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 prognostic value of oestrogen receptor (ER) and progesterone receptor (PR) was estimated through a multicentric study of 2257 operable breast cancer patients followed up for a median of 8.5 years. None of the patients had received adjuvant therapy. The series included 33.3% stage I patients, 57.1% stage II, 5.7% stage IIIa and 2.4% stage IIIb. At the end point of the study 589 metastases and 537 deaths from cancer were recorded. Receptor measurements were performed by radiolgand assay according to a uniform protocol. A total of 68.8% of the tumous were ER positive and 54.0% PR positive ( > or = 10 fmol mg-1 cytosol protein). In univariate analysis, ER and PR status (positive/negative) were of prognostic value (P < 0.001) for the disease-free interval (DFI), the metastases-free interval (MFI) and the overall survival (OS). The OS of the patients after a first metastasis was also significantly different between ER-positive and -negative tumours (P < 0.001). In multivariate analysis (Cox proportional hazard model, 1665 patients), only the ER status showed a significant difference (P < 0.01) between positive and negative groups regarding the DFI, MFI and OS. By using Cox non-proportional, time-dependent models, we show that the predictive value of ER status of the primary tumour decreases by approximately 20% per year, losing its significance after 8 years of follow-up. Overall, when compared with TNM and histological grading, ER and PR status have a low prognostic value, their major interest remaining solely in the domain of therapeutic decision.
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PMID:Prognostic value of steroid receptors after long-term follow-up of 2257 operable breast cancers. 919 94

p21 protein (p21) inhibitor of cyclin-dependent kinases is a critical downstream effector in the p53-specific pathway of growth control. p21 can also be induced by p53-independent pathways in relation to terminal differentiation. We investigated p21 immunoreactivity in normal breast and in 91 breast carcinomas [three in situ ductal carcinomas (DCIS) with microinfiltration and 88 infiltrating carcinomas, 17 of which with an associated DCIS; 57 node negative and 34 node positive] with long-term follow-up (median = 58 months). Seven additional breast carcinomas with known p53 gene mutations were investigated. In normal breast p21 expression was seen in the nuclei of rare luminal cells of acinar structures, and in occasional myoepithelial cells. Poorly differentiated DCIS showed high p21 expression, whereas well-differentiated DCIS tumours showed few p21-reactive cells. p21 was seen in 82 (90%) infiltrating tumours; staining was heterogeneous; the percentage of reactive nuclei ranged from 1% to 35%. High p21 expression (more than 10% of reactive cells) was seen in 24 (26%) cases, and was associated with high tumour grade (P = 0.032); no associations were seen with tumour size, metastases, oestrogen receptor status, MIB1 expression and p53 expression. p21 expression in cases with p53 gene mutations was low in six cases and high in one. High p21 expression was associated with short relapse-free survival (P = 0.003).
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PMID:p21WAF1 immunohistochemical expression in breast carcinoma: correlations with clinicopathological data, oestrogen receptor status, MIB1 expression, p53 gene and protein alterations and relapse-free survival. 868 23

A series of 346 patients with primary operable breast cancer and a series of 145 patients with advanced breast cancer were investigated for c-erbB-3 protein expression using the monoclonal antibody RTJ1. Formalin-fixed, paraffin-embedded tumour samples were stained using a standard immunochemical method and staining was assessed on a four-point scale. The study aimed to observe the expression of the c-erbB-3 protein and investigate any relationship between expression and established prognostic indicators and prognosis. In both the primary and advanced series breast tumour tissue was found to stain heterogeneously for c-erbB-3. The staining was observed to be predominantly cytoplasmic and the majority of tumours exhibited moderate positivity. However, 15% and 35% of cases in the primary operable and advanced series respectively displayed strong positive staining. No significant difference was found between the staining in the primary and advanced series. In the primary operable breast cancers, no significant associations were demonstrated with overall survival, disease-free interval, regional recurrence, the presence of distant metastases, age, menopausal status, oestrogen receptor status, histological grade, lymph node stage, vascular invasion and c-erbB-2 protein expression. However, a significant association was seen between the degree of c-erbB-3 immunoreactivity and both tumour size (P < 0.01) and tumour type prognostic group (P = 0.05). No overall association with local recurrence was seen when the four groups of c-erbB-3 expression were analysed (P = 0.12), but when those tumours showing no or weak staining were compared with those showing moderate and strong immunoreactivity it was seen that the latter were significantly more likely to develop local recurrence (P = 0.03). In the series of patients with advanced disease, no significant associations were demonstrated with survival, UICC criteria, age, menopausal status, oestrogen receptor status, histological grade, c-erbB-2 status or the presence of vascular invasion. In conclusion this study found variable expression of c-erbB-3 protein in human breast carcinoma and an association with some recognised prognostic factors in those patients with primary operable breast carcinoma. It seems, however, unlikely that c-erbB-3 protein expression will emerge as a powerful enough prognostic factor to be of value in clinical practice.
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PMID:C-erbB-3 in human breast carcinoma: expression and relation to prognosis and established prognostic indicators. 868 26

