Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Only a few cases on mucinous adenocarcinomas of the vulva have been reported. In this study, we present a case of a 75-year-old woman with a tumor in the left major labium. Because biopsy had shown formations of squamous cell carcinoma, radical vulvectomy with bilateral inguinal and femoral lymph node dissection were performed. At that time, histology was interpreted as small-cell, anaplastic carcinoma, with focal epidermoid differentiation. Postoperative radiation therapy was performed. Sixteen months after surgery, the patient presented with bilateral breast carcinomas. Histology showed a scirrhous carcinoma of the left and a medullary carcinoma of the right breast, but no lymph node metastases. Histochemical and immunohistochemical re-examination of the vulvar carcinoma now revealed a mucinous adenocarcinoma with neuroendocrine differentiation. The tumor expressed neuroendocrine markers such as chromogranin A and protein gene-product (PGP) 9.5, as well as peptides of the vasoactive intestinal polypeptide (VIP) family, and serotonin. Histochemical silver stains demonstrated Grimelius argyrophilia and Masson argentaffinity. Because of positive estrogen and progesterone receptor status of both breast cancers, postoperative Tamoxifen therapy was performed. The patient is still alive four years after vulvectomy.
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PMID:Primary neuroendocrine differentiated mucinous adenocarcinoma of the vulva: case report and review of the literature. 967 64

Extensive clinical experience, summarised in the recent overview of the Early Breast Cancer Trialists' Collaborative Group (EBCTCG), have confirmed that tamoxifen reduces the rate of both disease recurrence and mortality when administered as adjuvant therapy in women with early breast cancer. Tamoxifen is now established as the preferred adjuvant agent in postmenopausal women; in particular, patients with node-positive, estrogen receptor-positive breast cancer have the most to gain from tamoxifen therapy. Data from a decision-analysis model indicated that tamoxifen monotherapy had a cost-utility ration {$US6000 per additional quality-adjusted life-year (QALY), in 1989 dollars} 5 to 6 times lower than that cited as the cost-acceptability cut-off point in the US. While tamoxifen monotherapy is effective in postmenopausal women, the EBCTCG overview findings indicate that a combined regimen of tamoxifen and antineoplastic chemotherapy has superior efficacy in the same patient group. An issue of current interest is whether the added benefit offered by such a regimen can be justified in terms of added toxicity and cost. Data from a decision-analysis model indicate that combined therapy has a high incremental cost-utility ratio ($US58 000 per additional QALY, in 1989 dollars) compared with no therapy in postmenopausal women. However, the quality-of-life measures TWiST (Time Without Symptoms and Toxicity) and Q-TWiST (quality-adjusted TWiST) indicate that the early toxicity associated with a combined regimen appears to be justified given the superior long term benefits. Patient preference data from 1 study further indicate that the degree of benefit offered by a combined regimen would be acceptable to the majority (73%) of patients. Other areas where pharmacoeconomic analyses may help define more closely the optimal use of adjuvant tamoxifen is in patients at low risk of developing metastatic disease and in determining the optimal duration of therapy. Both areas require further clinical data. In conclusion, tamoxifen adjuvant monotherapy has a low cost-utility ratio in postmenopausal women with node-positive, estrogen receptor-positive breast cancer. Combined therapy in the same patient group has a high cost-utility ratio compared with no therapy but quality-of-life and patient preference data suggest that the costs may be justified. Firm conclusions relating to the use of the drug in other patient subgroups and the optimal duration of therapy await further research.
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PMID:Tamoxifen: a review of pharmacoeconomic and quality-of-life considerations for its use as adjuvant therapy in women with breast cancer. 1014 67

Recent trials comparing single-agent vs combination therapy in metastatic breast cancer suggest that it may be time to reconsider the belief that combination chemotherapy is the gold standard of treatment. Based on the limited randomized trial data available to date, high-dose chemotherapy with stem-cell rescue should not be viewed as "state-of-the art" treatment for metastatic disease and should be used only in the context of clinical trials. Recent trials have explored the optimal dosing and scheduling of the taxanes, as well as the possible role of these agents in combination regimens. Capecitabine (Xeloda), a new oral fluoropyrimidine, appears to be comparable in efficacy to CMF (cyclophosphamide, methotrexate, and fluorouracil), and preclinical data suggest possible synergy between this agent and the taxanes. Other promising agents under study include liposome-encapsulated doxorubicin (TLCD-99), an immunoconjugate linking a chimeric human/mouse monoclonal antibody to doxorubicin molecules; MTA (LY231514), a multitargeted antifolate; and marimistat, a broad-spectrum matrix metalloproteinase inhibitor. Tamoxifen (Nolvadex) remains the most important hormonal agent, but new antiestrogens and selective estrogen receptor modulators (SERMs) may provide alternatives. The potential role of new aromatase inhibitors as first-line hormonal agents requires further study. Finally, the possible synergy between trastuzumab (Herceptin), a recombinant humanized monoclonal antibody to the HER-2/neu protein, and paclitaxel (Taxol) is being studied in two clinical trials.
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PMID:Update on the management of advanced breast cancer. 1035 85

