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)

Expression of c-erbB3 protein was investigated in 104 primary breast carcinomas comprising nine comedo ductal carcinoma in situ (DCIS), 91 invasive ductal carcinomas and four invasive lobular carcinomas using two monoclonal antibodies, RTJ1 and RTJ2. Of the 91 invasive ductal carcinomas, seven contained the comedo DCIS component adjacent to the invasive component. An immunohistochemical technique was used to evaluate the association between expression of c-erbB3 and clinical parameters and tumour markers such as epidermal growth factor receptor (EGFR), c-erbB2, cathepsin-D and p53 in archival formalin-fixed paraffin-embedded tumour tissues. Our results indicated that RTJ1 and RTJ2 gave identical staining patterns and concordant results. It was found that the overexpression of c-erbB3 protein was observed in 67% (6/9) of comedo DCIS, 52% (44/84) of invasive ductal carcinomas, 71% (5/7) of carcinomas containing both the in situ and invasive lesions and 25% (1/4) of invasive lobular carcinomas. A significant relationship (P < 0.05) was observed between strong immunoreactivity of c-erbB3 protein and histological grade, EGFR and cathepsin-D, but not with expression of c-erbB2, p53, oestrogen receptor status, lymph node metastases or age of patient. However, we noted that a high percentage of oestrogen receptor-negative tumours (59%), lymph node-positive tumours (63%) and c-erbB2 (63%) were strongly positive for c-erbB3 protein. We have also documented that a high percentage of EGFR (67%), c-erbB2 (67%), p53 (75%) and cathepsin-D-positive DCIS (60%) were strongly positive for c-erbB3. These observations suggest that overexpression of c-erbB3 protein could play an important role in tumour progression from non-invasive to invasive and, also, that it may have the potential to be used as a marker for poor prognosis of breast cancer.
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PMID:Expression of c-erbB3 protein in primary breast carcinomas. 982 84

This paper outlines the changes which have occurred over the last 25 years in the methods employed for the measurement of oestrogen receptors to aid the management of women with breast cancer. Immunohistochemistry is now the method of choice and knowledge of oestrogen receptor status is being used with increasing frequency for the selection of adjuvant treatment as well as for the treatment of metastatic disease. It is essential that good quality assurance procedures are established so that results are reproducible and can be used with confidence in individual centres as well as being comparable with those produced elsewhere. A retrospective study of 170 women with metastatic breast cancer provides the basis for a discussion on the advantages and pitfalls of the immunohistochemical assay. Particular emphasis is paid to the choice of cut-off and how the results may be applied in patient management.
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PMID:Increased use of immunohistochemistry for oestrogen receptor measurement in mammary carcinoma: the need for quality assurance. 989 51

Genetic alterations of tumour suppressor genes, for which loss of heterozygosity (LOH) is one mechanism of gene inactivation, are important steps in the development of endometrial cancer. To investigate the clinical relevance of LOH of BRCA1 (17q21), TP53 (17p13) and TCRD (14q11) in endometrial cancer, polymerase chain reaction (PCR)-based fluorescent DNA technology for the detection of microsatellite polymorphisms was applied. One hundred and thirteen archival endometrial cancer samples with matched normal tissues were examined. Allele loss at three loci were correlated with age, tumour size, lymph node status, metastases, stage, histological types, grade, expression of oestrogen receptor (ER) and progesterone receptor (PgR), family history of cancer, previous history of cancer or precursor lesions, and previous history of hormone replacement therapy (HRT). LOH for BRCA1 was detected in 18.1%, of TP53 in 26.9%, and of TCRD in 26.3% of informative cases. LOH of BRCA1 correlated with medium grade, positive ER status, and family history of cancer; LOH of TP53 correlated with younger age, high grade, positive PgR status, and with tumours from patients without HRT; LOH of TCRD correlated only with family history of cancer. LOH at all three loci correlated only with grade and positive family history. Allele loss of one of the three tumour suppressor loci did not correlate with disease-free survival (DFS), but LOH of BRCA1 correlated significantly with decreased overall survival (OS). The latter, together with the correlation of LOH of BRCA1 locus with steroid hormone receptor expression, might give a hint to the potential involvement of the co-localised 17 beta-hydroxysteroid dehydrogenase (HSD) gene in the development of endometrial cancer.
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PMID:Loss of heterozygosity of BRCA1, TP53 and TCRD markers analysed in sporadic endometrial cancer. 989 67

