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)

This report analyzes clinical factors affecting outcome in 26 patients with inflammatory breast cancer. Peau d'orange was the most common clinical finding at diagnosis (65%). A palpable breast mass (PBM) was noted in 65% with axillary lymph node involvement in 81% of patients. Eighteen patients were staged as stage IIIB and eight as stage IV. Initial metastases included supraclavicular nodes (five of eight), bones (one of eight), skin (one of eight), and liver (one of eight). All patients were treated with neoadjuvant chemotherapy (cyclophosphamide, doxorubicin, and fluorouracil, 18 patients; other, 8 patients). Partial response was the best clinical response attained in 38% of patients. Only one patient was treated with total mastectomy after neoadjuvant chemotherapy, and 19 patients received radiotherapy followed (2 patients) or not (17 patients) by mastectomy. The progression rate in stage IIIB patients was 78%, with distant sites of progression in 93% of patients and only 7% with local progression. Mean time-to-progression was 13 months (Kaplan-Meier estimates of 45% and 11% at 24 and 48 months, respectively). The median overall survival (OS) value of the entire population was 13.2 months (Kaplan-Meier estimates at 24 and 48 months of 21% and 12.5%). By Kaplan-Meier method and log-rank test, a better OS was correlated with stage IIIB (p = 0.002), a PBM at diagnosis (p = 0.01), and a favorable response to initial chemotherapy (p = 0.03). Our results confirm the better clinical outcome of patients with stage IIIB and PBM at diagnosis. They also support the role for combined treatment as the best modality approach for this disease. However, overall prognosis remained poor, with recurrence and death resulting from the disease.
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PMID:Clinical outcome and prognosis of patients with inflammatory breast cancer. 1194 97

The use of primary or neoadjuvant chemotherapy for locally advanced breast cancer, including those patients with inflammatory breast cancer, is well established. The use of primary chemotherapy has also been investigated in patients with operable breast cancer. The potential benefit of using primary chemotherapy is the opportunity to administer systemic therapy at an earlier timepoint, where it may be more effective against microscopic disease. In addition, primary chemotherapy for patients with operable breast cancer may also result in higher rates of breast conservation, axillary nodal downstaging, and potential improvement in patient outcome. A variety of different chemotherapy drugs have been evaluated in the primary chemotherapy setting. One of the most common approaches is to use an anthracycline-based regimen for 4 or more cycles of treatment before considering definitive local therapy. Although high tumor response rates have been reported using anthracycline-based regimens, the fraction of patients actually attaining a pathologic complete response has remained small (less than 20%). With the introduction of new chemotherapy drugs, such as docetaxel, which is associated with a very high tumor response rate in metastatic disease, a natural evolution of clinical investigation is to use docetaxel in the neoadjuvant or primary chemotherapy setting. Some of the recent trials that have evaluated single-agent docetaxel, docetaxel-based chemotherapy combinations, and novel sequencing strategies that include docetaxel in the neoadjuvant setting are reviewed. The results from these trials clearly suggest that docetaxel-containing treatment strategies can be considered a standard in the primary chemotherapy setting
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PMID:Primary (neoadjuvant) chemotherapy with docetaxel in breast cancer. 1197 Jul 42

Inflammatory breast cancer (IBC) is the most lethal form of locally advanced breast cancer known. IBC carries a guarded prognosis primarily due to rapid onset of disease, typically within six months, and the propensity of tumor emboli to invade the dermal lymphatics and spread systemically. Although the clinical manifestations of IBC have been well documented, until recently little was known about the genetic mechanisms underlying the disease. In a comprehensive study aimed at identifying the molecular mechanisms responsible for the unique IBC phenotype, our laboratory identified overexpression of RhoC GTPase in over 90% of IBC tumors in contrast to 36% of stage-matched non-IBC tumors. We also demonstrated that overexpression of RhoC GTPase in human mammary epithelial (HME) cells nearly recapitulated the IBC phenotype with regards to invasion, motility and angiogenesis. In the current study we sought to delineate which signaling pathways were responsible for each aspect of the IBC phenotype. Using well-established inhibitors to the mitogen activated protein kinase (MAPK) and phosphatidylinositol-3 kinase (PI3K) pathways. We found that activation of the MAPK pathway was responsible for motility, invasion and production of angiogenic factors. In contrast, growth under anchorage independent conditions was dependent on the PI3K pathway.
Clin Exp Metastasis 2002
PMID:Mitogen activated protein kinase pathway is involved in RhoC GTPase induced motility, invasion and angiogenesis in inflammatory breast cancer. 1209 Apr 70