Breast cancer cells can metastasize early in the development of primary tumors. Adjuvant chemotherapy improves disease-free survival and overall survival (OS) in patients with early-stage breast cancer, both in premenopausal and postmenopausal women. Tamoxifen improves OS in patients whose tumors are estrogen-receptor-positive, regardless of age. Although the relative risk reduction with these interventions is the same for all patients, the absolute benefit is more prominent in patients at the highest risk of relapse. All patients with involved lymph nodes should receive adjuvant chemotherapy if no contraindications occur. In patients with negative lymph nodes, adjuvant chemotherapy is recommended if the invasive tumor is moderately or poorly differentiated, the tumor size is larger than 1 or 2 cm, or hormone receptors are negative. Other prognostic and predictive indicators of response to chemotherapy and hormonal therapy remain investigational. Models that combine several factors to determine a patient's risk of relapse and death are presented. Neoadjuvant chemotherapy in conjunction with radiation therapy and surgery is the treatment of choice for patients with locally advanced breast cancer. Recently, this approach has been extended to patients with small, operable tumors. Neoadjuvant chemotherapy can downstage tumors effectively, leading to improved cosmetic results and possibly to a reduction in local recurrence rate. Another advantage of neoadjuvant therapy is the in vivo assessment of tumor sensitivity to chemotherapy, which allows optimization of available therapeutic agents. One disadvantage of neoadjuvant chemotherapy is that preoperative treatment causes an alteration of information regarding lymph node status prior to systemic treatment. Although the optimal chemotherapy regimen has not been established, doxorubicin-containing regimens are considered superior to non-doxorubicin-containing regimens. The role of high-dose chemotherapy is not well defined in the adjuvant setting and remains investigational. The taxanes paclitaxel and docetaxel are moving rapidly from the metastatic setting to the adjuvant setting. A better understanding of the biology of breast cancer is providing molecular tools to study novel treatment approaches. Oncogenes and tumor suppressor genes are emerging as important indicators of response to chemotherapy. These molecules, in turn, become targets for therapy. Novel agents under development are presented.
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PMID:Integration of Systemic Chemotherapy in the Management of Primary Breast Cancer. 1038 20

Two cases of metastatic breast cancer are reported in which endocrine chemotherapy with Toremifene + 5'-DFUR proved markedly effective. Case 1: A 69-year-old female. After CAF therapy as a adjuvant chemotherapy, Tamoxifen and Tegafur had been administered. At the 5th postoperative year, multiple metastases to lung and a rise in the tumor marker were found. Since the patient was not desirous of intensive chemotherapy, administration of Toremifene 120 mg/day and 5'-DFUR 800 mg/day was initiated. The patient showed PR 9 months after and achieved CR 14 months later. Case 2: A 48-year-old female. CAF therapy for a total of 6 cycles was performed as adjuvant chemotherapy. The patient was administered Tamoxifen and followed. On bone scintigrams 3.5 years after surgery, an abnormal accumulation appeared in the left sternoclavicular joint, and an infiltrative tumor mass was formed in the skin of that region. Administration of Toremifene + 5'-DFUR was initiated. After 6 months, the infiltrative mass disappeared. These findings are suggestive of the effectiveness of this combined chemotherapy.
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PMID:[Endocrine chemotherapy (high-dose toremifene + 5'-DFUR) found markedly effective for 2 cases of metastatic breast cancer]. 1039 29

Hepatocellular carcinoma (HCC) is a common, potentially lethal tumor in human patients. Because the serum levels of transforming growth factor-beta1 (TGF-beta1) correlate with outcome in patients with HCC and because TGFbeta1 mRNA expression is increased in HCC tissues, it raises the possibility that TGF-beta1 may be of importance in the development, growth, and metastases of HCC. Tamoxifen has been used for the treatment of human HCC. However, clinical trials have produced conflicting results. To further delineate whether tamoxifen may be of benefit in altering the course of HCC, we documented the effects of 4-hydroxytamoxifen and 17beta-estradiol on TGF-beta1 mRNA and protein levels and cell proliferation in a human HCC cell line. PLC/PRF/5 cells were treated with carrier (controls), 4-hydroxytamoxifen, 17beta-estradiol, or TGF-beta1. 4-Hydroxytamoxifen and 17beta-estradiol decreased TGF-beta1 mRNA and protein levels in a time- and dose-dependent manner. TGF-beta1 significantly inhibited PLC/PRF/5 cell proliferation, whereas both 4-hydroxytamoxifen and 17beta-estradiol stimulated PLC/PRF/5 cell proliferation. The stimulatory effects of 4-hydroxytamoxifen on PLC/PRF/5 cell proliferation raise concerns regarding its use in the treatment of HCC in human patients and suggest that 4-hydroxytamoxifen may have no beneficial effects in some patients with HCC.
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PMID:Regulation of transforming growth factor-beta1 gene expression and cell proliferation in human hepatocellular carcinoma cells (PLC/PRF/5) by tamoxifen. 1040 64

