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Multivariate analysis of DNA ploidy, p53, c-erbB-2 proteins, EGFR, and steroid hormone receptors for prediction of poor short term prognosis in breast cancer.

BACKGROUND: Several molecular-genetic alterations in breast cancer, including aneuploidy, aberrant expression of p53, c-erbB-2 and EGFR, have been associated with poor prognosis in breast cancer patients particularly those who are lymph node negative. To determine the importance of molecular-genetic factors relative to more traditional surgical-pathologic prognostic factors, multivariate analysis was performed on lymph node positive breast cancer cases. METHODS: One hundred fresh samples of primary breast carcinoma were studied with flow cytometry for DNA ploidy. On the same specimens steroid hormone receptors (ER and PR) were measured in the cytosol fraction using Abbott ELIZA assays, c-erbB-2 and EGFR were determined in the membrane fraction and mutant p53 protein in the nuclear fraction by Oncogene Science ELISA procedures. In addition, information regarding surgical-pathologic features of the tumor was obtained. Multivariate analysis using Cox's proportional hazards model was done to identify variables predictive of poor prognosis. RESULTS: Using univariate analysis, tumor size, lymph node number, p53, c-erbB-2 were predictive of poor short term prognosis. By multivariate analysis, only c-erbB-2 (P = 0.001) and p53 (P = 0.05) were significant. Subsgroup analysis by nodal status yields a significant association of c-erbB-2 (P = 0.001) and p53 (P = 0.04) with lymph node positive breast cancer. CONCLUSIONS: Among molecular-genetic prognostic factors, c-erbB-2 was the most strongly predictive of poor short term prognosis followed by p53 in lymph node positive breast cancer.

Adult↗

[Prognosis and prognostic factor after extended lymphadenectomy in lung cancer].

From 1984 to 1994, 418 patients were received surgery for the lung cancer in our center. Of them, 178 patients were underwent extended lymphadenectomy. Fifty six of the 178 were histologically proven N2 of N3 alpha disease after surgery. Extended lymphadenectomy means R2b lymphadenectomy including the left tracheobronchial node dissection for the right lung cancer and R3 (bilateral mediastinal lymphadenectomy through a median sternotomy) for the left. In the 56 patients, we examined the location and frequency of metastases to the mediastinal lymph nodes and the relationship between some clinical factors (pT, number of metastatic station, clinical staging of the lymph node (CN), histological type, contralateral mediastinal lymph nodes metastases) and prognosis. Most of the pN2 patients of the right lung cancer showed ipsilateral mediastinal lymph nodes metastases and 25 percent of the patients showed the spread to N2b mediastinal modes. The patients of the left lung cancer showed higher incidence of contralateral mediastinal lymph nodes metastases than the patients of the right lung cancer. The five years survival rate of all pN2 patients (N = 39) was 48%, and T1 or T2-N2 patients (N = 22) was 67%. On the other hand, all T4 N2 patients (N-9) died within 3 years after operation. There was no significant difference in postoperative survival between the patients with single station metastasis (N = 20) and multistation metastases (N = 30, including 11 cases with N3 alpha). The five years survival rate of all the patients with multistation metastases was 45%, and that of T1 or T2 multilevel (N = 20) was 65%. There was significant difference in postoperative survival between the patients with CN0-pN2 and CN2-pN2 (p < 0.05). The five years survival of CN0-pN2 patients (N = 14) was 85% and four years survival rate of CN2 pN2 patients (N = 19) was 30%. Among the patients with T1 or T2 tumor, however, there was no significant differences in postoperative survival between CN0-pN2 patients and CN2 pN2 patients. There was no difference in postoperative survival between adenocarcinoma and squamous cell carcinoma (5 years survival: 56%, 43%). In conclusion, extended lymphadenectomy has brought a good prognosis in the patient with T1 or T2 in spite of presence of CN2 or multistation N2. The patients with contralated mediastinal metastases (N3 alpha) showed good prognosis after R3 (5 years survival: 100%) in the patients with the left lung cancer (N = 6). But the N3 alpha patients of right lung cancer showed poorer prognosis (3 years survival: 30%) after R3 (N = 5) than the left. It suggested that R3 lymphadenectomy was significant and beneficial for the left lung cancer patients with N3 alpha but controversial for the right.

