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)

There is preliminary evidence that polymorphism of apolipoprotein E (apoE, protein; APOE, gene), one of the key regulatory proteins in cholesterol metabolism, influences the pathobiology of carcinoma of the colon, prostate and breast and also primary tumours of the brain. This study was designed to determine whether APOE polymorphism is related to variation in the rate of tumour cell proliferation and clinical outcome in carcinoma of the breast. One hundred and eleven infiltrating ductal carcinomas, for which follow up data were available, were included in the study. Estrogen and progesterone receptor status (ER, PR) cell proliferation index (MIB- 1) and APOE genotypes were determined from paraffin-embedded tissue by standard methods. Positive correlations were found between grade and tumour size, grade and presence of metastasis, grade and MIB-1 expression, as well as between ER and PR. Survival correlated inversely with tumour size and the presence of positive lymph nodes. Both steroid receptors correlated inversely with MIB- 1 expression. PR positive status also correlated inversely with high histological grade and presence of lymph node metastases. APOE allele frequencies resembled those of the general population. No significant associations were found between possession of either APOE epsilon2 or epsilon4 alleles and the parameters investigated. Although there is evidence to suggest that APOE epsilon4 may predispose to the development of carcinoma of the breast our data do not support the hypothesis that APOE genotype influences the rate of tumour cell proliferation or the clinical course.
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PMID:Apolipoprotein E polymorphism and breast carcinoma: correlation with cell proliferation indices and clinical outcome. 1111 53

We report a 35-year-old woman with locally advanced mucinous carcinoma of the breast with sudden growth acceleration. A pea-sized mass developed into an ulcerated large tumor within 1 month. After the combination of chemotherapy, radiation and hyperthermia, a radical mastectomy was performed, followed by repair of the skin defect by latissimus dorsi and rectus abdominis musculocutaneous flaps. Histological examination revealed a pure mucinous carcinoma with axillary lymph node involvement. Estrogen and progesterone receptors were not detected in the tumor. Twenty-five months after treatment, there is no sign of recurrent disease. Pure mucinous carcinoma generally has a less aggressive growth pattern as defined by tumor size, adherence to the overlying skin/bottom fasciae, estrogen and progesterone receptor positive and primary lymph axillary lymph node metastases. This case showed completely opposite features to all of these typical biological features of pure mucinous carcinomas.
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PMID:Locally advanced mucinous carcinoma of the breast with sudden growth acceleration: a case report. 1194 31

After a brief historical and experimental introduction, the methods of hormone-based therapy of breast cancer are outlined. It is emphasized that these treatments are only palliative, to be used in advanced cases with surgical, radio- or chemotherapy. The methods include ovariectomy, surgical in acute cases, and by radiation after menopause; complete or partial adrenalectomy; hypophysectomy with indwelling Yttrium 90; androgens (Drostanolone); progestagens; or combined estrogen-progestagens. Castration is suggested for the first treatment, then androgens, or androgens only in aged women. Estrogen-progestagen combinations can be tried in older women. Adrenale ctomy is not advised because it is too dangerous, with little benefit. Hypophysectomy sometimes helps when other hormone therapy is exhausted, but not in tumors known to be hormone resistant. Studies show that ovariectomy does not increase survival time, but lengthens the interval before metastases appear, although the evolution is then more rapid. 30-40% of breast cancers are hormone dependent or sensitive. Visceral and pulmonary metastases are less responsive, and liver and brain lesions almost never respond to hormones.
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PMID:[Hormone therapy of breast cancer]. 1233 27

The use of drugs, which inhibit estrogen biosynthesis, is an attractive treatment for postmenopausal women with hormone-dependent breast cancer. Estrogen deprivation is most specifically achieved using inhibitors which block the last stage in the biosynthetic sequence, i.e., the conversion of androgens to estrogens by the aromatase enzyme. Recently, a new generation of aromatase inhibitors has been developed. Among these, letrozole (Femara) appears to be the most potent. When given orally in milligram amounts per day to postmenopausal women, the drug almost totally inhibits peripheral aromatase and causes a marked reduction in circulating estrogens to levels that are often undetectable in conventional assays. Similarly, neoadjuvant studies demonstrate that letrozole substantially inhibits aromatase activity in both malignant and nonmalignant breast tissues, and markedly suppresses endogenous estrogens within the breast cancers. These studies also illustrate anti-estrogenic and anti-proliferative effects of letrozole in estrogen receptor (ER)-rich tumors. Thus, tumor expression of progesterone receptors and the cell-cycle marker Ki67 is significantly and consistently reduced with treatment. Additionally, clear pathological responses as evidenced by decreased cellularity and increased fibrosis are seen in the majority of cases. These results translated into clinical benefit in a series of 24 breast cancers treated neoadjuvantly with letrozole (either 2.5 or 10 mg): tumor volume reductions > 25% were observed in 23 women, and > 50% reductions in 18 patients. Pathological and clinical effects are seen much more consistently than with tamoxifen. Thus, in a multicenter randomized trial of letrozole vs. tamoxifen (PE 024), clinical study outcomes were superior for letrozole in comparison with tamoxifen with regard to overall tumor response and an increase in the proportion of patients treated by breast conserving surgery. Letrozole has also been used in advanced breast cancer, both as second-line hormone treatment following tamoxifen failure, and more recently as first-line therapy. Trials of second-line treatment in which letrozole has been compared with either older aromatase inhibitors or progestins have shown equivalent or superior clinical activity and improved tolerability favoring letrozole. In first-line comparison with tamoxifen in metastatic disease, a phase III trial of over 900 postmenopausal women showed letrozole to be significantly better than tamoxifen in terms of overall tumor response rates, clinical benefit, and time to treatment failure. In summary, letrozole is an exceptionally potent and specific endocrine agent. In patients with ER-rich tumors, high rates of pathological and clinical response have been documented, and large phase III trials against established treatments such as tamoxifen and progestin suggest superior (or at least equivalent) clinical efficacy. Letrozole is a drug of immense potential and in the future is likely to occupy a central role in the management of postmenopausal women with hormone-dependent breast cancer.
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PMID:Anti-tumor effects of letrozole. 1244 45