Fibroepithelial stromal polyps of the vulvovaginal region are benign lesions that, when bland or hypocellular, are readily recognized. However those that exhibit bizarre cytomorphology, atypical mitoses, or hypercellularity, raising the possibility of malignancy, continue to be underrecognized. The authors reviewed a series of fibroepithelial stromal polyps to characterize further the morphologic features that can lead to a misdiagnosis of sarcoma. A total of 33 of 65 consecutive cases of fibroepithelial stromal polyps retrieved from the authors' consultation files were remarkable for marked hypercellularity (33 of 33), marked cytologic pleomorphism (21 of 33), mitotic counts of more than 10 mitoses per 10 high-power fields (12 of 33), and the presence of atypical mitoses (14 of 33). A total of 16 of 33 lesions had three or more of these features. Important morphologic clues to the diagnosis (shared with usual polyps at this site) were lack of an identifiable lesional margin, extension of abnormal stromal tissue up to the mucosal-submucosal interface, and the frequent presence of individually scattered multinucleate stromal cells, most often located close to the surface epithelium. Immunohistochemically, seven of 12 cases were desmin positive and one of 11 cases were smooth muscle actin positive. The age range of patients was 16 to 75 years (median, 32 years), and 21 patients (64%) were premenopausal. Sites included the vagina (18 of 33), cervix (seven of 33), and vulva (eight of 33). A total of 14 of 33 patients were pregnant, three patients were taking Tamoxifen, and one patient was on oral progesterone. Eight of 33 patients had multiple lesions at the time of presentation, of whom five were pregnant. Clinical follow-up was available in 21 of 33 patients. Three of 21 patients with follow-up had local, nondestructive recurrence. Two of these patients had multiple recurrences. None of the patients followed developed metastases. Cytologic atypia has been a previously recognized feature in these lesions; however, the occurrence of marked stromal cellularity and a mitotic rate of more than 10 mitoses per 10 high-power fields have not been emphasized previously. Moreover, the combination of these features has only rarely been documented. Awareness of the spectrum of histologic features that these lesions can exhibit is crucial in their accurate recognition, thus avoiding potential overtreatment.
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PMID:Cellular pseudosarcomatous fibroepithelial stromal polyps of the lower female genital tract: an underrecognized lesion often misdiagnosed as sarcoma. 1068 Aug 91

This commentary evaluates progress made in the treatment of breast cancer during the twentieth century. Most of the period from 1900 to 1970 was governed by the 'non-science' of anecdotalism and classical inductivism and was marked by the absence of a scientific gestalt. In keeping with the Halstedian concept that breast cancer was a local disease that spread throughout the body by contiguous extension and could be cured by more expansive surgery, the disease was treated with radical surgery. In 1950, however, a new era of enlightenment began to emerge. The awareness that there was a scientific process in which hypotheses generated from laboratory and clinical investigation could be tested by means of randomised clinical trials was a seminal advance, as were findings from studies that laid the groundwork for the modern era of steroid hormone action, including identification of oestrogen receptors. Expanding knowledge regarding tumour cell kinetics, tumour heterogeneity, and technological advances related to mammography and radiation therapy were also to play a role in making possible the advances in therapy that were subsequently to occur. In the past 30 years, as a result of laboratory and clinical investigation, the Halstedian thesis of cancer surgery was displaced by an alternative hypothesis that was supported by findings from subsequent clinical trials. A new paradigm governed surgery for breast cancer, and lumpectomy followed by radiation therapy became accepted practice. A second paradigm that governed the use of adjuvant systemic therapy arose as a result of laboratory and clinical investigation. Treating patients who were free of identifiable metastatic disease with systemic adjuvant therapy because some of them might develop distant disease in the future was a revolutionary departure from prior treatment strategy and became a new exemplar. Not only did the chemotherapy favourably alter the outcome of breast cancer patients, but the anti-oestrogen tamoxifen benefited patients with all stages of the disease. Tamoxifen also reduced the incidence of contralateral breast cancer, as well as tumour in the ipsilateral breast following lumpectomy. The use of preoperative therapy was also found to enhance breast-conserving surgery in women with large tumours, although its value in other circumstances is still being defined. The observation that, as a result of tamoxifen administration, invasive and non-invasive breast cancers can be prevented in women who are at increased risk for such tumours, and the finding that pathological entities such as atypical hyperplasia, lobular carcinoma in situ (LCIS) and intraductal carcinoma (DCIS) can identify women who should be considered candidates for tamoxifen serve as a fitting capstone to the accomplishments of the twentieth century. Breast cancer prevention has now become a reality. Unfortunately, a variety of circumstances have arisen as the result of advances in the understanding and treatment of breast cancer over the last 30 years that threaten to nullify the progress that has been achieved. This distressing phenomenon may be reviewed as a 'paradox of accomplishment'. The numerous uncertainties, issues and questions that have arisen following the report of each advance in treatment, the surfeit of new information that has not yet been integrated into treatment strategies, the undesirable consequences of enhanced tumour detection, a reversion to Halstedianism and anecdotalism, and the uncertainty of therapeutic decision making resulting from the demonstration of small but statistically significant benefits, particularly in patients with good prognosis, need to be addressed. Inappropriate interpretation of those circumstances threatens to deny women with breast cancer and those at high risk for the disease the opportunity to benefit from treatments that have been proven to be of worth. Perhaps the most important accomplishment of the twentieth century relates to the change in the pro
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PMID:From Halsted to prevention and beyond: advances in the management of breast cancer during the twentieth century. 1071 Dec 39

