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

In a group of 161 patients with operable cancer of the breast, tumour size, axillary node status and histopathological grading were correlated. Furthermore, steroid hormone receptor status was assessed both biochemically and immunohistochemically. The rate of Ki67-positive cells, the ploidy status and the S-phase fraction of the carcinoma, as assessed by means of flow-cytometry, were measured and correlated with tumour size and conventional histopathological grading. As expected, a significant correlation between tumour size and the frequency of axillary lymph node metastases was found (p < 0.00001). There was however, also a significant increase of undifferentiated cancers with increasing tumour size (p < 0.001). There was no correlation between steroid hormone receptor expression and grading but a slight decrease of immunohistochemically oestrogen receptor positive cancers with increasing tumour size (p < 0.02). On the other hand, there was a marked increase of both Ki67-score (p < 0.003) and S-phase fraction (p < 0.001) with increasing tumour size. Neither of the first two parameters correlated significantly with grading. The frequency of aneuploid tumours was dependent on tumour size (p < 0.05) as well as grading (p < 0.01). The findings point towards a change of biological properties of the cancer during the course of growth, such as histopathological dedifferentiation and increased proliferation fraction and frequency of aneuploid tumours. The expression of steroid hormone receptors however is virtually unchanged.
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PMID:Breast cancer and prognostic factors. Tumour size, degree of differentiation, proliferation kinetics and expression of steroid hormone receptors. 787 57

In a retrospective study, paraffin-embedded tissues from 110 primary T1 breast carcinomas (tumour diameter < or = 2 cm) were examined for the presence of the Her-2/neu encoded oncoprotein p185neu, using an immunohistochemical technique. Primary surgical therapy revealed no node involvement in 76 cases. These patients did not receive an adjuvant systemic therapy. 25% of tumours were positive for p185neu. Expression of the oncoprotein was inversely correlated to oestrogen receptor status (p < 0.05). In patients with lymph node metastases and poorly differentiated tumours, the incidence of p185neu was higher than in node negative and/or well differentiated carcinomas. However, this finding was statistically not significant. No correlations were found between the detection of the oncoprotein and age, menopausal and progesterone receptor status. The median follow-up is 85 months. In patients without lymph node metastases (n = 76), presence of the oncoprotein was significantly correlated to a shorter relapse-free and/or overall survival (p < 0.05). No such correlation was found for 34 patients with lymph node involvement. Expression of p185neu seems to mark a group of T1N0 breast cancer patients, which is at high risk and might benefit from an adjuvant therapy.
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PMID:[Expression of the p185neu oncoprotein indicates an unfavorable prognosis in small, node negative breast cancer without systemic adjuvant treatment (T1N0)]. 790 Nov 11

A number of endocrine treatments for advanced breast cancer seem to affect serum insulin-like growth factor I (IGF-I). The aim of our study was to investigate IGF-I levels in 33 postmenopausal patients with metastatic disease receiving the selective aromatase inhibitor 4-hydroxyandrostenedione: 250 mg (16 patients) or 500 mg (17 patients) i.m. fortnightly. Blood samples were collected before, and at one month and 3 months after the beginning of treatment for radioimmunoassay determinations. The median patient age was 56 and 60 years in the 250 and 500 mg groups respectively. Most patients had a disease free interval > or = 2 years and were oestrogen receptor positive. Objective responses were obtained in 3 patients (complete response, 1) in the 250 mg group, and in 7 patients (complete response, 3) in the 500 mg group. No significant IGF-I variations were seen in the 250 mg group, whereas a significant increase after 3 months (181.57 +/- 84.78 ng/ml versus 272.47 +/- 213.22 ng/ml, p = 0.0032) was observed in the 500 mg group. No IGF-I variations were seen between responsive and unresponsive patients in either treatment group. Our results in the 500 mg group are close to those obtained with aminoglutethimide and seem to agree with the hypothesis of an oestrogen-induced suppression of IGF-I circulating levels.
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PMID:Effect of two-4-hydroxyandrostenedione doses on serum insulin-like growth factor I levels in advanced breast cancer. 794 10