Aged↗

Anti-BP180 autoantibodies as a marker of poor prognosis in bullous pemphigoid: a cohort analysis of 94 elderly patients.

The prognosis of bullous pemphigoid (BP), a disorder which usually affects elderly patients, is not well established and conflicting data have been reported about the mortality rate of the disease. Our objective in this study was to assess the clinical and immunological factors determining survival in a prospective series of 94 patients with BP. A cohort of 94 consecutive patients with BP (mean age +/- SD: 81 +/- 4 years) was studied over an 8-year period (1987-94) in one department and patients followed up for at least 1 year. The diagnosis of BP was made on clinical criteria (using a standardized questionnaire), direct immunofluorescence (IF) findings (i.e. linear deposits of IgG and/or C3 along the basement membrane zone) and confirmed by direct immunoelectron microscopy and/or Western immunoblotting. Our analysis (median duration of follow-up: 5 years) showed that 37% of BP patients were dead within a year of starting treatment. The clinical or immunological factors which may influence the prognosis of BP were studied according to the criterion of death or survival by the end of the first year of treatment. None of the following factors was found to be significantly linked to the prognosis in BP: age, sex, extent of skin lesions at presentation, presence of mucosal lesions, blood eosinophilia, or the presence of circulating basement membrane zone autoantibodies by indirect IF. An impaired general condition and a history of coronary artery disease indicated a bad prognosis. The presence of circulating autoantibodies against BP180 autoantigen but not autoantibodies against BP230, as detected by immunoblotting on epidermal extracts, was found to be significantly more frequent (60% vs. 25%) in BP patients who died within the first year of treatment (P < 0.01). We conclude that the presence of circulating autoantibodies against BP180 represents the first intrinsic prognostic factor that has been demonstrated in BP. This result supports the growing body of evidence for the pathophysiological importance of the anti-BP180 autoantibodies.

Aged↗

Immunohistochemical expression of p53 and c-erbB-2 in breast carcinoma: relation with epidemiologic factors, histologic features and prognosis.

We have performed immunohistochemical staining for p53 and c-erbB-2 on formaldehyde-fixed, paraffin-embedded primary invasive ductal carcinomas from 112 patients, with a minimal follow-up time of 60 months. All of them had received postoperative chemoradiation therapy. We have analyzed the association of these factors with epidemiologic risk factors, histopathologic features and hormonal receptor status and the influence on prognosis. Our results indicate that the expression of c-erbB-2 protein defines a group of node-negative patients with poor prognosis. The overexpression of c-erbB-2 has shown a significant association with estrogen receptor status (those tumors expressing c-erbB-2 are usually estrogen receptor negative), presence of fibrosis and lymphoplasmacytoid infiltrates. P53 expression has shown no relation either with prognosis or with any other histopathologic or clinical feature. The only factors with prognostic influence in our series have been tumor size, the presence of node metastases, TNM stage and the prognostic morphometric index (Baak's index), apart from c-erbB-2 in node-negative patients. However, only the TNM stage showed an independent association with prognosis after a multivariate analysis. In summary, in our experience the expression of p53 protein has no prognostic influence on breast carcinoma, and TNM stage remains to be as the most powerful prognostic factor in these patients.

Adult↗

Prediction of nodal metastasis and prognosis in breast cancer: a neural model.

