Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0278488 (metastatic breast cancer)
 7,812 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A multivariate analysis was performed to assess the effect of post-relapse systemic therapy on a series of patients with metastatic breast cancer who at initial presentation had no detectable metastases (Mo), were less than or equal to 70 years of age, presented with unilateral localized disease and no other associated malignancy, and were treated between 1965 and 1984 with successive protocols for primary disease and subsequently developed distant metastasis. All 760 patients analyzed relapsed with at least one metastasis, and were studied retrospectively with no selection criteria according to any specific protocol. All had recorded clinical data on menopause, stage, clinical tumor aggressiveness (PEV), initial chemo or hormonal therapy, and time to relapse, and had ongoing follow up at our Center, with salvage chemotherapy and/or hormonal therapy having been given to some but not all patients. A brief metastasis-free survival (p less than 0.000001), and factors associated with electing pre-relapse chemotherapy (p less than 0.000001) were associated with shortened post-relapse survival, while post-relapse therapy (chemo p less than 0.0001, and hormonal p less than 0.00001, replacing chemotherapy in the model) apparently increased post-relapse survival in the group overall. This result was similar in the inoperable patient group [with inflammatory breast carcinoma an additional risk factor (p less than 0.0005)], as well as the operable group. However, in the operable group, when the pathologic criteria of histologic grade and nodal status were introduced into the analysis, post-relapse therapy was not seen to be an important factor for survival in any subgroup.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Survival effect of systemic therapy on patients developing metastatic breast carcinoma. 232 26

In spite of major advances in early detection and adjuvant therapy, metastatic breast cancer remains a major clinical problem affecting a significant number of patients. Metastatic disease is generally considered incurable and conventional therapy is used mainly with palliative intent. Therefore, the choice of appropriate therapeutic approach requires a reasoned evaluation of the likelihood of benefit from therapy balanced with the impact of therapy on the patient's quality of life. The estimated aggressiveness of the tumour and indicators of response to therapy (e.g. the status of hormonal receptors) are useful parameters to take into account before selecting a given treatment. Endocrine therapy is an important option in the management of stage IV disease, with tamoxifen the most widely used first-line drug in postmenopausal women. For progressing patients, the third generation of aromatase inhibitors (letrozole, anastrazole) are considered good second-line endocrine agents. The LH-RH agonists represent the initial choice in premenopausal patients candidate to receive hormonal therapy, with the use of tamoxifen as a valuable alternative. Combination chemotherapy regimens (e.g. CMF or CAF) are usually used for first-line treatment of patients with aggressive, steroid receptor-negative disease. Recently, several relatively new agents have shown significant activity in metastatic breast cancer. In particular, the taxanes (paclitaxel and docetaxel) are particularly promising as single agents but also in combination with other drugs, especially anthracyclines. Finally, another class of agents, the d mention because they represent an important new treatment modality in the management of metastatic.
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PMID:[Treatment of metastatic breast carcinoma]. 1046 41

Epidermal growth factor receptor was determined in 106 newly diagnosed breast cancer patients, using the biochemical method. The group consisted of 58 patients in stage I-II, and 48 patients in stage III-IV. Although a significant inverse correlation was found between EGF-R status, and ER or PR status, quantitative content of EGF-R did not correlate either with quantitative ER, or PR levels. The ER/PR content was similar in all clinical stages, suggesting their stability during the clinical course of the disease. EGF-R content was significantly higher in stage IV, compared to stage I, while intermediate clinical stages and all substages did not differ according to the EGF-R content. EGF-R was confirmed as a weak prognostic factor within clinical stages. However, in a whole group, the overall survival was significantly better in patients whose tumors EGF-R content was lower than 26 fmol/mg, compared to those with higher ERF-R content. EGF-R content was highly predictive for the response to systemic endocrine treatment, in metastatic breast cancer patients. In locally advanced breast cancer a trend towards higher levels of EGF-R was found in inflammatory breast cancers, compared to non-inflammatory ones. Slightly higher levels were found in responders to local non-endocrine primary treatments (radiotherapy with or without chemotherapy), compared to non-responders, suggesting the possible predictive role of EGF-R for the response to such treatments. Our results emphasized the usefulness of quantitative receptor determination suggesting the relative stability of EGF-R content during the clinical course of breast cancer, its independence from ER, its significant predictive and weak prognostic values, and a possible correlation with the aggressiveness of the disease, and response to non-endocrine treatments.
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PMID:Expression of epidermal growth factor receptor in breast cancer, from early stages to advanced disease. 1060 81