Aromatase inhibitors are proving to be more effective than tamoxifen for postmenopausal patients with breast cancer. Estrogen concentrations in the breast are similar in both premenopausal and postmenopausal women, and several fold higher than circulating levels in postmenopausal women. In order to investigate the importance of intratumoral aromatase in stimulating the proliferation of the tumor, we used immunocytochemistry to determine the extent of aromatase expression in relationship to the response of the patient to aromatase inhibitor treatment. The relationship between positive staining for aromatase in the primary tumor and response to treatment with an aromatase inhibitor was investigated in a retrospective study of 102 patients with advanced breast cancer. Immunohistochemical staining using a monoclonal antibody against aromatase was performed on paraffin embedded tumor tissue. Response was evaluated using UICC criteria. Nine out of 13 patients with objective response to treatment stained positive and 49 of 89 patients with stable or progressive disease stained positive. No significant relationship between positive staining and objective response to treatment could be found. When patients with 'clinical benefit' (i.e. objective response plus prolonged stable disease of at least 6 months) were considered, also no relationship could be found. Further analysis of subgroups with positive hormone receptors, treatment with newer generation aromatase inhibitors, single metastatic site, non-visceral metastases and previous treatment only with tamoxifen did not show any relationship. Tumor aromatase expression did not correlate with response of patients with advanced breast cancer to aromatase inhibitor treatment. Most patients had relapsed from other treatments before receiving an aromatase inhibitor. It seems likely that many of these patients had tumors that may have progressed to hormone independence at this stage of the disease. Research in patients who have received treatment with aromatase inhibitors in earlier stages of disease (first line and adjuvant treatment) may provide further information on the relationship between tumor aromatase, steroid receptors and response to inhibitor treatment.
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PMID:The relationship between aromatase in primary breast tumors and response to treatment with aromatase inhibitors in advanced disease. 1467 35

Epithelial malignancies expressing mesenchymal markers and their prognostic implications have been studied by various authors. In view of this, we studied fifty cases of breast carcinomas for vimentin expression and correlated the various clinical and histopathological parameters. Eighteen percent (9/50) of all breast carcinomas expressed vimentin. Vimentin positive tumours were predominantly larger in size (mean greatest diameter 5.43 cm), of higher TNM stage, node negative (55.56%), poorly differentiated (66.66%, p=0.0458) with high mitotic rate (>10/hpf, p=0.0000), Estrogen (88.88%) and Progesterone (77.77%) receptor negative thus pointing towards aggressive biological behavior. Interestingly 20% of well differentiated and 9.09% of moderately differentiated tumours also expressed vimentin. One vimentin positive case had pulmonary metastases despite being node negative while another well differentiated vimentin positive tumour showed skeletal muscle infiltration. Hence, we conclude that vimentin expression is an indicator of biologically aggressive tumours.
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PMID:Vimentin expression in breast carcinomas. 1502 48

The prognosis of patients with de novo stage IV breast cancer seems to be similar to that of patients with metastatic disease. Because these patients have not been exposed to prior therapy, the use of high dose chemotherapy (HDCT) may be beneficial. Twenty-four newly diagnosed (median age 42) responding metastatic breast cancer patients underwent HDCT (Stamp V) and stem cell support as their initial treatment. The predominant sites of metastatic disease were bone (12), lung (5), liver (2), lymph nodes (6), marrow (4), and soft-tissue (1). Estrogen/progesterone receptors were positive in 35%, negative in 45%, and unknown in 20%. Before transplantation, 10 patients were in complete remission (CR), 6 were in partial remission (PR), and 8 were inevaluable. Radiotherapy was administered to sites of documented metastatic disease. Tamoxifen was given to patients with receptor positive and unknown tumor status. After a median follow-up of 60 months from diagnosis (range 42 to 96 months), 15 patients have relapsed and 10 died. Mean and median progression free survival from transplant are 53 (SE 6.6, CI 40-66) and 60 (SE 18, CI 25-96) months, respectively. The median survival has not yet been achieved (>6 years). There was no treatment-related mortality. The use of HDCT in patients with chemosensitive, de novo metastatic breast cancer is safe and well tolerated. Overall clinical outcome is good; however, this study cannot determine whether this was due to treatment or selection bias.
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PMID:High-dose chemotherapy and autologous stem cell transplant in women with de novo chemosensitive metastatic breast cancer. 1517 Jan 43