Tumors require a blood supply for growth and hematogenous metastases. Until recently, most research in this area has focused on the role of angiogenesis, the recruitment of new vessels into a tumor from preexisting vessels. Previously, in a study of breast cancer (IBC), in which we used established inflammatory breast cancer (IBC) xenografts (WIBC-9) originating from a patient with IBC (Shirakawa et al., Cancer Res 2001:61:445-451), we reported observing vasculogenic mimicry (VM), a condition in which bloodstreams within cancer tissue are not accompanied by a lining of endothelial cells (ECs) (Shirakawa et al., Cancer Res 2002:62:560-566). In the present study, we examined 331 surgically resected breast cancer specimens for evidence of VM, using immunohistochemistry and laser-captured microdissection (LCM) followed by nested reverse transcriptase polymerase chain reaction (RT-PCR). Surprisingly, 7.9% (26 specimens) of the 331 specimens exhibited evidence of VM. Of these 26 VM specimens, 84.6% (22 specimens) exhibited pseudo-comedo formation. RT-PCR analysis of 8 microdissected typical VM specimens revealed expression of Tie-2, Flt-1, thrombin receptor and CD31 in 63, 50, 0 and 0% of specimens, respectively. In contrast, results of RT-PCR analysis of 8 specimens from non-VM tumors were negative for expression of these genes. The 26 VM cases tended to have a higher percentage of hematogenous recurrence (p = 0.059) and a lower percentage of 5-year survival (p = 0.071) than the 305 non-VM cases. However, there were no significant differences in tumor size, lymph node metastasis, estrogen receptors or progesterone receptors between the 2 groups (p > 0.1). Our results suggest that the existence of VM increases the likelihood of hematogenous metastases and is in inverse proportion to prognosis.
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PMID:Vasculogenic mimicry and pseudo-comedo formation in breast cancer. 1211 83

The inflammatory breast cancer corresponds to 1-6% of breast tumors. It is an aggressive clinical entity being characterised by the incidence of local relapse and distant metastases superior to the other breast malign entities. Changes in its therapy have been observed: progressive innovating therapeutic strategies have been adopted, tendentiously multimodal ones, trying to alter the course of this pathology of such a unfavourable prognosis. Here we show a revision of the most significant facts in the evolution of the inflammatory breast carcinoma diagnosis and treatment, both as to the present development and future perspectives. Aspects of clinical diagnosis are emphasized as well as their corroboration with complementary diagnosis technics and their evolution before different approaching therapies.
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PMID:[Inflammatory breast cancer]. 1268 Feb 94