Male infiltrating breast carcinomas are rare and seem to have different characteristics, prognosis and sensitivity to hormonal treatment than those of female breast carcinomas. Our aim was to determine whether markers which have an established role in women are also important in men. 66 male infiltrating-ductal breast carcinomas were compared with 190 female breast carcinomas of the same type. Various markers were studied using immunohistochemistry. Tumour size at diagnosis, grade, number of axillary metastases and prognosis were comparable in male and female breast carcinomas. However, male breast carcinomas were characterised by a higher percentage of oestrogen receptor (OR) reactivity, and weekly associated with markers that, in women, are under oestrogen control. Male breast carcinomas were positive for markers under androgen control. Male breast carcinomas also differed from female carcinomas by the low percentage of p53+ and the high percentage of bcl-2+ tumours. The phenotype of male breast carcinomas has characteristics that could have repercussions on prognosis and on the choice of hormonal treatment. Only a few male breast cancers are p53+. OR, which are frequently present in male tumours, are probably not functional. In contrast, androgen receptors seem efficient, as several markers under androgen control are expressed. Therefore, the selection of hormonal therapy should not be based on OR status only.
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PMID:Comparison of prognostic markers detected by immunohistochemistry in male and female breast carcinomas. 898 75

The control of the cell-cycle-associated protein cyclin D1 and its variable behaviour in normal and transformed cells is described and contrasted with its activity in vivo. The role of cyclin D1 as a prognostic and predictive marker is examined in clinical breast cancer. High levels of the protein are seen in well differentiated, oestrogen receptor positive tumours, which respond well to tamoxifen treatment for metastatic disease.
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PMID:Cyclin D1 in mammary carcinoma. 915 10

Although breast carcinomas are considered to originate from glandular epithelial cells, some exhibit 'squamoid features', comprising stratification with a gradient in the nuclear-cytoplasmic ratio within individual cancer cell nests on microscopy. In parallel with a histological review of squamoid features, we immunohistochemically investigated the expression of involucrin, a marker of terminal squamous differentiation, in 223 breast carcinomas with one to three regional nodal metastases but no distant metastases and analysed their association with other clinicopathological parameters to explore their clinical and biological implications. Squamoid features and involucrin expression, detected in 22% and 27% of cases respectively, correlated with each other and were associated with high-grade atypia, a solid-nest pattern, cancer cell necrosis on histology and negative oestrogen receptor status. The incidence of regional recurrences was higher in patients with involucrin expression, whereas bone metastases were less frequent in groups with squamoid features or with diffuse (> or = 10%) involucrin expression. Both squamoid features and involucrin expression, which were considered to be derived either from differentiation into keratinocytes or from some kind of cellular degeneration caused by high turnover rate, are suggested to influence the biological behaviour of breast cancer cells in vivo, and they may be effective in predicting the most likely recurrence sites.
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PMID:Squamoid features and expression of involucrin in primary breast carcinoma associated with high histological grade, tumour cell necrosis and recurrence sites. 916 48

Medroxyprogesterone acetate (MPA) is one of the most commonly prescribed drugs for endocrine therapy of metastatic breast cancer. In this study, the serum MPA concentration was measured by high-performance liquid chromatography (HPLC) and evaluated for its usefulness in predicting the response in 79 cases of advanced or recurrent breast cancers. Overall, 29 patients (37%) achieved an objective response. The response rate correlated significantly with the oestrogen receptor (ER) status (P = 0.03), proliferative activity determined by DNA polymerase alpha (P = 0.04), the disease-free interval (DFI) (P = 0.05) and the serum MPA concentration (P < 0.001). Patients with ER-positive tumours, lower proliferative activity, a longer (DFI) or a higher serum MPA concentration responded more frequently. The mean serum MPA concentration in the responders with ER-positive tumours (P = 0.01) or tumours with a lower proliferative activity (P = 0.008) were significantly lower than in cases with ER-negative tumours or tumours with a higher proliferative activity, respectively. Cases with soft tissue metastases showed responses at significantly lower MPA concentrations (P = 0.003) than those with bone or visceral metastases. Furthermore, there was a dramatic decrease in the MPA concentration when a responder with a high concentration became unresponsive to the therapy. Thus, the serum MPA concentration is a determining factor for the response to treatment.
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PMID:Predictive value of serum medroxyprogesterone acetate concentration for response in advanced or recurrent breast cancer. 933 82

