Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

With the increasing availability of screening mammography, more women are diagnosed as having breast cancers at an early, node-negative stage. The majority of these patients would be cured with total mastectomy or breast conservation treatment. However, about 30% of the patients would have recurrence of disease in distant sites. In recent randomized clinical trials, adjuvant systemic therapy has been shown to reduce the rate of recurrence in these patients. Proper selection of patients for adjuvant therapy is necessary to avoid exposing many patients with low risk of recurrence to treatments for whom the benefit is not justified by the toxicity and the cost. In this article, we review the clinical and pathologic prognostic factors in early stage, node-negative breast cancer patients, including tumor size, nuclear and histologic grades, estrogen and progesterone receptors, menopausal status, proliferative rate, HER-2/neu oncogene amplification, and cathepsin D level. Favorable prognostic factors include tumor size less than or equal to 2 cm, low nuclear and histologic grades, low S-phase fraction, diploid state, low cathepsin-D level, and positive estrogen and progesterone receptor status. The value of HER-2/neu oncogene overexpression is controversial, and further studies are needed to define its role as a prognostic factor in patients with node-negative breast cancer. Based on these prognostic factors, it is possible to identify subsets of patients who have a low risk of recurrence and would not benefit significantly from adjuvant systemic therapy.
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PMID:Prognostic indicators in node-negative early stage breast cancer. 158 Mar

Amplification of c-myc and c-erb beta-2 (HER-2/neu) proto-oncogenes were analyzed in breast cancer tissues obtained from 100 patients without lymph node involvement (N-). An amplification of the c-myc gene was detected in four cases and a c-erb beta-2 (HER-2/neu) amplification in eight cases. The frequency of these abnormalities were compared to classical prognostic parameters as well as to new biological prognostic markers (cellular cycle, cathepsin-D and pS2 protein). Most of altered tumors were associated to some classical poor prognostic factors such as: steroid receptor-negative tumors, poorly differentiated tumors, high histoprognostic grade and tumor cell density. In contrast, no relation was found with new biological parameters. The analyses of these data in relation to clinical evolution will be of interest to evaluate their prognostic value.
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PMID:[Amplification of c-myc and c-erbbeta-2(HER-2/neu) in breast cancer without axillary lymph node metastasis: correlation with other prognostic parameters]. 770 67

Several investigators, the SEER data, and the ECOG/Intergroup study have shown that patients with small tumors (< 0.5 cm) have a recurrence rate of less than 2%, compared to 20-25% for large tumors (> or = 5 cm). Nuclear grade and tumor differentiation are established indicators; however, the interobserver lack of concordance has thwarted their use in clinical trials. The presence of peritumoral lymphatic and blood vessel invasion (PLBI) is associated with a relative risk of recurrence of 4.7. The predictive value of the presence of hormone receptors in tumors is associated with a favorable disease free and overall survival difference of 8-10%; however, this advantage is being eroded by the early appearance of other factors, such as the epidermal growth factor receptor (EGFR), proliferative capacity (S-phase), nuclear grade, and HER-2/neu oncogene. Concordance among the different methods of hormone-receptor assay (immunocytochemical, sucrose gradient, and dextran-coated charcoal) is essential to refine the true value of these factors. DNA flow cytometry measurements of ploidy (DNA content) and S-phase fraction are the most characterized of the prognostic factors. There are conflicting reports regarding the clinical significance of ploidy status, while measurements of S-phase fraction clearly indicate a robust association with disease free and overall survival. Our data continue to show that S-phase, but not ploidy, can predict time to recurrence significantly in untreated patients, even when data are stratified for tumor size. HER-2/neu oncogene is expressed in about 50% of ductal carcinoma in situ and 14% of invasive ductal carcinoma. The presence of this oncogene at high copy number may be a useful independent marker of poor prognosis and may be associated with drug resistance and correlated with tumor recurrence and shorter survival. EGFR could be measured in most breast tumors, and the level of its expression has inversely correlated with estrogen receptor protein expression. The value of EGFR as a predictor of prognosis remains controversial and is still being investigated. Cathepsin-D provides a provocative biologic rationale but is hindered by different and incongruent methods of analysis. The majority of large studies with more than 3-years' follow-up suggests that high cathepsin-D levels may be predictive of greater recurrence and lower survival. Angiogenesis has been implicated as a critical component of the metastatic process. Early studies show that tumor angiogenesis is an independent and highly significant prognostic indicator, and its presence may suggest the selection of "anti-angiogenic therapy."(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Prognostic factors in early breast carcinoma. 800 12

