrogen (P = 0.0026) and progesterone receptor status (P = 0.0008). Kaplan-Meier analyses showed that PKC epsilon was significantly associated with poorer disease-free and overall survival (log-rank, P = 0.0478 and P = 0.0414, respectively). RNA interference of PKC epsilon in MDA-MB231 cells, an aggressive breast cancer cell line with elevated PKC epsilon levels, resulted in a cell phenotype that was significantly less proliferative, invasive, and motile than the parental or the control RNA interference transfectants. Moreover, in vivo tumor growth of small interfering RNA-PKC epsilon MDA-MB231 clones was retarded by a striking 87% (P < 0.05) and incidence of lung metastases was inhibited by 83% (P < 0.02). PKC epsilon-deficient clones were found to have lower RhoC GTPase protein levels and activation. Taken together, these results revealed that PKC epsilon plays a critical and causative role in promoting an aggressive metastatic breast cancer phenotype and as a target for anticancer therapy.
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PMID:Protein kinase C epsilon is a predictive biomarker of aggressive breast cancer and a validated target for RNA interference anticancer therapy. 1616 14

The management of breast cancer during pregnancy is a crucial clinical issue. It is important to evaluate the impact of chemotherapy on a woman and her fetus. Studies from our institution have demonstrated the safety and efficacy of treating women with adjuvant 5-fluorouracil/doxorubicin/cyclophosphamide during the second or third trimester of pregnancy. However, the literature regarding the treatment of metastatic breast cancer in a pregnant patient is scarce. In this article, we describe the successful treatment of a woman at 27 weeks of pregnancy with recurrent HER2/neu-overexpressing breast cancer who was symptomatic from multiple liver metastases. Per our review of the literature and to our knowledge, she is the first patient to be treated with weekly vinorelbine plus trastuzumab. Our patient had near complete resolution of her disease and delivered a healthy male infant at 34 weeks of gestation.
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PMID:Treatment of metastatic breast cancer with trastuzumab and vinorelbine during pregnancy. 1627 87

The characterization of tumor antigens recognized by immune effector cells has opened the perspective of developing therapeutic vaccines in the field of breast cancer. The potential advantages of the vaccines are: (i) the induction of a robust immune response against tumors that are spontaneously weekly immunogenic; (ii) the tumor specificity for some antigens; (iii) the good tolerance and safety profile and (iv) the long-term immune memory, critical to prevent efficiently tumor recurrence. Most trials evaluating breast cancer vaccines have been carried out in patients with extended metastatic breast cancer, characterized by aggressive tumors, resistant to standard cytotoxic treatments, so that clinical efficacy was difficult to achieve. However, some significant immune responses against tumor antigens induced upon vaccinations were recorded. The aim of this review is to analyze the activity of vaccination strategies in current clinical trials. Data of clinical activity have been observed by using vaccines targeting HER2/neu protein, human telomerase reverse transcriptase, carcinoembryonic antigen and carbohydrate antigen given after stem cell rescue. The review discusses possible future directions for vaccine development and applications in the adjuvant setting.
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PMID:Breast cancer vaccines: a clinical reality or fairy tale? 1629 74

The antibody trastuzumab inhibits signal transduction in Her-2/neu overexpressing human breast cancer. However, the activation of co-expressed EGFR has also been show to additionally modulate the anti-tumoural effects of this drug. Similar to Her-2/neu, the extra cellular binding region of EGFR is believed to be proteolytically released from the cell surface upon receptor activation and can be detected in patients' serum (sEGFR). Considering the biological significance of an interaction between EGFR and Her-2/neu signalling in other human malignancies, we have investigated if trastuzumab treatment would affect sEGFR in 33 patients with Her-2/neu overexpressing metastatic breast cancer. We detected EGFR expression in 33% of Her-2/neu overexpressing breast tumours. In contrast to serum Her-2/neu (ECD) levels, which were correlated with the degree of Her-2/neu expression (P=0.048, Mann-Whitney test), we did not detect significant differences between sEGFR serum levels in EGFR expressing or non-expressing tumours. Furthermore, sEGFR serum levels were not correlated with clinical parameters such as response or clinical benefit rates, and no association was found between increased sEGFR levels and progression-free survival or overall survival. While we have previously observed a selective and significant decrease of ECD levels in patients who derived a clinical benefit from trastuzumab treatment during the first weeks of treatment, we were unable to find similar alterations in sEGFR concentrations. We therefore conclude that the measurement of systemic sEGFR levels in addition to ECD serum concentrations do not allow the prediction of clinical course of trastuzumab-treated patients more accurately.
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PMID:Serum EGFR levels and efficacy of trastuzumab-based therapy in patients with metastatic breast cancer. 1632

Recently, clinical studies of new drugs development to target specific forms of cancer were reported. Herceptin, a monoclonal antibody against the Her2/neu receptor tyrosine kinase, prolonged the survival of women with Her2/neu positive metastatic breast cancer. STI571, a small molecule inhibitor of the BCR/ABL, c-Kit and platelet derived growth factor receptor tyrosine kinase, produced pronounced clinical responses in patients with BCR/ABL positive chronic myeloid leukemia and c-Kit positive gastrointestial stromal tumors. In order to consider the use of the inhibitor of tyrosine kinases activity as anticancer drug, their mechanisms of the oncogenic activation and their impact on tumor transformation should be studied. The treatment with tyrosine kinase inhibitors such as STI571 or herceptin was a spectacular clinical success which stimulated research on the structure and function of both kinases and their inhibitors.
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PMID:[Tyrosine kinases. New target of anticancer therapy]. 1638 Nov 69

Trastuzumab is the only HER2/neu-directed therapy to have received Food and Drug Administration approval for the treatment of patients with metastatic breast cancer. The efficacy of trastuzumab depends on the HER2/neu status of the tumour and the patient's prior treatment, but even when patients are selected on the basis of HER2/neu gene amplification, the single-agent response rate ranges from 12 to 30% and few patients respond to trastuzumab monotherapy. Here, we propose PTEN as a predictive biomarker for trastuzumab efficacy. Human breast cancer SKBR3 and drug-resistant SKBR3/R cells were investigated. We also examined clinical samples from patients who had been treated with trastuzumab and analysed the relationship between trastuzumab efficacy and PTEN level. The PI3K/Akt signalling pathway was observed to be highly active in the drug-resistant cells, and their level of PTEN was low. Delivery of antisense PTEN duplex siRNA significantly decreased the trastuzumab chemosensitivity of parental SKBR3 cells, and marked activation of Akt signalling pathway was also recognised. Moreover, immunohistochemical investigation revealed that trastuzumab treatment was remarkably successful in cells with elevated PTEN expression. Along with the immune-system-associated cytotoxic mechanism, several mechanisms have been proposed for the effect of trastuzumab. PTEN activity might play an important and major role in its HER2/PI3K/Akt-mediated antitumour effect, and could be a useful biomarker for predicting the efficacy of trastuzumab in the treatment of breast cancer.
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PMID:PTEN activity could be a predictive marker of trastuzumab efficacy in the treatment of ErbB2-overexpressing breast cancer. 1640 30


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