BACKGROUND: An increasing number of women with breast cancer are detected with the disease at an early stage, when the lymph nodes are not involved. In order to obviate the necessity to carry out axillary dissection, accurate surrogates for lymph node involvement need to be identified. In this paper we have examined the use of a neural network to predict nodal involvement. The neural approach has also been extended to investigate its predictive applicability to the long-term prognosis of patients with breast cancer. A number of established and experimental prognostic markers have been studied in an attempt to accurately predict patient outcome 72 months after first examination. METHODS: 81, unselected patients, presenting clinically, who had all undergone mastectomy for invasive breast carcinoma were considered in this study. A total of 12 markers were analysed for the prediction of lymph node metastasis, while node status itself was used as an additional marker for the prognostic analysis. In this case the outcome related to whether a patient had relapsed within 72 months of diagnosis. In both cases, a number of marker combinations were analysed separately in an attempt to classify those most favourable marker interactions with respect to lymph node prediction and prognosis. Patients were randomly divided into a training set (n = 50) and a test set (n = 31). The simulation was developed using the NeuralWorks Professional II/Plus software (NeuralWare, Pittsburgh, Pa, USA). RESULTS: In the case of lymph node metastasis, the neural network was able to correctly predict axillary involvement, or otherwise, in 84% of the patients in the test set by considering 9 of the 12 available markers. This represents an improvement of 10% over the traditional approach which considers the tumour grade and size only. The sensitivity and specificity were also shown to be 73% and 90%, respectively. With regard to patient prognosis, again 84% classification accuracy was obtained using a subset of the markers, with a sensitivity of 50% and a specificity of 96%. CONCLUSIONS: Although this study considered a relatively small sample of patients, nevertheless it demonstrates that artificial neural networks are capable of providing strong indicators for predicting lymph node involvement. There is no longer a need for axillary dissection with all its implications in patient morbidity and demands on clinical resources. The management of breast cancer and the planning of strategies for adjuvant treatments is also facilitated by the use of neural networks for the long-term prognosis of patients.

Biomarkers, Tumor↗

Value of right ventricular ejection fraction in predicting short-term prognosis of patients with severe chronic heart failure.

BACKGROUND: The prognosis of chronic heart failure has been studied extensively, but factors predicting short-term outcome in patients with severe chronic heart failure are still poorly defined, and the current indications for heart transplantation as a treatment for end-stage heart failure need on objective analysis. METHODS: Purpose of the study was to identify the determinants of short-term prognosis in a group of 142 consecutive ambulatory patients (mean age 49.8 +/- 11 years). Referred for heart transplantation because of severe chronic heart failure, the patients were admitted with left ventricular ejection fraction markedly depressed and had had symptoms in spite of an optimal standardized medical therapy for at least 1 month. Baseline clinical and instrumental evaluation included right-sided heart catheterization with a flow-directed multilumen thermodilution catheter, which enables determination of pressures, cardiac output, right ventricular volumes, and ejection fraction. RESULTS: Most patients were in New York Heart Association class III (61%) and IV (24%), and the hemodynamic profile was characterized by mean left ventricular ejection fraction of 20.2% +/- 6%, cardiac index of 2.13 +/- 0.6 l/min/m2, pulmonary capillary wedge pressure of 23.1 +/- 11 mm Hg, right atrial pressure of 7.9 +/- 6 mm Hg, right ventricular ejection fraction of 23.2% +/- 12.4%. During a mean follow-up of 11.1 +/- 9.4 months, 33 patients underwent transplantation (23.4%), 41 died (28.8%), and 68 were still alive (47.8%). There was a substantial overlap in left ventricular ejection fraction between patients divided on the basis of outcome, whereas right ventricular ejection fraction was significantly lower in patients who died or underwent transplantation. Cox multivariate analysis showed three independent prognostic variables: cause (p = 0.03), heart failure score (p = 0.001), and right ventricular ejection fraction (p = 0.000). Short-term survival (10 months) was significantly (p = 0.000) different in patients with > or = 24% or < 24% right ventricular ejection fraction. Statistical analysis identified right ventricular ejection fraction as the single variable to be highly correlated with an increased risk of early death. CONCLUSIONS: This study suggests that right ventricular function is a crucial determinant of short-term prognosis in severe chronic heart failure. Statistical analysis identified right ventricular ejection fraction, determined by thermodilution during right-sided heart catheterization, as the single most important predictor of short-term prognosis in a large cohort of patients who had symptoms in spite of a standardized, optimized, multipharmacologic treatment. The variable allows a useful risk stratification in patients with severe chronic heart failure and uniformly depressed left ventricular ejection fraction and provides guidance in the assessment of indications and timing for transplantation.