A pilot study was conducted to assess whether plasma levels of transforming growth factor-beta1 (TGF-beta1) might facilitate biological subgrouping of postmenopausal metastatic breast cancer patients, and, accordingly, its applicability in clinical oncology. This study included 29 postmenopausal metastatic breast cancer patients. Plasma TGF-beta1 levels were detected by enzyme-linked immunosorbent assay (ELISA). Estrogen and progesterone receptors were assayed by radioligand binding, in accordance with the recommendation of the EORTC. Concentrations of 17-beta estradiol were determined by using ELISA-microwell method (DIALAB). Overall survival was followed for 24 months for each individual patient. Stratification of the patients by ER/PR status showed that 14 patients with estrogen receptor-negative, progesterone receptor-negative carcinomas displayed a statistically significant increase in plasma TGF-beta1 levels when compared to plasma TGF-beta1 levels of 6 patients with ER-positive, PR-positive carcinomas (P=0.04). In this study, 7 out of 14 patients with negative receptors' status had no plasma TGF-beta1 values overlapping with patients having positive receptors' status. The TGF-beta1 cut-off value was defined as the highest plasma TGF-beta1 level of ER-positive, PR-positive patients: 3.28 ng/ml. This plasma TGF-beta1 cut-off value defined low-risk subgroup of 19 patients (< or = 3.28 ng/ml) and high-risk subgroup of 10 patients (> 3.28 ng/ml) (P=0.047). Plasma TGF-beta1-related survival was independent of the classical prognostic factors of metastatic breast cancer. Accordingly, a clinical significance of elevated plasma TGF-beta1 levels may be suggested.
Clin Exp Metastasis 2004
PMID:Plasma TGF-beta1-related survival of postmenopausal metastatic breast cancer patients. 1578 95

Breast metastases from gastric cancer are extremely rare. A case report of a 37-year-old female with breast inflammatory invasion and ascites is described. Breast biopsy revealed carcinomatous invasion of the lymphatics from adenocarcinoma cells with signet-ring features. Estrogen (ER) and progesterone receptors (PR) and c-erb-B2 were negative. Upper gastrointestinal endoscopy revealed a prepyloric ulcerative mass. Histopathologic examination of the lesion showed infiltration from a high-grade adenocarcinoma, identical with that of the breast. Immunostaining was positive for cytokeratins CK-7 and CK-20 and CEA and negative for ER and PR. Ascitic fluid cytology was positive for adenocarcinoma cells. Mammography was not diagnostic. Abdominal CT scanning revealed large ovarian masses suggestive of metastases (Krukenberg's tumor). A cisplatin-based regimen was given but no objective response was observed. The patient died six months after initial diagnosis. A review of the literature is performed.
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PMID:Gastric signet-ring adenocarcinoma presenting with breast metastasis. 1671 28

Breast cancer is a major health problem in many parts of the world. Its impact in Saudi Arabia will be more obvious when the national data is released from the National Cancer Registry (NCR) in the near future. It is the most common cancer referred to the King Faisal Specialist Hospital and Research Centre (KFSH&RC). This is a retrospective review of all female breast cancer cases treated at KFSH&RC over a 15-year period. Patients were divided into two groups at the time of their referral to KFSH&RC: metastatic and nonmetastatic. We describe the demographic data, cancer-related information and the treatments offered to all patients. Comparisons were made between Saudi and non-Saudi, and the Saudis were examined in relation to their region of referral and observed to see if any changes occurred during the study period. As well, we tried to compare our results with experience elsewhere. A total of 1584 female breast cancer patients were treated at KFSH&RC between 1975 and 1991. Early breast cancer (Stages I, II) represented 36%, while 64% presented with advanced or metastatic disease (Stages III, IV). The majority of patients were premenopausal (64%). For patients with Stages I-III (1005), mastectomy was performed in 85% and lymph node dissection in 93%. Only 30% had no pathologic lymph node involvement and in 49% of the patients, lymph node dissection was adequate (>/= 10 nodes removed). Estrogen and progesterone receptors were known in 30% of the patients. Sixty-two percent and 72% of patients referred from the central region and the northern region had Stages II and III, respectively. For the non-Saudis, we observed more premenopausal patients (76%) and fewer Stage III. At 15 years, the relapse-free survival in Stages I, II and III was 33%, 36% and 18%, and the overall survival was 80%, 64% and 45%, respectively. Breast cancer in this population affects younger patients (premenopausal) and a higher proportion present with metastatic or locally advanced disease. Management strategies should incorporate conservative surgery when appropriate, and adequate lymph node dissection. This should be coupled with increasing public awareness and education and institution of screening programs. Overall survival is clearly linked to the stage of the disease.
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PMID:An overview of breast cancer. 1737 56


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