Cancer chemotherapy interacts with cell proliferation, but data on the relationship between cancer cell replication and the effect of adjuvant chemotherapy are scarce. We have investigated the S-phase fractions of the primary tumour from premenopausal breast cancer patients who participated in a randomised trial comparing 12 cycles of polychemotherapy (CMF) with post-operative radiotherapy. DNA flow cytometry was performed on frozen tissues from 208 primary breast carcinomas, of which the S-phase fraction was estimated in 176 cases. There was a significantly higher benefit from CMF among patients with a high S-phase fraction (P = 0.0033). The relative risk of distant recurrence or death in the chemotherapy group as compared with the radiotherapy group was 0.19 for patients whose tumours had an S-phase fraction of 10% or over (95% CI 0.07-0.51) and 1.55 (0.88-2.73) for patients whose tumours showed lower S-phase levels. The interaction was still significant in multivariate analysis (P = 0.0057), including lymph node metastases, tumour size and oestrogen receptor content. We conclude that the benefit from adjuvant chemotherapy compared with radiotherapy is largely confined to patients with highly proliferative tumours.
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PMID:S-phase fraction and survival benefit from adjuvant chemotherapy or radiotherapy of breast cancer. 798 Oct 85

The biological features of tumour type, histological grade, vascular invasion, mitotic index, DNA index, and oestrogen receptor (ER) and progesterone receptor (PgR) status have been investigated as prognostic factors in primary operable breast cancer. We have studied these 7 factors in locally advanced primary breast cancer (LAPC): these patients have occult metastases at presentation. Of 60 consecutive patients presenting with locally advanced disease, 36 were treated initially with Tamoxifen and 24 by radiotherapy. Treatment failure was followed by cross-over to the other therapy. All patients were assessed for response in the primary tumour; external review of response was obtained. Survival was compared using the generalised Wilcoxon test. Response to therapy correlated significantly with histological grade (p = 0.02), ER (p = 0.02), PgR status (p = 0.02), mitotic index (p = 0.01), and tumour ploidy (p = 0.04). Survival from initial therapy correlated significantly with ER (p = 0.01) and PgR status (p = 0.04). Histological grade, mitotic index, tumour ploidy, and ER and PgR status of the primary tumour predict response and prognosis in patients with locally advanced (stage III) breast cancer.
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PMID:Biological factors of prognostic significance in locally advanced breast cancer. 804 59

Constant denaturant gel electrophoresis (CDGE) was used to screen 179 breast carcinomas for mutations in the conserved regions of the TP53 gene (exons 5 through 8). Mutations were found in 35 of 163 primary tumours (21%) and in 5 of 16 metastases (31%) and resided predominantly in exon 7. The majority of the mutations were G:C-->A:T transitions. Immunohistochemistry demonstrated nuclear accumulation of p53 protein in 35 of 162 primary tumours (22%) and in four of 15 metastases (27%). TP53 mutation was strongly associated with nuclear accumulation of p53 protein. In total 42 of 163 primary tumours (26%) and 5 of 16 metastases (31%) were demonstrated to contain TP53 alterations (mutation and/or nuclear protein accumulation). TP53 alteration in primary tumour was significantly associated with the following parameters: positive node status, T status > 1, negative oestrogen receptor status, negative progesterone receptor status, presence of ERBB2 gene amplification, and invasive ductal histology. Furthermore, there were statistically significant associations, independent of other prognostic factors, between TP53 alterations in primary tumour and disease-free and overall survival.
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PMID:Prognostic significance of TP53 alterations in breast carcinoma. 810 35

Using the Boyden chamber invasion assay, the effect of 1 alpha,25-dihydroxyvitamin D3 [1 apha,25(OH)2D3] on the invasiveness of the highly invasive, oestrogen receptor-negative human breast cancer cell line MDA-MB-231 was examined. The MDA-MB-231 cells were shown to contain high-affinity receptors for 1 alpha,25(OH)2D3 with a Kd of 1.5 x 10(-11) M. When the cells were treated with 1 alpha,25(OH)2D3 for 4 days before the assay was performed, a dose-dependent inhibition of their invasive potential was demonstrated. Fifty per cent inhibition of invasion was obtained with a concentration of 13 pM of 1 alpha,25(OH)2D3. However, when the cells were treated for only 6 h during the assay, no inhibitory effect was seen. The process of migration was also affected by treatment with 1 alpha,25(OH)2D3 for 4 days, although the inhibition was not of the same magnitude as seen for the invasion. Fifty per cent inhibition of migration occurred at a concentration of 3.2 nM of 1 alpha,25(OH)2D3 (250 times higher than in the invasion assay). Inhibition of invasion and migration was not due to the known anti-proliferative effect of 1 alpha,25(OH)2D3, as no growth reduction could be demonstrated with treatment up to 5 days. Based on the present investigation it can therefore be concluded that 1 alpha,25(OH)2D3 is able to inhibit tumour cell invasiveness by a mechanism which is not exclusively based on its anti-proliferative and anti-migrative effects.
Clin Exp Metastasis 1994 May
PMID:1 alpha,25-Dihydroxyvitamin D3 inhibits the invasive potential of human breast cancer cells in vitro. 819 94

