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)

The overall median survival of women with advanced or high-risk primary breast cancer has not changed with conventional chemotherapy. Regimens employing high-dose chemotherapy with autologous stem cell support (ABMT) have been developed with the hope of optimizing tumor response and increasing survival. Early phase I studies in women with advanced refractory disease achieved high response rates of short duration. Second generation studies combined an induction phase followed by one high-dose intensification at time of maximum tumor response. The Dana-Farber Cancer Institute/Beth Israel Hospitals have developed the high-dose intensification regimen of cyclophosphamide, thiotepa, and carboplatin (CTCb) for use in women with metastatic and high-risk stage IIIB/inflammatory breast cancer. To date, approximately 19% of women with metastatic disease remain progression free using this approach, with median length of follow-up approaching 40 months. Although the median duration of follow-up for the stage IIIB women is much shorter (approximately 12 months), greater than 90% of these women are thus far disease free. With the advent of hematologic support, such as blood stem cells and colony-stimulating factors, the morbidity, mortality, and costs associated with this treatment have been substantially reduced, allowing for two or more cycles of high-dose intensification to be employed, to exploit the potential of dose-intensity to optimize response.
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PMID:High-dose chemotherapy with autologous stem cell support for breast cancer: a review of the Dana-Farber Cancer Institute/Beth Israel Hospital experience. 791 50

It is now accepted that c-erbB2-gene amplification is correlated with poor clinical outcome for patients, mainly when axillary nodes are invaded. We have confirmed this result by multivariate analysis in 178 patients with non-inflammatory breast cancer followed up for a mean period of 6.8 years (SD, 1.6 years). In addition, we have shown that c-erbB2 amplification, found in 30 (17%) specimens, was associated with a high risk of multiple metastases developing simultaneously. In contrast, for the 67 patients with inflammatory breast carcinoma, the most aggressive type of breast carcinoma, the c-erbB2 amplification detected in 24 (36%) specimens was not found to be associated with a higher risk of death, suggesting that the c-erbB2 gene plays a different role in the progression of these 2 types of breast cancer. Furthermore, our data stress the importance of the methodological approach used to determine gene amplification. Although Southern blot hybridization is a tumour- and time-consuming method not easy to adopt in routine clinical practice, this method remains a reference quantitative method.
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PMID:Association of c-erbB2-gene amplification with poor prognosis in non-inflammatory breast carcinomas but not in carcinomas of the inflammatory type. 792 65

This is a retrospective analysis of 50 patients with a minimum 2-year follow-up who had clinical signs and/or histologic evidence of inflammatory breast cancer and were treated with curative intent between October 1964 and March 1989. The 5-year relapse-free, absolute, and cause-specific survival rates for the overall group of 50 patients were 36, 39, and 45 per cent, respectively. Patients who received treatment with radiotherapy, chemotherapy, and surgery (n = 33) had a 5-year relapse-free survival rate of 50 per cent, compared with 7 per cent for those patients (n = 17) who received less treatment (P = 0.0002). The only clinical factor with a negative impact on relapse-free survival was mass size > 5 cm (P = 0.07). No advantage could be demonstrated for preoperative chemotherapy over postoperative chemotherapy or for doxorubicin-containing regimens over cyclophosphamide, methotrexate, and 5-fluorouracil. There was no difference in the incidence of distant metastases for patients receiving preoperative rather than postoperative chemotherapy, but there were more local recurrences in patients in whom local-regional treatment was delayed. A higher rate of arm edema was associated with more extensive surgery.
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PMID:Results of multimodality therapy for inflammatory breast cancer: an analysis of clinical and treatment factors affecting outcome. 811 87