Many antigenic and genetic markers have been proposed for breast cancer, with potential utility in identification, screening, prognosis, detection, or monitoring. Of the available markers, those with the greatest promise in 1993 include the yet-to-be-cloned BrCa1, the p53 tumor suppressor gene, tissue-associated prognostic factors such as HER-2/neu, cathepsin-D, and indicators of angiogenesis, and circulating tumor markers that provide an indication of clinical course, such as CA15-3 and CEA. However, the precise clinical utilities of all of these markers have yet to be determined. It is especially important that the relative independence of the markers in relation to other available markers to determined so as to avoid the unnecessary cost and expense of redundancy. Moreover, it is important that the clinician be aware of the limitations in both sensitivity and specificity of each marker so as not to sensitivity and specificity of each marker so as not to over- or under-interpret the predictive value of any test. With these caveats in mind, judicial application of germ-line, tissue, and soluble tumor markers can improve clinical care of patients at risk for and with breast cancer.
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PMID:Tumor markers for breast cancer. 811 99

The prognostic significance of cathepsin-D expression was evaluated by immunohistochemistry in 638 node-positive breast carcinomas diagnosed between 1980 and 1986. A minimum of 2.5 years of follow-up was available for each patient (maximum: 9.5 years). Cathepsin-D expression was assessed separately both in cancer and in stromal cells using a commercially available polyclonal antibody. While cancer-cell immunostaining was not associated with prognosis, positive staining of stromal elements was related to shorter metastasis-free survival. The difference in distant metastasis-free survival between positive and negative expressors was greatest in the sub-group of patients submitted to adjuvant chemotherapy, with a hazard ratio for occurrence of distant metastasis of 1.76 by multivariate analysis, but was lowest for those receiving hormone therapy. Cathepsin-D expression by stromal cells was related to HER-2/neu oncoprotein expression, HSP-27 expression, poor nuclear grade, aneuploidy, and absence of estrogen and progesterone receptors. No association was found with the number of involved lymph nodes, tumor size, age, histologic grade, S-phase fraction, or vascular invasion. Our study suggests that cathepsin-D expression by stromal cells (and not by cancer cells) affects the prognosis of breast cancer, that stromal cells probably play a key role in local invasion and metastatic dissemination of the tumor, and that the prognostic significance of cathepsin-D expression may vary according to the type of adjuvant therapy.
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PMID:Prognostic significance of cathepsin-D expression in node-positive breast carcinoma: an immunohistochemical study. 839 64

Tumor-associated markers have potential utility in identification, screening, prognosis, detection, or monitoring breast cancer. Of the available markers, those with the greatest promise in 1994 include the yet-to-be-cloned BrCa1, the p53 tumor suppressor gene, tissue-associated prognostic factors such as HER-2/neu, cathepsin-D, and indicators of angiogenesis, and circulating tumor markers that provide an indication of clinical course, such as CA15-3 and CEA. Unfortunately, the precise clinical utilities of all of these markers remain imprecise. It is especially important that the relative independence of the markers in relation to other available markers be determined so as to avoid the unnecessary cost and expense of redundancy. Moreover, it is important that the clinician be aware of the limitations in both sensitivity and specificity of each marker so as not to over- or underinterpret the predictive value of any test. With these caveats in mind, judicial application of germline, tissue, and soluble tumor markers can improve clinical care of patients at risk for and with breast cancer.
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PMID:Tumor markers for breast cancer. Current utilities and future prospects. 870 69

In order to obtain prognostic clinicopathological information, 49 cases of pure ductal carcinoma in situ of the breast (DCIS), were evaluated for the immunohistochemical expression of potential predictor markers including c-erbB-2 oncogene product, p53 protein, oestrogen (ER) and progesterone (PR) receptors, oestrogen-regulated proteins pS2 and cathepsin-D (cath-D), CD44 protein and 67-kDa laminin receptor (MLuC5). Immunohistochemical findings were compared with conventional pathological parameters, clinical findings, and the clinical outcome of the patients. When markers were matched to each other, statistical analyses provided a significant positive correlation between c-erbB-2 overexpression and p53 positivity (P < 0.01) and between ER and PR (P < 0.01), ER, PR and pS2 (P < 0.01), pS2 and MLuC5 (P < 0.05). Significant negative correlations between c-erbB-2 overexpression and ER (P < 0.05), PR (P < 0.01) and pS2 (P < 0.01) positivity was also observed. Data on the relationship between marker status and pathological findings revealed a significant positive trend between c-erbB-2, p53, and increased grade values (P < 0.05) and opposite results with PR receptor expression (P < 0.01). c-erbB-2 overexpression was further significantly associated with comedotype carcinoma (P < 0.05) and distribution of disease in confluent neoplastic ducts (P < 0.01). Although no statistically significant correlation among biological markers expression, clinical findings and outcome was demonstrated, overall this study indicates that tumour cells from a subset of DCIS, which includes comedotype carcinoma, express significantly unfavourable prognostic factors.
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PMID:Immunohistochemical evaluation of multiple biological markers in ductal carcinoma in situ of the breast. 875 45

