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)

Fulvestrant is a new oestrogen receptor (ER) antagonist that is licensed for the treatment of postmenopausal women with advanced breast cancer progressing following antioestrogen treatment and may also be effective in those progressing after non-steroidal aromatase inhibitors. The use of fulvestrant in a Compassionate Use Programme (CUP) in a "real-life" setting has permitted its activity and tolerability profile in patients with different disease characteristics to be observed. Here, we present five case reports of fulvestrant use in postmenopausal women with advanced breast cancer progressing after prior endocrine therapy. Clinical experience from the CUP supports the published clinical trial data and suggests that fulvestrant is a valuable new treatment for postmenopausal women with advanced breast cancer, including those with visceral metastases and human epidermal growth factor receptor 2-positive disease.
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PMID:Case studies of fulvestrant ("Faslodex") in postmenopausal women with advanced breast cancer. 1619 28

Mutations in the PIK3CA gene have recently been reported in different human neoplasms, including breast cancer. This paper reports the results of a systematic analysis of PIK3CA mutations in different histological types of breast carcinoma. One hundred and eighty invasive breast carcinomas, comprising 74 ductal, 56 lobular, 22 mucinous, 20 medullary, and eight papillary, were selected on the basis of their histological type in a consecutive series of 780 breast cancers. Exons 1-20 of the PIK3CA gene were subjected to SSCP analysis followed by direct sequencing. PIK3CA mutations were observed in 46 (26%) of the 180 tumours examined: 23 (50%) mutations were located in exon 9, and 23 (50%) in exon 20. Mutations were frequent in lobular (46%), less frequent in ductal (22%), and uncommon in medullary (10%), mucinous (5%), and papillary tumours (12%) (p = 0.0002). Mutations in exon 9 were more frequent in lobular carcinomas (30% of cases) than in the other histological types (less than 5% of cases) (p = 0.00014). No significant differences were observed in the distribution of mutations in exon 20. There was no significant correlation between PIK3CA mutations and other clinicopathological and biological variables, including age, tumour size, lymph node metastases, oestrogen receptor (ER) status, progesterone receptor (PgR) status, p53 gene mutations, and p53 protein expression. The findings indicate that in invasive breast carcinomas, PIK3CA alterations are mainly present in lobular and ductal tumours, whereas the other histological types, known to be associated with a favourable prognosis, show a very low incidence of PIK3CA mutations.
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PMID:PIK3CA mutation and histological type in breast carcinoma: high frequency of mutations in lobular carcinoma. 1635 68

ERBB2 (HER2/Neu) gene amplification and overexpression is associated with increased risk of metastases and shorter survival in breast cancer. Tyrosine 1248 is a major phosphorylation site of ERBB2 and reflects the activation status of the receptor. The aim of this study was to investigate the relationships between quantitative levels of pY1248-ERBB2 (p-ERBB2) and the expression of epidermal growth factor receptor (EGFR)-family members, and whether p-ERBB2 could provide additional prognostic value compared with established prognostic markers. For this purpose we developed a highly sensitive chemiluminescence-linked immunoassay (CLISA) and detected p-ERBB2 levels in 70 primary breast cancer biopsies. Phosphorylated ERBB2 correlated with EGFR and ERBB2, and inversely with oestrogen receptor (ER), progesterone receptor (PgR) and ERBB4 expression levels. Additionally, p-ERBB2 was associated with poor clinical outcome in univariate and multivariate Cox regression analysis. Further studies are needed to evaluate the predictive value of p-ERBB2.
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PMID:Phosphorylation of tyrosine 1248-ERBB2 measured by chemiluminescence-linked immunoassay is an independent predictor of poor prognosis in primary breast cancer patients. 1641 59