We have shown previously that the relative expression of a truncated oestrogen receptor-alpha variant mRNA (ER clone 4) is significantly increased in axillary node-positive primary breast tumours compared with node-negative tumours. In this study, we have examined the relative expression of clone 4-truncated, exon 5-deleted and exon 7-deleted oestrogen receptor-alpha variant mRNAs in 15 primary breast tumour samples and in synchronous axillary lymph node metastases. Overall, there were no significant differences between the primary tumours and the matched metastases in the relative expression of these three specific variant mRNAs. Furthermore, the pattern of all deleted oestrogen receptor-alpha variant mRNAs appeared conserved between any primary and its matched secondary tumour.
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PMID:Oestrogen receptor-alpha variant mRNA expression in primary human breast tumours and matched lymph node metastases. 1007 Sep

Bone metastases can present to a number of different specialties and their successful management requires a coordinated approach with good liaison between the specialists. Patients who respond to systemic therapy for their metastases have a good chance of being alive at 3 years, and 20% will be alive at 5 years. This means that it is worth palliating these patients properly. With this in mind, the intention of this document is to try and improve the process of care for women with metastatic bone disease from breast cancer. These guidelines consider all aspects of care from diagnosis to assessment of response to treatment, and describe the Quality Objectives that should be addressed at each stage. The level of available evidence is indicated throughout the document where possible. In considering diagnosis, the guidelines emphasize the value of having a dedicated orthopaedic surgeon specifically linked to each Cancer Unit. The attachment of a dedicated orthopaedic surgeon will ensure that mechanical problems are correctly identified, and that actual or imminent fracture is correctly managed. The latter is particularly important as the management of pathological fractures is not the same as that of traumatic fractures. The orthopaedic surgeon should also act as the liaison between his/her own Unit and the tertiary spinal or neurosurgical centres as necessary. In addition, empowering the radiologist means that the diagnostic process can be accelerated and refined. The place of different investigations in diagnosis, including tumour markers, is discussed. The guidelines emphasize the need for a definitive diagnosis before treatment in the (rare) case of a solitary metastasis. The treatment section discusses orthopaedic management, radiotherapy and systemic treatments (endocrine therapy, chemotherapy and bisphosphonates). The guidelines emphasize the emergency nature of spinal cord compression, describing the need for fast access to assessment and for good liaison between specialists. It is essential that these are available and widely publicized to ensure effective management. The role of radiotherapy in both local pain relief and spinal cord compression is discussed, and various techniques are described. Endocrine therapy and chemotherapy are discussed in relation to the disease-free interval, performance status, extent and site of metastatic disease, and oestrogen receptor status. Specific chemotherapy regimes are not discussed as these are subject to change and local protocols should be followed. The increasing evidence behind the role of bisphosphonates is reviewed. With many unanswered questions about the long-term use of this group of drugs, the guidelines offer a scoring system for deciding which patients might benefit most from long-term bisphosphonate therapy. The guidelines describe the possible ways of assessing response to treatment and the difficulties that may be encountered, including a discussion of the role of tumour markers in assessment of response. A final section looks at palliative care principles in bone pain management, acknowledging the need for continuation of good care throughout the patient's journey, from diagnosis onwards. We very much hope these guidelines will stimulate individuals and institutions to improve the process of delivering care to this group of patients.
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PMID:British Association of Surgical Oncology Guidelines. The management of metastatic bone disease in the United Kingdom. The Breast Specialty Group of the British Association of Surgical Oncology. 1018 49