Inflammatory breast cancer (IBC) is the most aggressive form of locally advanced breast cancer. It can be diagnosed based on a clinical or pathologic basis. We evaluated the usefulness of (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scans for diagnosing and staging IBC. We retrospectively reviewed the medical records of seven consecutive patients with IBC who underwent FDG-PET scanning for the initial staging. Four patients had follow-up PET scans after chemotherapy. All seven patients presented with diffuse breast enlargement, redness, and peau d'orange for 1 to 5 months' duration. In addition, four patients had a palpable breast mass, and three had axillary lymph node enlargement. Mammography showed diffuse, increased parenchymal density and skin thickening in 85% and parenchymal distortion in 43%. There was no evidence of distant metastasis on computed tomography of the chest or abdomen. Pathologic examination of breast biopsy specimens showed infiltrating ductal carcinoma in six patients, and one had lobular carcinoma. All patients had prechemotherapy whole-body PET scans that showed diffuse FDG uptake in the breast with superimposed intense foci in the primary tumor. Furthermore, there was skin enhancement in 100%, axillary lymph node in 85%, and skeletal metastases in 14% of the patients, confirmed by bone scintigraphy. Postchemotherapy FDG-PET scans performed in four patients showed response in the primary tumor, axillary lymph nodes, and skeletal metastases. The FDG-PET scan is thus useful for displaying the pattern of FDG breast uptake that reflects the extent of the pathologic involvement in IBC (i.e., diffuse breast involvement and dermal lymphatic spread). It can also detect the presence of lymph node and skeletal metastases, demarcating the extent of the disease locally as well as distally.
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PMID:18-Fluorodeoxyglucose-positron emission tomography in inflammatory breast cancer. 1291 70

Trastuzumab/chemotherapy combinations have already shown superior results in metastatic breast cancer patients. The purpose of this study is to determine the clinical efficacy of neoadjuvant trastuzumab and docetaxel in women with locally advanced breast cancer, with or without metastatic disease. Treatment-naive women with HER2-overexpressing locally advanced breast cancer, with or without metastatic disease, were included. Patients received trastuzumab 4 mg/kg loading dose intravenously then 2 mg/kg weekly. On day 22, docetaxel 100 mg/m2 every 3 weeks for 4 cycles was added to weekly trastuzumab. Patients then underwent surgery and subsequent 4 cycles of AC (doxorubicin/cyclophosphamide; 60/600 mg/m2) without trastuzumab. Weekly trastuzumab was resumed 1 month after completion of AC and continued for a year. Preliminary results from the first 22 patients with median follow-up of 15.5 months (range, 2-38 months) are reported. Of these, 9 patients (40.9%) had inflammatory breast cancer, and 6 patients (27.3%) had stage IV breast cancer. Seventeen of 22 patients (77.3%) had objective clinical response, with a clinical complete response in 9 patients (40.9%). Two patients (9.1%) had decline in cardiac function and 7 patients (31.8%) experienced neutropenia, with 2 deaths (9.1%) from neutropenic sepsis. Eight patients (36.4%) have relapsed, 3 with local skin recurrence (13.6%) and 5 with distant recurrence, of whom 1 had liver metastasis (4.5%) and 4 had brain metastasis (18.2%). Combined neoadjuvant trastuzumab and docetaxel induced high clinical response rates for HER2-overexpressing breast cancer, in particular for inflammatory breast cancer. A high rate of brain metastasis was noted, particularly in patients with baseline metastatic disease.
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PMID:Neoadjuvant trastuzumab and docetaxel in breast cancer: preliminary results. 1471 10

Inflammatory breast cancer (IBC) is the most deadly form of breast cancer in humans presumably due to its ability to metastasize from its inception. In our laboratory, overexpression of RhoC GTPase was observed to be specific for IBC tumors, but not for stage-matched, non-IBC tumors. RhoC is known to contribute to an IBC-like phenotype in HPV-E6E7 immortalized breast cells. To further study the effect of RhoC overexpression on IBC metastasis, we generated stable transfectants of spontaneous immortalized mammary epithelial cells (MCF10A) overexpressing wild-type RhoC or a constitutively active RhoC mutant (G14V). Both the RhoC wild type and the G14V transfectants were highly invasive and proliferated more rapidly compared to vector-only control clones. Overexpression of RhoC led to an increase in actin stress fiber and focal adhesion contact formation. Comparative microarray analysis of these clones further revealed that RhoC overexpression upregulated 108 genes whereas seven genes were down-regulated. We have further verified by quantitative RT-PCR that genes involved in cell proliferation, invasion/adhesion, and angiogenesis were modulated by RhoC. This work suggests strong candidates for the downstream oncogenic functions of RhoC.
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PMID:RhoC induces differential expression of genes involved in invasion and metastasis in MCF10A breast cells. 1499 49