Adolescent↗

Multivariate analysis of DNA ploidy, p53, c-erbB-2 proteins, EGFR, and steroid hormone receptors for short-term prognosis in breast cancer.

BACKGROUND: Several molecular-genetic alterations in breast cancer, including aneuploidy, aberrant expression of p53, c-erbB-2, and EGFR have been associated with poor prognosis in breast cancer particularly in lymph node negative patients. To determine the importance of molecular-genetic factors relative to more traditional surgical-pathologic prognostic factors, a multivariate analysis was performed particularly in lymph node positive breast cancer cases. METHODS: One hundred fresh samples of primary breast carcinoma have been studied with flow cytometry for DNA ploidy. On the same specimens steroid hormone receptors (ER and PR) were measured in cytosol fraction using Abbott ELIZA assays, c-erbB-2 and EGFR were determined in the tissue homogenate and mutant p53 protein in the nuclear fraction by Oncogene Science ELISA procedures. In addition, information regarding surgical-pathologic features of the tumor was obtained. Multivariate analysis using Cox's proportional hazards model was done to identify variables predictive of poor prognosis. RESULTS: With univariate analysis, tumor size, lymphnode number, p53, c-erbB-2 were predictive of poor short term prognosis. In the multivariate analysis, only c-erbB-2 (P = 0.001) and p53 (P = 0.05) were significant. Subgroup analysis by nodal status yielded significant association of c-erbB-2 (P = 0.001) and p53 (P = 0.04) with lymph node positive breast cancer. CONCLUSIONS: Among molecular-genetic prognostic factors, c-erbB-2 was the most strongly predictive of poor short term prognosis followed by p53 in lymph node positive breast cancer.

Adult↗

[Clinical aspects of Behçet's disease--epidemiological features and visual prognosis].

Behçet's disease patients who visited the eye clinic of Tokyo University Hospital during the past 20 years were surveyed retrospectively, and their epidemiological features and visual prognosis were demonstrated. We evaluated the number of patients, sex ratio, age of onset, ratio of complete type to incomplete type, and ratio of major symptoms other than the ocular manifestation. The results showed a tendency similar to the results of the nationwide hospital survey in Japan. We also evaluated the visual prognosis of Behçet's disease patients in our clinic by the least square method. In the groups of patients whose visual acuity at the initial visit was over 0.4, the visual prognosis of those who visited from 1984 till 1993 was significantly better than that of those who visited from 1974 till 1983. The use of cyclosporine was presumed to be one of the most important factors in the improved visual prognosis of Behçet's disease patients in our clinic.

Adolescent↗

Breast cancer: poor short-term prognosis in cases with moderate lymphocyte infiltration at the tumour edge: a preliminary report.

Lymphocyte infiltration in breast carcinoma has long been associated with favourable prognosis, however it has also been related to poor prognosis. In this study of 128 consecutive cases lymphocyte infiltration, its absence, or presence and degree was recorded at the tumour edge adjacent to fatty tissue in 100 cases, to other tissues in the remaining 28 in which no such edge was found. In the former there was a highly significant prognostic difference between those with moderate infiltration, which was of poor short-term prognosis, and those with other degrees of infiltration (none, slight and marked). Thus, lymphocyte infiltration in breast cancer can give information on both good and poor prognosis in over 80% of cases if its site and degree are taken into consideration. The remaining cases are histologically distinct. Their survival was similar to that in the total material. The mechanisms involved are as yet open to speculation. In view of increasing surgical reluctance to remove the axillary nodes it is of interest that the present investigation can be carried out on the routine diagnostic specimen from the primary and that the relation between survival and axillary nodal status, significant in the total material, no longer held in these groups.