Neoadjuvant (preoperative) chemotherapy (NACT) represents a novel approach based on sound theoretical, pharmacokinetic, and experimental principles. The purpose of NACT is to improve control of the primary site by stage reduction and/or to improve control of micro-metastatic disease. We showed in this paper that: 1) Intensive NACT is beneficial to most patients with infiltrative breast cancer. 2) The extent of surgery can be reduced by NACT, and may provide optimal local control with the possibility of breast conservation. 3) There is no evidence that cure or survival is altered by NACT, as compared with standard postoperative adjuvant therapy. 4) Evidence from all of these studies indicates the safety of NACT relative to overall systemic toxicity and local wound healing. In recent years, NACT has been tested in twelve patients with stage III and inflammatory breast cancer in our institute. The objective clinical response was as follows: complete response 0%, partial response 92%, no change 8%, progressive disease 0%. Projected disease-free survival was 51% and projected overall survival was 63% at 7 years. These reported results and our experience emphasize the important role of NACT in the management of breast cancer.
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PMID:[Neoadjuvant (preoperative) chemotherapy for resectable breast cancer]. 812 84

Between 1978 and 1987, 109 patients without metastatic disease were treated by induction chemotherapy for inflammatory breast cancer (IBC) or "neglected" locally advanced breast cancer (LABC): 62 patients had a clinical history of rapidly growing tumours (doubling time < or = 4 months) and inflammatory signs; conversely, the 47 neglected patients had local inflammation with a longer history of LABC. 103 patients were fully evaluable. All patients received the same induction chemotherapy with doxorubicin, vincristine, cyclophosphamide and 5-fluorouracil. After six cycles, locoregional treatment was by radiotherapy if a complete or nearly complete response had been obtained, and total mastectomy, with pre or postoperative radiotherapy, in other cases. The chemotherapy after local treatment comprised of six cycles for LABC and 12 cycles for IBC (six without doxorubicin). With a median follow-up of 120 months, the median overall survival (OS) time was 70 months as against 45 months for disease-free survival (DFS). No difference was observed for OS and DFS between LABC and IBC. The regional recurrence rate was 24% (15% for radiotherapy alone). 20 factors of potential prognostic significance were evaluated by univariate and multivariate analysis. For DFS and OS, univariate analysis suggested a worse prognostic significance for "peau d'orange" appearance of the skin, clinical evidence of node involvement and poor response to chemotherapy after three cycles, on mammographic criteria. The cumulative dose of doxorubicin after three cycles seemed to have a significant effect on OS (P < 0.03) but was too closely correlated with age to draw definite conclusions. In the multivariate analysis, "peau d'orange", menopausal status and clinical node involvement predicted DFS. "Peau d'orange" and clinical node involvement also predicted OS. Our results indicate that IBC and LABC do not behave differently when treated with our procedure.
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PMID:Treatment results, survival and prognostic factors in 109 inflammatory breast cancers: univariate and multivariate analysis. 851 16

Inflammatory breast cancer is an aggressive subtype of invasive breast cancer. Early attempts to control the disease with local treatment modalities alone had a minimal impact on survival. More recently, multimodality treatment approaches that integrate systemic chemotherapy, surgery, and radiotherapy have resulted in improved local disease control and prolonged survival. Better systemic therapies need to be developed since metastatic disease develops in the majority of patients.
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PMID:Inflammatory breast cancer: the evolution of multimodality treatment strategies. 887 24

