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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the past year there have been a number of important advances in the area of systemic therapy for breast cancer. Combined chemoendocrine therapy has been shown to be more effective than tamoxifen alone in the adjuvant therapy of node-negative estrogen receptor-positive breast cancer. Preliminary results of a randomized trial suggest that the addition of paclitaxel to adjuvant AC (Adriamycin and Cytoxan) improves survival in patients with operable node-positive disease. In the treatment of metastatic disease, preliminary results of a randomized trial have shown docetaxel to be superior to doxorubicin in response rate. In hormonal therapy, third generation aromatase inhibitors have replaced megestrol acetate as second-line hormonal therapy in receptor-positive disease. There are promising recent data about anti-HER-2 antibody therapy and other new approaches. This article reviews these and other recent advances in the systemic therapy of breast cancer.
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PMID:Recent advances in systemic therapy for breast cancer. 981 30

The goal of our study was to develop a panel of tumor cell lines along with paired non-malignant cell lines or strains collected from breast cancers, predominantly primary tumors. From a total of 189 breast tumor samples consisting of 177 primary tumors and 12 metastatic tissues, we established 21 human breast tumor cell lines that included 18 cell lines derived from primary tumors and 3 derived from metastatic lesions. Cell lines included those from patients with germline BRCA1 and FHIT gene mutations and others with possible genetic predisposition. For 19 tumor cell lines, we also established one or more corresponding non-malignant cell strains or B lymphoblastoid (BL) lines, which included 16 BL lines and 7 breast epithelial (2) or stromal (5) cell strains. The present report describes clinical, pathological and molecular information regarding the normal and tumor tissue sources along with relevant personal information and familial medical history. Analysis of the breast tumor cell lines indicated that most of the cell lines had the following features: they were derived from large tumors with or without axillary node metastases; were aneuploid and exhibited a moderate to poorly differentiated phenotype; were estrogen receptor (ER)- and progesterone receptor (PR)-negative; and overexpressed p53 and HER2/neu proteins. Of 13 patients with primary breast cancers receiving curative intent mastectomies, 7 were dead after a mean period of 10 months. Our panel of paired tumor and non-malignant cell lines should provide important new reagents for breast cancer research.
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PMID:Characterization of paired tumor and non-tumor cell lines established from patients with breast cancer. 983 71

Detecting and/or monitoring changes in circulating tumor markers might assist in evaluating cancer risk, diagnosis, prognosis, or response to treatment. Several categories of circulating tumor markers have been investigated in breast cancer. These categories include classical tumor-associated antigens, such as CEA and CA 15-3, markers of tumor biology, including markers of angiogenesis, adhesion, and invasion, and antibody response to tumor-associated antigens such as HER2/neu and p53. We used a recently proposed Tumor Marker Utility Grading System to evaluate the use of several circulating tumor markers for different clinical utilities in breast cancer. While there are no tumor markers with established clinical utilities for most uses, tumor-associated antigens can be used for monitoring patients with metastatic disease. In addition, markers of tumor biology such as the circulating extracellular domain of HER2/neu might be useful in determining not only prognosis, but also response to specific treatments. However, further investigations are required to further assess the utility of individual tumor markers for specific clinical uses.
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PMID:Circulating tumor markers in breast cancer: accepted utilities and novel prospects. 1006 86

Paclitaxel has emerged as an important agent in the treatment of breast cancer. The efficacy and tolerability of this agent, as well as its lack of cross-resistance with anthracyclines, have spurred intensive clinical investigation worldwide. Optimization of paclitaxel dose and scheduling and evaluation of the drug in combination regimens are a central focus of investigations. Recent clinical evidence suggests that optimal dose of single-agent paclitaxel by 3-h infusion is 175 mg/m². Trials evaluating administration schedule have not found either a 24-h or 96-h infusion to be superior to a 3-h infusion. Weekly moderate-dose paclitaxel administration is also generating much interest, given the high relative dose intensity and dose density delivered, yet very modest myelosuppression and manageable neurotoxicity observed. As first-line therapy in metastatic disease, multiple studies have documented overall response rates in the range of 30%-60%. As second-line or salvage single-agent therapy in metastatic patients, paclitaxel generally affords an overall response rate of 20%-40%, even in anthracycline-resistant patients. The novel mechanism of action and manageable toxicity of paclitaxel has led to successful incorporation into combination chemotherapy regimens. The combination of paclitaxel and doxorubicin has been the most extensively studied, with the role of this regimen continuing to evolve. Other combination regimens that appear to hold substantial promise as first-line metastatic treatment are paclitaxel with carboplatin and paclitaxel with trastuzumab (anti-HER2 antibody). The favorable results obtained in the metastatic setting have prompted phase II and phase III investigations of paclitaxel in the adjuvant and neoadjuvant settings. In the adjuvant setting, a recent phase III study has indicated that the addition of sequential paclitaxel to standard therapy affords both disease-free and overall survival benefits. Current investigations with paclitaxel will continue to optimize the role of this agent in the treatment of early- and advanced-stage breast cancer, addressing not only response rates but also survival and quality-of-life issues. The use of paclitaxel on a weekly schedule or with new therapeutic modalities, such as monoclonal antibodies, is also receiving much attention. While it is clear that paclitaxel is a very active agent in the treatment of breast cancer, it is hoped that these innovative trials will further maximize the potential of this agent in patients with breast cancer.
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PMID:Paclitaxel in Breast Cancer. 1038 29