Tumor biological factors uPA, PAI-1, cathepsin D, S-phase fraction (SPF), MIB1 (Ki-67), p53, and HER-2/neu were assessed in 100 node-negative breast cancer patients. Their prognostic impact on disease-free (DFS) as well as overall survival (OS) was compared to that of traditional factors tumor size, grading, and steroid hormone receptor status. Antigen levels of uPA, its inhibitor PAI-1, and cathepsin D were determined in tumor tissue extracts by immunoenzymatic methods. SPF was determined by flow cytofluorometry, MIB1, p53, and HER-2/neu by immunohistochemistry in adjacent routinely formalin-fixed paraffin sections. Median follow-up in all patients still alive at time of analysis was 76 months. Univariate analysis determined PAI-1 (p = 0.0001), uPA (p = 0.0437), MIB1 (p = 0.0214), and SPF (p = 0.0248) as statistically significant prognostic factors for DFS. In contrast, tumor size, steroid hormone receptor status, grading, p53, HER-2/neu, and cathepsin. D failed to be of prognostic value. In multivariate analysis, including the statistically significant prognostic factors PAI-1, uPA, MIB1, and SPF, only PAI-1 (p = 0.0003, relative risk: 4.7) proved to be of independent statistical significance for DFS. Regarding OS, PAI-1 was the only statistically significant prognostic factor in univariate (p = 0.0001) as well as multivariate analysis (p = 0.0000, relative risk: 7.1). Thus, factors describing the invasive and metastatic capacity of tumor cells (uPA, PAI-1) and factors related to their proliferative activity (SPF, MIB1) provide valuable prognostic information in node-negative breast cancer patients.
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PMID:Prognostic impact of tumor biological factors on survival in node-negative breast cancer. 970 82

C-myc and c-erbB-2 amplification and/or overexpression as well as total cathepsin-D (CD) concentration have been reported to be associated with poor prognosis in breast cancer. The prognostic significance, however, remains somewhat controversial, partly because of discrepancies among the different methodologies used. We determined the amplification and overexpression of c-myc oncogene in 152 breast cancer patients and examined its prognostic value in relation to c-erbB-2 amplification and overexpression, high concentration of CD (> or = 60 pmol mg(-1) protein) and standard clinicopathological prognostic factors of the disease. High CD concentration, as well as c-myc amplification and overexpression, proved to be the best of the new variables examined for prediction of early relapse (ER; before 3 years). After multivariate analysis only CD remained significant, which suggests that the prognostic power of these variables is similar. Using univariate analysis we proved that c-myc amplification and overexpression were highly significant for disease-free survival (DFS) (P = 0.0016 and P = 0.0001 respectively) and overall survival (OS) (P < 0.0001 and P = 0.0095 respectively), although by multivariate analysis c-myc overexpression was statistically significant only for DFS (P = 0.0001) and c-myc amplification only for OS (P = 0.0006). With regard to c-erbB-2, only its overexpression appeared to be significant for DFS and OS, although after multivariate analysis its prognostic power was weaker (P = 0.030 and P = 0.024 respectively). c-myc amplification and overexpression exhibited a tendency for locoregional recurrence (LRR) (P = 0.0024 and P = 0.0075 respectively), however, their prognostic value was lower after multivariate analysis and only CD remained significant.
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PMID:Determination of c-myc amplification and overexpression in breast cancer patients: evaluation of its prognostic value against c-erbB-2, cathepsin-D and clinicopathological characteristics using univariate and multivariate analysis. 1060 37

A panel of markers used to aid in the diagnosis and treatment of breast cancer was examined in the saliva of a cohort of healthy women, women with benign lesions of the breast, and women with diagnosed breast cancer. We found recognized tumor markers c-erbB-2 (erb), cancer antigen 15-3 (CA15-3), and tumor suppressor oncogene protein 53 (p53) in the saliva of all three groups of women. The levels of erb and CA15-3 in the cancer patients evaluated, however, were significantly higher than the salivary levels of healthy control subjects and benign tumor patients. Conversely, pantropic p53 levels were higher in control subjects compared with those women with breast cancer and those with benign tumors. Although cathepsin-D and epidermal growth factor receptor were detected, they did not demonstrate any clear correlation with disease status. The results of the pilot suggest that these markers have potential use in initial detection and/or follow-up screening for the detection of breast cancer in women.
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PMID:A preliminary study of CA15-3, c-erbB-2, epidermal growth factor receptor, cathepsin-D, and p53 in saliva among women with breast carcinoma. 1070 71


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