Occult breast cancer presenting with axillary lymph node metastases is uncommon, and inflammatory breast cancer (IBC), as a subtype, is quite rare. Here we describe a case of IBC, which arose as an unknown primary carcinoma; the patient presented with axillary lymph node metastasis, and was successfully treated with trastuzumab and vinorelbine. Specifically, a 55-year-old woman presented with right axillary lymphadenopathy. Although she underwent various examinations, the primary site of the disease was not revealed. Axillary lymph node dissection was performed, and the lesion was diagnosed as a poorly differentiated adenocarcinoma. The patient chose to be treated by alternative medicine. About 6 months later, she was referred to our hospital, due to marked bilateral neck and axillary lymph node swelling. She presented with diffuse right breast enlargement, redness, and peau d'orange. Computed tomography (CT) of the breast showed skin thickening and swelling of the right breast.F-18 Fluorodeoxyglucose positron emission tomography (FDG-PET) showed FDG uptake in the right breast. The patient was clinically diagnosed with IBC. Because overexpression of the human epidermal growth factor receptor 2 (HER2) was found in the specimen from her right axillary lymph node, she was treated with trastuzumab and vinorelbine. Two months after the start of chemotherapy, CT revealed a complete response in the lymph nodes, and the skin thickening and parenchymal edema of the right breast had improved. FDG-PET was also performed at this time, and revealed no FDG uptake in either the right breast or the lymph nodes.
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PMID:Unknown primary carcinoma, diagnosed as inflammatory breast cancer,and successfully treated with trastuzumab and vinorelbine. 1613 77

Inflammatory breast cancer (IBC) is an aggressive form of locally advanced breast cancer with high metastatic potential. Most patients have lymph node involvement at the time of diagnosis and 1/3 of the patients have distant metastases. In a previous study, we demonstrated that IBC is a distinct form of breast cancer in comparison with non-IBC. The aim of this study was to investigate the presence of the different molecular subtypes in our data set of 16 IBC and 18 non-IBC specimen. Therefore, we selected an 'intrinsic gene set' of 144 genes, present on our cDNA chips and common to the 'intrinsic gene set' described by Sorlie et al. [PNAS, 2003]. This set of genes was tested for performance in the Norway/Stanford data set by unsupervised hierarchical clustering. Expression centroids were then calculated for the core members of each of the five subclasses in the Norway/Stanford data set and used to classify our own specimens by calculating Spearman correlations between each sample and each centroid. We identified the same cell-of-origin subtypes in IBC as those already described in non-IBC. The classification was in good agreement with immunohistochemical data for estrogen receptor protein expression and cytokeratin 5/6 protein expression. Confirmation was done by an alternative unsupervised hierarchical clustering method. The robustness of this classification was assessed by an unsupervised hierarchical clustering with an alternative gene set of 141 genes related to the cell-of-origin subtypes, selected using a discriminating score and iterative random permutation testing. The contribution of the different cell-of-origin subtypes to the IBC phenotype was investigated by principal component analysis. Generally, the combined ErbB2-overexpressing and basal-like cluster was more expressed in IBC compared to non-IBC, whereas the combined luminal A, luminal B and normal-like cluster was more pronounced in non-IBC compared to IBC. The presence of the same molecular cell-of-origin subtypes in IBC as in non-IBC does not exclude the specific molecular nature of IBC, since gene lists that characterize IBC and non-IBC are entirely different from gene lists that define the different cell-of-origin subtypes, as evidenced by principal component analysis.
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PMID:Identification of cell-of-origin breast tumor subtypes in inflammatory breast cancer by gene expression profiling. 1626 4


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