Adenoid cystic carcinoma of the parotid gland often recurs locally, or metastases develop, after initial treatment with surgery and radiotherapy. We report a patient with an inoperable local recurrence of previously irradiated adenoid cystic carcinoma, who was treated with tamoxifen, an oestrogen receptor antagonist. After 18 months of treatment with tamoxifen, MRI showed a partial response, and further clinical progression of the disease was halted.
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PMID:The response of adenoid cystic carcinoma to tamoxifen. 950 15

Liver metastases account for over 70% of deaths resulting from colorectal carcinoma, with survival rates varying between 6-18 months. At present, surgical resection offers the only hope for a cure, while chemotherapy, focal destructive techniques and selective internal radiation offer palliative care. Tamoxifen, a non-steroidal anti-oestrogen is primarily known for treating oestrogen receptor (ER)-positive breast cancer. Some studies suggest that tamoxifen may have beneficial effects in malignancies other than breast cancer. These inhibitory effects, which have been shown to be independent of the ER, highlight new mechanisms of therapeutic action. Using an intrasplenic animal model we report the efficacy of tamoxifen on experimental liver metastases. In this model, a dimethyl hydrazine-induced colon carcinoma cell suspension is introduced into the portal circulation via the spleen, which results in secondary tumour deposits in the liver in virtually all animals. Tamoxifen was administered at a dose of 1 mg/kg suspended in 1.0% methyl cellulose. The control group received an equal volume of the vehicle. The reagents were administered s.c. on the day of metastases induction and were continued daily over a 4 week period. The effect of tamoxifen on tumour growth was assessed by stereology and bromodeoxyuridine immunohistochemistry at selected time points. Data were assessed by a multiple analysis of variance where P < 0.05 was considered significant. In the control group the volume of metastases increased from 44 +/- 41 mm3 at day 10 to 517 +/- 380 mm3, 1394 +/- 598 mm3 and 2082 +/- 675 mm3 by days 16, 22 and 28, respectively. Daily administration of tamoxifen exerted an inhibitory effect on tumour growth during the first 3 weeks, recording a volume of 421 +/- 299 mm3 by day 22 compared with the control group at that time point (P = 0.00004). The inhibitory effect diminished by the fourth week recording a tumour volume of 1344 +/- 674 mm3 by day 28. Inhibition of tumour growth at day 22 coincides with a reduction of cells in the S phase of the cell cycle. The percentage of brdU-positive nuclear profiles in metastases of tamoxifen-treated mice at 3 weeks was 35.87 +/- 5.60% compared with 48.01 +/- 3.96% in the control group (P = 0.001). These data suggest that tamoxifen has a potent inhibitory action on colorectal liver metastases by exerting an effect on cell proliferation.
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PMID:Tamoxifen inhibits colorectal cancer metastases in the liver: a study in a murine model. 964 52

We have investigated factors influencing the survival of women with early breast cancer in Scotland. In a retrospective study, clinical, treatment and 'service' factors, e.g. surgical case load, deprivation and geographical area (health board of first treatment) were recorded from hospital records. A total of 2148 women with invasive breast cancer diagnosed in 1987 were identified from the Scottish Cancer Registry, of whom 1619 without metastases at diagnosis underwent surgery as part of their primary treatment. In a multivariate analysis, clinical factors (age, clinical stage, pathological tumour size, node status and oestrogen receptor status) all influenced survival. After allowing for these clinical factors, surgical case load and deprivation did not have statistically significant effects on survival. By contrast, health board did affect survival. This was explained in part by the selection of patients for surgery. There appeared, however, to be a residual effect that may be related to differences in the use of adjuvant systemic treatment among the different health boards. We conclude that, in Scotland, geographical variation in both surgical and non-surgical treatment has a greater effect on variability in survival for women with breast cancer than surgical case load and deprivation.
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PMID:Variation in the survival of women with breast cancer in Scotland. The Scottish Breast Cancer Focus Group and The Scottish Cancer Therapy Network. 974 92


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