Plasminogen activator (PA) is a serine protease existing in two forms known as tissue-type (t-PA) and urokinase-type (u-PA). To examine whether PA is related to the postoperative clinical course of human breast cancer, total PA activity, t-PA activity, u-PA activity, and immunoreactive t-PA were determined in tissue extracts from 144 breast cancer specimens. The patients were initially divided into four groups according to the postoperative clinical course: Group I (83 patients who are disease-free), Group II (20 patients whose first metastases were found only in bone), Group III (19 patients whose first metastases were found in both bone and lung), and Group IV (22 patients whose first metastases were found only in lung). Total PA activity was significantly lower in Groups, II, III and IV than in Group I. Both t-PA activity and t-PA antigen levels were also significantly lower in Groups II, III and IV than in Group I, while no significant difference was found in u-PA activity among these groups, indicating that low activity of total PA in Groups II, III and IV was due to a decrease in t-PA but not in u-PA. In the multivariate analyses, t-PA activity was found to be an independent prognostic factor for relapse-free survival. When four groups of patients were further analysed in terms of nodal status, both t-PA activity and antigen levels were markedly decreased in the node-negative Group II compared with the node-negative Groups III and IV or with the node-positive Groups II, III and IV. Of additional interest, u-PA activity was significantly higher in node-positive patients than in node-negative patients with any group. The clinico-pathologic analyses of the patients in this series showed that node involvement and lymphatic invasion were more frequently positive in Groups III and IV than in Groups I and II. When 144 breast cancers were categorised in terms of combinations of oestrogen receptor (ER) and progesterone receptor (PgR) status, breast cancers which were positive for both receptors were found to contain the highest t-PA activity and antigen. This study provides provocative evidence suggesting a possible differential significance of t-PA and u-PA expression in human breast cancer.
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PMID:Differential biological significance of tissue-type and urokinase-type plasminogen activator in human breast cancer. 839 31

By application of a monoclonal antibody (Abbott ER-ICA) oestrogen receptors can now be demonstrated and semiquantitated on paraffin sections after fixation in formalin. In a prospective series of 22 breast carcinomas we found that 82% (18/22) were oestrogen receptor positive. The frequency was significantly lower in archival tissue comprising 27 invasive carcinomas (56%) and in 63 intraductal carcinomas (54%). Even lower frequencies were found in recurrences and metastases and none (0/10) of the metastases from tumours of unknown origin were oestrogen receptor positive. It is likely that prolonged fixation in formalin destroys the receptor protein. Immunocytochemical assessment of oestrogen receptor may be the only alternative when dealing with small breast tumours (< 1 cm), in cases of suspected recurrences and in cases of unknown receptor status.
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PMID:[Analysis of estrogen receptors in mammary carcinomas. Is immunocytochemical determination after formalin fixation sufficient?]. 847 71

The study of several human breast cancer cell lines containing oestrogen receptors has allowed characterization of a number of oestrogen-induced proteins (e.g. progesterone receptor, cathepsin D, pS2, Hsp27, c-Myc). In primary tumours these markers have different prognostic significance for predicting whether the tumour will be hormone responsive (e.g. pS2, progesterone receptor) and whether it will metastasize (e.g. cathepsin D). The mechanism of regulation of gene expression by oestrogens and anti-oestrogens in breast cancer is complex and varies according to the nature of both the gene and the cell in which it is transcribed. Our laboratory has identified the sequences mediating oestrogen activity in the proximal region of cathepsin D, including a non-consensus oestrogen-responsive element located at -260 which acts in synergy with other regulatory elements. In addition to the classical effect of oestrogen receptor in stimulating transcription of genes controlled by the oestrogen-responsive element, we found that estrogen receptor is able to modulate transcription of AP-1-responsive genes without interacting directly with DNA. Cross-talk between oestrogen receptor and members of the Fos/Jun family via protein-protein interactions may explain how anti-oestrogens inhibit the mitogenic effect of growth factors in the apparent absence of oestrogens and why tamoxifen is able to stimulate cathepsin D gene expression and induce apoptosis in certain oestrogen receptor-positive breast cancer cells. The nature and degree of this cross-talk appears to vary according to the gene, the cell type and the type of oestrogen receptor ligand involved. Studies of oestrogen-regulated genes are not only useful for classifying breast cancers according to their ability to metastasize and respond to therapies, but also should lead to new therapeutic approaches for hormone-dependent and hormone-resistant cancers.
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PMID:Oestrogen- and anti-oestrogen-regulated genes in human breast cancer. 858 2


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