The HER2/neu proto-oncogene is overexpressed in 25% to 30% of patients with breast cancer. Trastuzumab (Herceptin; Genentech, San Francisco, CA), a recombinant humanized monoclonal antibody with high affinity for the HER2 protein, inhibits the growth of breast cancer cells overexpressing HER2. In this phase II study the efficacy and toxicity of weekly administration of trastuzumab was evaluated in 46 patients with metastatic breast cancer whose tumors overexpressed HER2. A loading dose of 250 mg trastuzumab was administered intravenously, which was followed by 10 weekly doses of 100 mg each. Upon completion of this treatment period, patients with no disease progression could receive a weekly maintenance dose of 100 mg. Patients in this trial had extensive metastatic disease, and most had received prior anticancer therapy. Ninety percent of patients achieved adequate serum levels of trastuzumab. Toxicity was minimal, and no antibodies against trastuzumab could be detected. Objective responses were observed in 5 of the 43 evaluable patients, which included 1 complete remission and 4 partial remissions, for an overall response rate of 11.6%. Responses were seen in mediastinum, lymph nodes, liver, and chest wall lesions. Minor responses (seen in 2 patients) and stable disease (14 patients) lasted for a median of 5.1 months. These results demonstrate that trastuzumab is well tolerated and clinically active in patients with HER2-overexpressing metastatic breast cancers who have received extensive prior therapy. The regression of human cancer through the targeting of putative growth factor receptors such as HER2 warrants further evaluation of trastuzumab in the treatment of breast cancer.
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PMID:Phase II study of weekly intravenous trastuzumab (Herceptin) in patients with HER2/neu-overexpressing metastatic breast cancer. 1048 97

Several recent publications have re-opened the question of whether HER2 status should be determined for all patients with newly diagnosed breast cancer. The barrier in the past to the use of HER2 has been the nonstandardization of HER2 status determination, which is the major caveat to its use today. Two test kits have been recently approved by the Food and Drug Administration for HER2 testing, one for determining HER2 amplification by fluorescence in situ hybridization and the other for measuring HER2 overexpression by immunohistochemistry. Neither of these tests, nor any of the other myriad tests used for HER2 determinations, has been validated in all the potential arenas for the use of HER2: refinement of estimates of prognosis of untreated low-risk patients, selection among treatment options for adjuvant therapy, and selection of patients for treatment with trastuzumab (Herceptin; Genentech, San Francisco, CA). The nonstandardization of testing has led to conflicting results and controversy as to the value of HER2 in evaluating breast cancer patient prognosis and the selection among therapeutic options. Thus, testing for HER2 is not yet routine for patients with newly diagnosed breast cancer, although it is of value for patients who develop metastatic disease and who need to know if they are candidates for trastuzumab.
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PMID:Should HER2 status be routinely measured for all breast cancer patients? 1048 3

We conducted a phase I pharmacokinetic dose escalation study of a recombinant humanized anti-p185HER2 monoclonal antibody (MKC-454) in 18 patients with metastatic breast cancer refractory to chemotherapy. Three or six patients at each dose level received 1, 2, 4 and 8 mg kg(-1) of MKC-454 as 90-min intravenous infusions. The first dose was followed in 3 weeks by nine weekly doses. Target trough serum concentration has been set at 10 microg ml(-1) based on in vitro observations. The mean value of minimum trough serum concentrations at each dose level were 3.58 +/- 0.63, 6.53 +/- 5.26, 40.2 +/- 7.12 and 87.9 +/- 23.5 microg ml(-1) respectively. At 2 mg kg(-1), although minimum trough serum concentrations were lower than the target trough concentration with a wide range of variation, trough concentrations increased and exceeded the target concentration, as administrations were repeated weekly. Finally 2 mg kg(-1) was considered to be sufficient to achieve the target trough concentration by the weekly dosing regimen. One patient receiving 1 mg kg(-1) had grade 3 fever, one at the 1 mg kg(-1) level had severe fatigue defined as grade 3, and one at 8 mg kg(-1) had severe bone pain of grade 3. No antibodies against MKC-454 were detected in any patients. Objective tumour responses were observed in two patients; one receiving 4 mg kg(-1) had a partial response in lung metastases and the other receiving 8 mg kg(-1) had a complete response in soft tissue metastases. These results indicate that MKC-454 is well tolerated and effective in patients with refractory metastatic breast cancers overexpressing the HER2 proto-oncogene. Further evaluation of this agent with 2-4 mg kg(-1) weekly intravenous infusion is warranted.
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PMID:Dose escalation and pharmacokinetic study of a humanized anti-HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. 1060 42