Adenocarcinoma↗

[Neurologic prognosis after cardiocirculatory arrest outside the hospital].

OBJECTIVE: To detect clinical signs and times of evaluation able to identify patients with good neurologic prognosis after out-of-hospital cardiac arrest. EXPERIMENTAL DESIGN: Retrospective study with 6 months-2 years of follow-up. SETTING: General intensive care unit, from 1993 to 1995. PATIENTS: Twenty-three patients aged 18-80 years, admitted with coma after out-of-hospital cardiac arrest, who survived at least 24 hours, without concomitant neurologic disorders. INTERVENTIONS: Neurologic outcome classification in three categories: complete neurologic recovery (A), moderate to severe disability (B), death without regained consciousness (C); A and B groups of patients are considered together as a "good neurologic outcome" group. MEASUREMENTS: Evaluation of some neurological parameters (GCS, motor response to pain, spontaneous motility, cranial nerve reflexes, spontaneous breathing, seizures) 6 hours (t0), 24 hours (t1), 72 hours (t2) and 7 days (t3) after arrest. RESULTS: Patients with good prognosis are identified with 100% sensitivity from the following parameters: at t0 none; at t1 motor response to pain, GCS > 4, absence of seizures; at t2 the former parameters, spontaneous breathing, brain stem reflexes, normal pupils; at t3 all the former parameters and spontaneous motility. Specificity is greater than 50% only for motor response to pain and GCS > 4. CONCLUSIONS: It is mostly impossible to state a neurologic prognosis in the first hours after cardiac arrest. The single predictor with the most reliable prognostic value is motor response to pain which allows, if present, to identify all the patients with a good prognosis as early as 24 hours after arrest.

Adolescent↗

The prognosis of biopsy-proven lupus nephritis in chinese patients: long term follow-up of 86 cases.

OBJECTIVE: To investigate the prognosis of lupus nephritis (LN) and its influencing factors in patients with lupus nephritis in China. METHODS: A retrospective study was carried out in 86 patients followed up for at least 5 years. Clinical features, serological and immunological tests were investigated. Renal biopsies were performed at the beginning of the study and repeated in some cases during the follow-up period. All the 86 patients had serum creatinine (Scr) level less than 132.6 mumol/L at the initial presentation and were divided into three groups according to the level of Scr at the end of the study. Group I: the patients with normal renal function (Scr < 132.6 mumol/L); Group II: the patients with mild-moderate renal insufficiency (132.6 mumol/L < or = SCR < or = 530.4 mumol/L); Group III: the patients with end stage renal failure (ESRF) (Scr > or = 530.4 mumol/L). RESULTS: Forty-seven patients reached clinical remission with normal renal function, 11 had with stabilization of renal function, although the systemic lupus erythematosis (SLE) activity relapsed repeatedly, while 28 subjects developed renal insufficiency after 60-170 (mean 88.12 +/- 28.23) months of observation. ESRF rate was 11.6% in this group of patients. Eight patients died (2 died of infections and 6 died of ESRF) during the follow-up period. At the beginning of the study the rates of hypertension, persistent anemia and hematuria in Group II were 50%, 70%, and 70% respectively, being much higher than those in Group I. The calculation of AI and CI in 60 patients revealed that there were 65% of patients with AI > or = 7 and 70% of patients with CI > or = 3 in Groups II and III, while in Group I there were only 32% of patients with AI > or = 7 and 19% of patients with CI > or = 3. Sixteen cases had pathologic class changed in 48 repeated biopsies. Seven cases changed to Class IV, 5 to Class II, 3 to Class V from other classes and one to class III from Class II. CONCLUSIONS: Factors associated with the development of renal insufficiency in these lupus patients included hypertension, anemia and hematuria. Renal biopsy evaluation offered additional prognostic information and showed that patients with severe active and chronic histologic changes were at risk for developing renal insufficiency. During the clinical course, the renal classification of LN changed in certain patients, thus the histologic classification of renal morphology at initial presentation did not fully predict the outcome. Renal involvement is very common in systemic lupus erythematosis (SLE) patients. Lupus nephritis (LN) is the most common form of secondary renal disease in China. It has various and unpredictable clinical features. The risks associated with its treatment have challenged investigators to detect the factors which may influence the survival rate of patients with LN and to develop the rational approaches to therapy. Decades of intensive investigation at many centers around the world had underscored the predictive value of demographic, clinical and laboratory data prior to treatment. Controversies still existed due to the difference in environment, race and the selection criteria of patients as well as the method used to evaluate the outcome. There are still some factors which are thought to have an impact on the prognosis of LN. Most of the articles on the prognosis of patients with LN were reported from Europe and America either about Caucasian or African-American patients. The prognosis of LN and its influence in Chinese patients need more elucidation.