The helix-loop-helix protein Id-1 inhibits the activity of basic helix-loop-helix transcription factors, and is an important regulator of cell growth and tissue-specific differentiation. We have shown (P. Y. Desprez et al., Mol. Cell. Biol., 18: 4577-4588, 1998) that ectopic expression of Id-1 inhibits differentiation and stimulates the proliferation and invasiveness of mouse mammary epithelial cells, and that there is a correlation between the levels of Id-1 protein and the aggressiveness of several human breast cancer cell lines. Here, we show that aggressive and metastatic breast cancer cells express high levels of Id-1 mRNA because of a loss of serum-dependent regulation that is mediated by a 2.2-kb region of the human Id-1 promoter. Three lines of evidence suggest that unregulated Id-1 expression may be an important regulator of the aggressive phenotype of a subset of human breast cancer cells: (a) a constitutively expressed Id-1 cDNA, when introduced into a nonaggressive breast cancer cell line (T47D), conferred a more aggressive phenotype, as measured by growth and invasiveness; (b) Id-1 was an important mediator of the effects of sex steroid hormones on T47D cell proliferation. Estrogen stimulated proliferation and induced Id-1 expression, whereas progesterone inhibited proliferation and repressed Id-1 expression. Progesterone repressed Id-1 expression, at least in part by repressing transcription. Most importantly, an antisense oligonucleotide that reduced Id-1 protein levels reduced the ability of estrogen to stimulate cell proliferation, whereas constitutive Id-1 expression rendered cells refractory to growth inhibition by progesterone; and (c) using a limited number of breast cancer biopsies, we showed that Id-1 was more frequently expressed in infiltrating carcinomas compared with ductal carcinomas in situ. Our results suggest that Id-1 can control the malignant progression of breast cancer cells, particularly that mediated by sex steroid hormones. Moreover, Id-1 has the potential to serve as a marker for aggressive breast tumors.
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PMID:A role for Id-1 in the aggressive phenotype and steroid hormone response of human breast cancer cells. 1072 95

During the last three decades, research focused on cancer treatment has led to the development of many cytotoxic agents. Despite the fact that these efforts have significantly improved the prognosis of certain malignancies such as some lymphomas, leukemias and testicular carcinomas, other tumors such as ovarian, lung and metastatic breast cancer are still associated with a poor prognosis. An innovative approach has recently emerged, thanks to a better understanding of tumor cell biology and many efforts are aimed at finding compounds capable of restoring a more differentiated phenotype to tumor cells, thereby reducing the tumor's aggressiveness and ultimately reverting it to its normal counterpart [1, 2]. Retinoids are the prototype of this new therapeutical approach called "differentiation therapy".
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PMID:Retinoids in breast cancer prevention and treatment. A review of the literature. 1105 98

The product of the HER-2/neu proto-oncogene, HER2, is the second member of the human epidermal growth factor receptor (HER) family of tyrosine kinase receptors and has been suggested to be a ligand orphan receptor. Ligand-dependent heterodimerization between HER2 and another HER family member, HER1, HER3 or HER4, activates the HER2 signaling pathway. The intracellular signaling pathway of HER2 is thought to involve ras-MAPK, MAPK-independent S6 kinase and phospholipase C-gamma signaling pathways. However, the biological consequences of the activation of these pathways are not yet completely known. Amplification of the HER2 gene and overexpression of the HER2 protein induces cell transformation and has been demonstrated in 10% to 40% of human breast cancer. HER2 overexpression has been suggested to associate with tumor aggressiveness, prognosis and responsiveness to hormonal and cytotoxic agents in breast cancer patients. These findings indicate that HER2 is an appropriate target for tumor-specific therapies. A number of approaches have been investigated: (1) a humanized monoclonal antibody against HER2, rhuMAbHER2 (trastuzumab), which is already approved for clinical use in the treatment of patients with metastatic breast cancer; (2) tyrosine kinase inhibitors, such as emodin, which block HER2 phosphorylation and its intracellullar signaling; (3) active immunotherapy, such as vaccination; and (4) heat shock protein (Hsp) 90-associated signal inhibitors, such as radicicol derivatives, which induce degradation of tyrosine kinase receptors, such as HER2.
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PMID:Biological and clinical significance of HER2 overexpression in breast cancer. 1118 Jul 65

The aggressiveness of human epidermal growth factor receptor-2 (HER2)-positive breast cancer and the poor prognosis of women with this disease demand the availability of accurate and reliable tests for HER2 status and the optimization of HER2-targeted therapy. The distinctive clinical pattern of HER2-positive breast cancer underlines the importance of testing for HER2 status and efforts are ongoing to validate the two major methods in use-immunohistochemistry (IHC), which measures cell membrane HER2 expression, and fluorescence in situ hybridization (FISH), which measures gene copy number. Clinical trial results demonstrate that there is an association between strong HER2 overexpression (IHC 3+) and optimal response to therapy with the novel recombinant HER2 antibody Herceptin. High levels of concordance between IHC 3+ and FISH-positive status have been observed, and response to treatment with Herceptin is similar for patients whose breast cancers are IHC 3+ and those who are FISH-positive. Observations to date have led to the formulation of an algorithm for HER2 status determination and Herceptin use which recommends that: (i) the HER2 status of all women with breast cancer be determined at presentation, (ii) all IHC 3+ and FISH-positive patients with metastatic disease should receive Herceptin, (iii) Herceptin should be used early in the course of metastatic breast cancer and preferably first line, and (iv) Herceptin therapy should be continued until disease progression.
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PMID:Maximizing the response to Herceptin therapy through optimal use and patient selection. 1198 22