Liarozole is an imidazole compound that inhibits enzymes involved in steroid hormone aromatisation and retinoid metabolism. The IDBBC branch of the EORTC has performed a series of phase II studies of the agent in four groups of postmenopausal women with metastatic breast cancer. This paper reports the results of the first two groups: 'Chemotherapy Resistant' (unrestricted ER status, 1 or 2 prior chemotherapy regimens, 0-2 prior hormonal therapies) and 'Potentially Hormone Sensitive' (ER positive or unknown, 1 or 2 prior hormonal therapies with a substantial disease free interval or progression free survival, and no history of chemotherapy for metastatic disease). Liarozole was administered at 150-300 mg orally bid. The objective response rate was 12% in the 'Chemotherapy Resistant' group (n = 34), and 22% in the 'Potentially Hormone Sensitive' group (n = 37), with median response durations of 9 and 14 months, respectively. Median time to treatment failure was only 2 months in both groups, due largely to the significant percentage (24%) of patients who ceased treatment following excessive mucocutaneous and gastrointestinal toxicity. This adverse event profile will limit its use in breast cancer. Results of the 'ER negative' and 'Tamoxifen Refractory' groups will be reported in a future paper.
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PMID:EORTC 10941: A phase II study of liarozole in postmenopausal patients with 'chemotherapy-resistant' or 'potentially hormone sensitive' metastatic breast cancer. 1084 81

The assessment of angiogenesis in breast cancer is of importance as a key indicator of survival and response to therapy. Circulating vascular endothelial growth factor (VEGF) measurements may provide a less subjective analysis than microvessel density (MVD) or immunohistochemical analysis of VEGF expression; however, most studies have used serum, which is now known to largely reflect platelet-derived VEGF concentrations. This study examined for the first time both plasma (VEGFp) and serum (VEGFs) VEGF concentrations in 201 blood samples from pre- and postmenopausal healthy controls and from patients with benign breast disease, localized breast cancer, breast cancer in remission, or metastatic breast cancer and related these to other clinicopathological markers. VEGFp but not VEGFs concentrations of patients with localized disease were significantly elevated compared with normal controls (P = 0.016). Patients with metastatic disease had higher VEGFp and VEGFs levels than normal controls (P < 0.001, P = 0.044 respectively), and higher VEGFp, but not VEGFs, than patients with benign disease (P = 0.009) and patients with localized disease (P = 0.004). However, the highest VEGFp and VEGFs concentrations were seen in patients in remission compared with normal controls (P < 0.001 and P = 0.008, respectively). VEGFp concentrations in patients in remission were also higher than in patients with benign disease (P = 0.01) or patients with localized disease (P = 0.005). Tamoxifen treatment was significantly associated with higher circulating and platelet-derived VEGF levels. Circulating VEGF did not correlate with any clinicopathological factor, including MVD or VEGF expression. VEGF expression was significantly correlated with estrogen receptor status and inversely correlated with tumor grade. MVD correlated with tumor size. Tamoxifen-induced increases in VEGF may be important in clinical prognosis or associated pathologies.
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PMID:Vascular endothelial growth factor (VEGF) in breast cancer: comparison of plasma, serum, and tissue VEGF and microvessel density and effects of tamoxifen. 1085 Apr 35


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