To evaluate the c-kit expression in breast cancer, 217 invasive ductal carcinomas of the breast were immunohistochemically stained for c-kit protein. The c-kit expression was positive in 59 (27%) of 217 tumours, while the c-kit expression was negative in 158 (73%) of 217 tumours. There was a significant correlation between a negative expression of the c-kit protein and lymph node metastasis (P < 0.0001), and the incidence of a negative expression of the c-kit protein increased as the number of the metastatic lymph nodes increased (P = 0.0003). The c-kit expression did not significantly correlate with the tumour size, nuclear grade, oestrogen receptor status, MIB-1 counts and p53 protein expression. A univariate analysis indicated the patients with the negative c-kit expression to have a worse disease-free survival (DFS) than those with the positive c-kit expression (P = 0.0041), while a multivariate analysis determined lymph node metastases and the MIB-1 counts to be independently significant factors for DFS. In conclusion, a loss of the c-kit expression was found in about three-fourth of invasive ductal carcinoma of the breast and was associated with lymph node metastases. The prognostic implications of the c-kit expression seem to be due to fact that a loss of the c-kit expression is associated with an advanced stage of breast cancer.
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PMID:A loss of c-kit expression is associated with an advanced stage and poor prognosis in breast cancer. 1672 62

Breast cancer is a major source of morbidity and mortality in the elderly population and the number of patients will increase by 30% in future decades. Surgery and endocrine therapy could be considered as the standard treatment in elderly breast cancer patients, but anaesthesia for surgery requires a specific approach taking into account physiological and psychological alterations secondary to ageing. In cases with major alterations of performance status, percutaneous radiofrequency ablation (RFA) could be substituted for the surgical treatment. The aim of the current study is to evaluate the efficacy and feasibility of this technique. Five tumours in four consecutive patients (aged 79-82 years) contraindicated for surgery with symptomatic cT1-2N0M0, positive oestrogen receptor status, low grade were treated by percutaneous radiofrequency-lump ablation under local analgesia, using percutaneous ultrasound guidance. Thermal lesions were produced with RF power 30 W, at a frequency of 500 kHz. Ultrasound-guided percutaneous biopsy of the RF treated breast was performed during the follow-up. We report a successful RFA lump ablation experience in the treatment of four tumours (4/5). One local recurrence occurred within 4 months after RFA. The other biopsies taken during the follow up showed all fat necrosis within the oil cyst and no malignant cells. One abscess occurred at 9 months within the treated area. After a mean follow up of 29.4 months, all the patients are still alive without any other signs of recurrence or metastases. Ultrasound-guided percutaneous RFA is safe and feasible in the management of breast cancer in elderly patients. Nevertheless, further large comparative studies are needed in order to validate such a minimally invasive procedure in current practice.
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PMID:Ultrasound-guided percutaneous radiofrequency ablation in elderly breast cancer patients: preliminary institutional experience. 1706 11

Metastatic eyelid tumours are rare and account for less than 2% of all eyelid neoplasms. We report a case of metastatic breast carcinoma to the eyelid in a 60-year-old Chinese lady presenting with a 2-year history of enlarging, painless nodular lower eyelid swelling. The 1 cm diameter lesion was provisionally diagnosed as a sebaceous cyst. However the excision biopsy revealed a mucinous carcinoma expressing oestrogen receptor protein. She had a past history of mastectomy one year previously and histology showed an infiltrating ductal carcinoma (oestrogen receptor status negative) without evidence of axillary lymph node metastasis. She had completed adjuvant radio- and chemotherapy. Further treatment of the current lesion involved a wide excision which did not show any residual malignancy. She had no other evidence of metastasis and was treated with letrozol. We highlight this case to create awareness among clinicians and opthalmologists on the possibility of metastatic disease as a cause of eyelid swelling, especially in patients with a history of cancer. It may also be the first sign of metastatic disease of an internal malignancy. A review of the literature is also presented.
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PMID:Metastatic mucinous carcinoma of the eyelid. 1719 95

The HER receptors are of therapeutic and prognostic significance in breast cancer, and their function is modulated by cytoplasmic tyrosine kinases like PTK6 (brk). We performed a retrospective study on archival breast cancer samples from patients with long follow-up and compared the protein expression between individual HERs and between HERs and the PTK6. Univariate and multivariate analyses were used to study the prognostic value of parameters. Metastases-free survival of patients for longer than 240 months was inversely associated (P< or =0.05) with nodal status, tumour size, and oestrogen receptor status, but was also directly associated with high protein expression levels of HER4 and PTK6 in Kaplan-Meier analysis. In multivariate analysis for metastases-free survival of >240 months, the stepwise selected parameters were tumour size (relative risk 3.1), PTK6 expression (0.4), and number of positive lymph nodes (1.2). Furthermore, we demonstrated a timedependence of the prognostic value attributed to the parameters. The HER receptors (HER2,4), but not PTK6, were independent prognostic markers for metastases-free survival at 60 months, whereas at 240 months PTK6 is the strongest prognostic marker. We demonstrate that PTK6 is a prognostic marker of metastases-free survival in breast cancer, and is independent of the classical morphological and molecular markers of lymph node involvement, tumour size, and HER2 status.
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PMID:PTK (protein tyrosine kinase)-6 and HER2 and 4, but not HER1 and 3 predict long-term survival in breast carcinomas. 1729 91