The prolactin-inducible protein (PIP/GCPD15) is believed to originate from a limited set of tissues, including breast and salivary glands, and has been applied as a clinical marker for the diagnosis of metastatic tumours of unknown origin. We have investigated the potential role of PIP mRNA as a marker of human breast cancer metastasis. Using reverse transcription polymerase chain reaction and Southern or dot blot analysis, PIP mRNA was detected in 4/6 breast cell lines, independent of oestrogen receptor (ER) status. In breast primary tumours (n = 97), analysed from histologically characterized sections, PIP mRNA was detected in most cases. Higher PIP mRNA levels correlated with ER+ (P = 0.0004), progesterone receptor positive (PR+) (P = 0.0167), low-grade (P = 0.0195) tumours, and also PIP protein levels assessed by immunohistochemistry (n = 19, P = 0.0319). PIP mRNA expression was also detectable in 11/16 (69%) of axillary node metastases. PIP mRNA expression, however, was also detected in normal breast duct epithelium, skin, salivary gland and peripheral blood leucocyte samples from normal individuals. We conclude that PIP mRNA is frequently expressed in both primary human breast tumours and nodal metastases. However, the presence of PIP expression in skin creates a potential source of contamination in venepuncture samples that should be considered in its application as a marker for breast tumour micrometastases.
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PMID:The potential role for prolactin-inducible protein (PIP) as a marker of human breast cancer micrometastasis. 1057 57

Infiltrating ductal mammary carcinomas are histologically graded according to their extent of differentiation. Well-differentiated, grade I, tumours have low proliferative activity, usually form tubules and exhibit little nuclear pleomorphism. Despite an apparently reassuring morphology, 10-15% of grade I ductal carcinomas metastasize, albeit after a prolonged period. Recent evidence supports the view that evolution to higher grade malignancies occurs rarely and that grade I tumours are biologically distinct from grade III tumours. We have examined a series of 148 grade I ductal carcinomas in order to ascertain whether information about the level of expression of cyclin D1, p27, p53, oestrogen receptor status (ER) or proliferative activity could be used to identify those patients with a poor outcome. The majority of tumours expressed high levels of cyclin D1, p27 and ER, low levels of p53 and had low Ki-67 expression and mitotic counts. Cyclin D1, p27 and ER expression were all significantly correlated with each other but not with p53 (cyclin D1 correlation with ER, p = 0.01; cyclin D1 correlation with p27 and ER correlation with p27 both p < 0.0001). Cyclin D1 and ER were also both correlated with Ki-67 (p = 0.01 and p < 0.0001) but not with mitotic count. Our results suggest that cyclin D1, ER and p27 are all markers of well-differentiated tumours and that their detection is related to proliferative activity in a manner reflecting their functional role within the normal cell cycle. However, none of the proteins or markers of proliferative activity were sensitive enough to predict which patients were likely to have a poor outcome.
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PMID:Cell cycle proteins do not predict outcome in grade I infiltrating ductal carcinoma of the breast. 1071 27

Over 30% of breast cancers are diagnosed after age 70. The incidence of breast cancer in the elderly has increased since 1960. Risk factors for breast cancer are a medical history without pregnancy, a first pregnancy after age 30 and the use of hormonal replacement therapy. The biology of breast cancer at advanced age indicates a relative slow, less aggressive and hormone dependent tumour growth. In spite of these favourable characteristics, the prognosis is not better than at middle age. Over 20% of older patients die from co-existing other diseases within 5 years after the diagnosis of breast cancer. This comorbidity, mostly cardiovascular or pulmonary, affects the possibilities and the outcome of treatment. Treatment of the primary tumour is performed according to the same guidelines as in younger patients. Indication exists for hormonal adjuvant treatment with tamoxifen in patients with oestrogen receptor positive tumours. Hormonal treatment is the treatment of choice in metastatic disease. Chemotherapy is given in patients with oestrogen receptor negative tumours and in patients with progressive hepatic or pulmonary metastases.
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PMID:[Breast cancer in patients, 70 years or older]. 1087 4