We report on a rare distinctive variant of infiltrating ductal carcinoma characterized by sebaceous differentiation of tumor cells. The neoplasm was identified in a lumpectomy specimen from a 45-year-old woman with extensive metastatic disease. In addition to conventional in situ and invasive ductal components, approximately half of the tumor cells exhibited a phenotype resembling tumors of the sebaceous skin appendage with coarsely vacuolated cytoplasm and peripherally displaced nuclei. The sebaceous moiety was also present in the distant metastatic deposits. There was no evidence of mucin production by tumor cells. Ultrastructurally, empty-appearing non-membrane bound vacuoles attested to the sebaceous cells' lipid content. The immunoprofile of the lesion included positivity for cytokeratin and epithelial membrane antigen. Vimentin, S100 protein and carcinoembryonic antigen were not expressed. Most tumor cell nuclei reacted with antibodies to oestrogen and progesterone receptors but failed to show overexpression of the HER2/neu protein. The MIB-1 labeling index averaged 16%. At variance with sebaceous breast carcinomas on record, the present case is notable for its prolonged clinical course.
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PMID:Sebaceous carcinoma of the breast. 1069 80

We previously demonstrated that expression of the cell surface adhesion molecule MCAM/MUC18 correlates directly with the metastatic potential of human melanoma cells. In addition, the progression of human melanoma towards the metastatic phenotype is associated with loss of expression of the tyrosine-kinase receptor c-KIT. This review summarizes our recent data demonstrating that the expression of both genes is regulated by the AP-2 transcription factor. Moreover, we have observed a loss of AP-2 expression in metastatic melanoma cells. Re-expression of AP-2 in the highly metastatic A375SM cells decreased their tumorigenicity and inhibited their metastatic potential in nude mice. MCAM/MUC18 mRNA and protein expression was significantly downregulated while c-KIT expression was upregulated in the AP-2 transfected cells. Since AP-2 also regulates other genes that are involved in the progression of human melanoma such as E-cadherin, MMP-2, p21WAF-1, HER-2, BCL-2, and insulin like growth factor receptor-1, we propose that loss of AP-2 is a crucial event in the development of malignant melanoma.
Cancer Metastasis Rev 1999
PMID:Role of AP-2 in tumor growth and metastasis of human melanoma. 1072 91

Apart from the regulation of calcium metabolism, 1, 25-dihydroxyvitamin D(3) plays an essential role in cell proliferation and differentiation in several tissues. The vitamin D receptor (VDR) gene shows polymorphisms in humans that appear to be clinically significant in some pathological conditions. In the present study, the BsmI polymorphism of the VDR gene was studied in 59 Caucasian patients with rectal cancer (mean follow-up: 48 months). The relationship between VDR genotypes and the expression of oncogenes as well as their influence on survival were also investigated. VDR polymorphism was examined in tumor and normal mucosa cells by PCR technique. The expression of erbB-2/HER-2, p53, ras and epidermal growth factor receptor (EGFR) was also detected by immunohistochemistry and protein blotting. The presence of the VDR B allele significantly correlated with the overexpression of the erbB-2 oncogene. There was no difference in the VDR genotype between cancer and normal mucosal cells. Coexpression of erbB-2, pan-ras, p53 and EGFR internal and external domains was significantly higher in cancer cells than in normal mucosa. There was no significant correlation between VDR genotypes and age, gender, tumor infiltration depth, number and site of lymph node metastases and lymphatic or blood vessel infiltration. The VDR genotype alone did not influence survival. Overexpression of erbB-2 and EGFR was associated with a poor prognosis. In patients expressing only one oncogene in cancer cells, the presence of the VDR B allele showed a tendency to a poor prognosis. In conclusion, VDR gene BsmI polymorphism might affect the development and prognosis of rectal cancer by influencing erbB-2 oncogene expression.
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PMID:Vitamin D receptor gene BsmI polymorphism correlates with erbB-2/HER-2 expression in human rectal cancer. 1076 27


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