In breast cancer the membrane expression of HER2 receptor protein encoded by the HER2 proto-oncogene seems to have an ever growing clinical significance. In tissue cultures and animal experiments it was shown that the HER2 gene amplification induces malignant transformation and intensifies the aggressiveness of the tumour cells. Correlating with the so called pheno-and genotypic prognostic markers, the overexpression of HER2 in breast cancer predicts also poor prognosis and indicates enhanced potential for metastatisation. In some of the so called precancerous proliferations and "in situ" carcinomas we demonstrated the enhanced membrane staining of the HER2 receptor protein. In these cases we frequently observed DNA aneuploidy,the presence of p53 mutational protein and CD44v6 glycoprotein. The immunohistochemical studies of HER2 protein in invasive carcinomas have revealed, an interrelationship between the grade of differentiation, histological type, aggressiveness and biological behaviour of the "in situ" and invasive carcinomas. In clinical studies trastuzumab, a humanized monoclonal antibody recognizing extracellular domain of HER2 receptor protein, has proved to be effective in HER2 overexpressing metastatic breast cancer either as monotherapy or in combination with chemotherapeutical agents. The DAKO "HercepTest" is a semiquantitative, standardised method for the determination of HER2 overexpression.
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PMID:[Expression of HER2 in breast cancer] 1205 Jul 66

Two groups of patients were chosen from among 4,025 subjects examined in a breast screening program, one consisting of patients with stage I and the other of patients with stage IV breast cancer, characterized by neoplastic recurrence. In this comparison p53, HER and grading are of no direct help. We investigated receptor status at the time of the first operation and after complete surgical excision of the recurrence. The following variables were determined: oestrogen and progesterone receptor measures (ER, PR) in f.mol/ml, the 4 receptor phenotypes, the oestrogen-progesterone ratio and histological tumour grading in relation to oestrogen receptor positivity or negativity. Surgery consisted in quadrantectomy or total mastectomy, with axillary dissection or complete surgical excision of the recurrence. Adjuvant therapy was administered. The results show a different receptor percentage in recurrence compared to early breast cancer, which though not significant, indicates a reduced presence of ER+ PR+, ER- PR-, and an increase in the ER+PR- phenotype. Recurrence occurs more frequently when the lesion at the first operation is more advanced and if radiotherapy has not been included in the treatment. Histological grading shows a greater number of undifferentiated cells and a reduction in ER+ in recurrence, thus indicating a reduced target for the most widely used hormone treatments. The oestrogen-progesterone ratio is significantly increased (P < 0.01) in recurrence compared to stage I cancers. The cause of recurrence is a neoplastic embolism, often documented histologically. Recurrence does not necessarily mean a poor prognosis, because there is a survival rate after two years of 77% of the cases treated. These results obtained with widely used methods show the aggressiveness of some breast tumours, which can evolve and have a very poor prognosis even with the most complete therapy.
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PMID:The oestrogen-progesterone receptor ratio: an indicator of breast cancer evolution. 1223 50

The HER2/neu gene encodes a 185 kDa transmembrane receptor (HER2) that belongs to the epidermal growth factor receptor family and has intrinsic tyrosine kinase activity. HER2 is overexpressed in 25-30% of breast cancers and is suggested to have a direct role in the pathogenesis and clinical aggressiveness of HER2 overexpressing tumors. A murine monoclonal antibody, 4D5, directed against the extracellular domain of HER2, is a potent inhibitor of growth of human breast cancer cells overexpressing HER2 in vitro and in xenograft models. To facilitate clinical investigation, 4D5 was humanized by inserting the complementary determining regions of 4D5 into the framework of a consensus human IgG1. The resulting recombinant humanized anti-HER2 MAb, trastuzumab, was found to inhibit the growth of human cancer cells and tumor xenografts overexpressing HER2. Data from phase II trials in women with breast cancer whose tumors overexpress HER2 have shown that trastuzumab has a favorable toxicity profile, is active as a single agent and induces long-lasting objective tumor responses. In combination studies, there was no evidence that trastuzumab enhanced the toxicity of cisplatin and the pharmacokinetic parameters of trastuzumab were unaltered by coadministration of cisplatin. Furthermore, clinical response rates were higher than those reported with either agent alone in a similar patient population. Results of a multicenter, phase III clinical trial of chemotherapy (doxorubicin- or paclitaxel-based) plus trastuzumab as compared to chemotherapy alone in patients with advanced breast cancers overexpressing HER2 showed a significant enhancement in the effects of chemotherapy on time to disease progression, response rates and survival with coadministration of trastuzumab, without increases in overall severe adverse events. Myocardial dysfunction syndrome, similar to that observed with anthracyclines, was reported more commonly with chemotherapy plus trastuzumab. Positive results from clinical studies led to the approval of trastuzumab in the U.S in October 1998 for the treatment of metastatic breast cancer in patients with tumors overexpressing HER2. Since then, the MAb has also been marketed in Switzerland and Canada.
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PMID:Trastuzumab, a humanized anti-HER2 monoclonal antibody, for the treatment of breast cancer. 1297 20


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