The purpose of the present paper was to evaluate the characteristics and outcomes of male breast cancer patients seen for adjuvant therapy at a single institution. A retrospective review of computerized records in the Departments of Medical and Radiation Oncology at the Royal Prince Alfred Hospital (RPAH) was undertaken. Between 1983 and 1996, 24 men were referred for treatment of breast cancer. Of these, 19 had localized breast cancer, four had metastatic disease and one had ductal carcinoma in situ (DCIS). The median age was 57.5 years (range: 26-78) and median follow-up was 6.2 years (range: 0.6-36). Pathological staging was performed. Survival was assessed using actuarial life table analysis. Of the 19 patients who presented with localized disease, there were 12 T1, five T2 and two T4 cancers. Eleven patients had axillary lymph node involvement. Ten patients were oestrogen receptor (ER) positive, two patients were ER negative and seven patients had unknown receptor status. All patients underwent surgery. Eleven patients received radiotherapy. The median dose and dose per fraction were 50 Gy and 2 Gy, respectively. Adjuvant systemic therapy was delivered to 10 patients, of whom nine were node-positive. Four patients received chemotherapy alone, three patients received chemotherapy and tamoxifen, and three patients received tamoxifen only. Seven patients relapsed (one local, five distant, one both). Of the two patients with local relapses, one had received radiotherapy. Of the distant failures, four of six patients had no systemic therapy. There were only two node-positive patients who were not given systemic treatment and both relapsed. Median survival in all patients with invasive cancer was 7.5 years, and in those with localized disease it was 7.6 years. The median survival of node-positive patients was 3.8 years. In node-negative patients the median survival had not been reached at a median follow-up of 6.2 years. The majority of patients (12/14) with known receptor status were ER+, a finding that parallels those of other studies. Local control rates were 88% (7/8) in patients who had mastectomy alone and 91% (10/11) in those patients receiving adjuvant radiotherapy. Systemic therapy was found to be beneficial in patients with node-positive disease. Chemotherapy was administered more frequently than hormonal therapy. The median survivals were consistent with those reported in other series.
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PMID:Carcinoma of the male breast: a review of adjuvant therapy. 1090 73

Some experimental studies suggested that one possible oestrogen-receptor-unrelated mechanism of action of tamoxifen involves inhibition of angiogenesis. We evaluated the correlation of the degree of vascularisation of the primary tumour and we assessed it by using the panendothelial marker anti-CD31 and immunohistochemistry with microvessels count, performed at the vascular 'hot spot' of each single cancer, with the risk of recurrence in time. A cohort of 176 consecutive patients with node-positive invasive breast cancer treated with adjuvant tamoxifen (30 mg/daily for 3 years) and a median follow-up of 72 months was studied. Sixty-two patients developed metastasis (30 visceral, 18 skeletal and 14 in soft tissues) during the time of observation. The study of the hazard function for metastasis was performed by a generalized linear modelling approach with a binomial error according to Efron. The risk of first recurrence was strictly associated with vascular index, having the patients with the highest microvessel counts the highest risk of metastasis during all the period of observation. We did not find an interaction of vascularity with oestrogen receptor (ER) status. However, in the subgroup of patients with ER-positive tumours the hazard of metastasis was almost constant in time, while in that with ER-negative tumours it increased rapidly up to 20 months and, thereafter, decreased sharply. The results of our study are an indirect evidence that the patients with highly vascularized breast cancers may gain poor benefit of adjuvant tamoxifen and, therefore. that this antioestrogen is unlikely to retain a clinically relevant antiangiogenic activity in human breast cancer. Our data need confirmation by a prospective randomized clinical trial.
Clin Exp Metastasis 2000
PMID:Behaviour of metastasis in relation to vascular index in patients with node-positive breast cancer treated with adjuvant tamoxifen. 1120 33


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