SummaryMale breast cancers are rare but have been found in higher proportions in Black Africans. Prognostic factors for breast cancers include tumour size, grade and stage, and hormone receptor status. The hormone receptor status is an invaluable guide in the use of adjuvant endocrine therapy, but none of the reports available in the literature from Africa showed any receptor work.This study was conducted to determine the grade, lymph node status and hormone receptor status of male breast cancers in Ghana.Nine archival cases of male breast cancers from the Pathology Department of Korle Bu Teaching Hospital were selected and studied on the basis of the presence of enough material for immunocytochemistry. Haematoxylin and Eosin (H & E) stained slides were reviewed and graded by Bloom and Richardson's criteria. Lymph node status was also assessed and sections were stained for oestrogen and progesterone receptors.Seven of the nine tumours were invasive ductal carcinomas and six of these were grade II, and one was grade III. Four cases had axillary lymph nodes removed at surgery and three were positive for metastases. Six (66%) of the cases were positive for oestrogen receptors with an H score ranging from 20 to 300. Using the criteria of McCarty et al, positivity for oestrogen receptor was reduced to 44%, which is lower than for Caucasians. We believe that this may be explained by the fact that in Ghana male breast cancers are seen a decade earlier. Only two cases were positive for progesterone receptor with an H score of 10 and 75. The two cases positive for progesterone receptors were also positive for oestrogen receptors.It is concluded that hormone receptor study is important in deciding on endocrine and adjuvant chemotherapy in male breast cancers and should be done routinely to help surgeons plan postoperative management of these patients. We recommend further research in this area.
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PMID:Hormone receptor expression in male breast cancers. 1729 35

An immunohistochemical study was performed using tissue microarrays and specific antibodies against matrix metalloproteinases (MMPs) 1, 2, 7, 9, 11, 13, 14, and their tisullar inhibitors (TIMPs) 1, 2, and 3. More than 2600 determinations on cancer specimens from 131 patients with primary ductal invasive tumours of the breast (65 with and 66 without distant metastasis) and controls were performed. Staining results were categorised using a score based on the intensity of the staining and a specific software program calculated the percentage of immunostained cells automatically. We observed a broad variation of the total immunostaining scores and the cell type expressing each protein. There were multiple and significant associations between the expression of the different MMPs and TIMPs evaluated and some parameters indicative of tumour aggressiveness, such as large tumour size, advanced tumour grade, high Nottinham prognostic index, negative oestrogen receptor status, peritumoural inflammation, desmoplastic reaction, and infiltrating tumoural edge. Likewise, the detection of elevated immunohistochemical scores for MMP-9, 11, TIMP-1, and TIMP-2, was significantly associated with a higher rate of distant metastases. The expression of MMP-9 or TIMP-2 by tumour cells, MMP-1, 7, 9, 11, 13, or TIMP-3 by fibroblastic cells, and MMP-7, 9, 11, 13, 14, TIMP-1, or TIMP-2 by mononuclear inflammatory cells, was also significantly associated with a higher rate of distant metastases.
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PMID:Study of matrix metalloproteinases and their inhibitors in breast cancer. 1734 87

Parotid gland metastases from malignant tumors are extremely rare. A 61-year-old woman was diagnosed with an early breast cancer with no expression of oestrogen and progesterone receptors. Five years later the patient presented a tumour in parotid gland. After total parotidectomy, microscopic analysis of the gland demonstrated an invasive duct carcinoma (IDC) with positive expression of oestrogen receptor. The patient was treated with chemotherapy followed by complementary local radiotherapy. Diagnosis of a metastasic tumour in parotid gland poses a challenge. In our case an immunohistochemical study of oestrogen receptor was fundamental to establish a diagnosis.
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PMID:Parotid gland metastasis of a breast cancer. 1746 82


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