Peripheral blood stem cells were mobilised with G-CSF from steady-state haemopoiesis after previous anthracyclin-containing standard dose chemotherapy in patients with high-risk breast cancer. 48 samples were obtained from patients with stage II-III breast cancer and > or = 10 lymph nodes, 15 samples from patients with chemotherapy sensitive metastatic disease, and 13 samples from women with inflammatory breast cancer. 44 samples were first or single leukaphereses and 32 samples were second or third harvests. Aliquots were searched for contaminating tumour cells by immunocytochemistry (IC) and cytokeratin-19 reverse transcriptase polymerase chain reaction rtPCR). The median count of MNCs examined by IC was 2 x 10(6); cDNA prepared from 2 x 10(7) cells was subjected to PCR. Fifty-nine samples were examined by immunocytochemistry, 36 samples by rtPCR, and 19 samples by both techniques. Samples investigated by IC and rtPCR were judged as positive if there was at least one positive test. On the whole, 42/79 (55.3%) of the samples were positive with an insignificant trend to a higher positivity rate in second or subsequent leukaphereses (52.3% vs 59.3%). The median tumour cell load per 10(6) MNCs was low with 0.5 (0-7) cells in all, and a total of 2.2 (0.5-7) cells in positive specimen. Differences in the cancer cell load of first and subsequent leukaphereses and between subgroups of patients were not found. PCR and IC gave consistent results in 63.2%. This phenomenon can be explained by the greater sensitivity of the molecular method and by a Poisson distribution of coharvested tumour cells in samples. Tumour cell contamination in G-CSF mobilised stem cells from patients with breast cancer from steady state haemopoiesis after preceding anthacyclin-containing chemotherapy is frequent, but the tumour cell load is low. To allow a comparison of different studies dealing with cancer cell contamination in stem cells, standardisation of assays is necessary.
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PMID:Tumour cell detection in G-CSF mobilised stem cell harvests of patients with breast cancer. 1038 38

We describe a case of unusual metastases of a gastric carcinoma to the female breast, there likely to be an inflammatory breast cancer. A 46-year-old woman was admitted to our institution with bilateral breast tumors, not typical for a breast cancer as tumor growth was synchronically bilateral within a very short period of only 2 months. The woman underwent a palliative gastrectomy 3 months before for a poorly differentiated adenocarcinoma with signet ring appearance presenting as linitis plastica. At the time of the first operation the mammary glands were not suspicious. Breast biopsies assured metastases of the gastric cancer. In addition to this case report, a short overview of the literature concerning the very few cases of metastases of gastric cancer to the breast is given.
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PMID:Metastasizing signet ring cell carcinoma of the stomach-mimicking bilateral inflammatory breast cancer. 1047 17

Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer (LABC) that effects approximately 5% of women with breast cancer annually in the USA. It is a clinically and pathologically distinct form of LABC that is particularly fast growing, invasive, and angiogenic. Nearly all women have lymph node involvement at the time of diagnosis, and approximately 36% have gross distant metastases. Despite recent advances in multimodality treatments, the prognosis of patients with IBC is poor, with a median disease-free survival of less than 2.5 years. Recent work on the genetic determinants that underlie the IBC phenotype has led to the identification of genes that are involved in the development and progression of this disease. This work has been aided by the establishment of primary human cell lines and animal models. These advances suggest novel targets for future interventions in the diagnosis and treatment of IBC.
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PMID:Molecular biology of breast cancer metastasis. Inflammatory breast cancer: clinical syndrome and molecular determinants. 1125 Jul 32

Based on in vitro and animals studies which assess dose effect relationship specially for alkylating agent, and on the importance on dose intensity in human protocols, high-dose chemotherapy with stem cell support has been widely evaluated in various tumours, particularly in breast cancer. Moreover, in the last few years, the utilization of hematopoietic growth factors and peripheral stem cells has permitted a large diffusion of this approach. However, there is not yet clear data on the place of such a treatment in breast cancer. Few randomized trials are available, with mature data. Only one shows an advantage for high-dose therapy in metastatic disease. In adjuvant setting, sample sizes are too small or follow-up not long enough to draw any definitive conclusion on the place of high-dose consolidation chemotherapy in breast cancer. In inflammatory breast cancer, which is a much more less frequent disease, encouraging results have been published in phase two studies, looking at pathological response, or in pilot studies. The next few years will give a mature date of randomized trials which evaluate high-dose chemotherapy given after conventional treatment in metastatic or high risk disease. Effort should be done to better evaluate this strategy in terms of cost and quality of life and to design new studies aimed to evaluate front line multiple intensification.
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PMID:High-dose chemotherapy in advanced breast cancer. 1185 90


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