Adult↗

[Natural history and prognosis in infective endocarditis].

The natural history and prognosis of native valve infective endocarditis, prosthetic endocarditis and right sided endocarditis in drug addicts is analyzed. In native endocarditis mortality during the active phase is 12% and survival at 10 years 81%. Early prosthetic endocarditis has a worse prognosis. In late prosthetic valve endocarditis prognosis depends on the infective organism: mortality is less than 10% in estreptococcal infections and higher than 50% in staphylococcal infections. Right sided endocarditis in intravenous drug addicts has a relatively benign prognosis and seldom requires surgical treatment.

Endocarditis, Bacterial↗

Cyclin DI amplification is not associated with reduced overall survival in primary breast cancer but may predict early relapse in patients with features of good prognosis.

Amplification of chromosome 11q13 is frequently observed in human malignancies, including breast cancers. A candidate oncogene at this locus is the CCND1 gene, which encodes the cell cycle regulatory protein cyclin D1. Because published data on the relationship between 11q13 amplification and prognosis in breast cancer have been controversial, we investigated the clinical significance of CCND1 amplification and its association with established clinicopathological features of prognosis in 1014 primary breast cancer patients. Amplification of the CCND1 gene and the INT-2/FGF-3 gene, which also maps to 11q13, was 10% and 17%, respectively. There were no associations between CCND1 or INT-2 amplification and patient age, tumor size, tumor grade, axillary lymph node status, HER/neu amplification, MIB-1 monoclonal antibody to Ki67 antigen count, or p53 expression. CCND1 amplification was predominantly observed in hormone receptor-positive tumors; at a copy number >/=3, CCND1 amplification was significantly correlated with both estrogen receptor (ER; P = 0.036) and progesterone receptor (P = 0.012) positivity. After a median follow-up period of 66 months, CCND1 or INT-2 amplification was not associated with significant increases in relapse or death from breast cancer. However, in the node-negative and ER-positive subgroups, there was a trend for an increased relapse rate in patients with INT-2 or CCND1 amplification. Thus, in this study, assessment of CCND1 or INT-2 amplification at 11q13 by slot-blot hybridization was of little use in determining phenotype or disease outcome in the whole group of patients but had a potential role in identifying a subset of poor-prognosis patients within the node-negative or ER-positive, good-prognosis groups. Because the prevalence of CCND1 amplification is much lower than the reported prevalence of cyclin D1 overexpression, additional studies are required to determine the true prognostic significance of altered cyclin D1 expression in breast cancer.

Adult↗

p53 codon 72 polymorphism in Taiwanese lung cancer patients: association with lung cancer susceptibility and prognosis.

An association between the BstUI (Pro/Pro) genotype of the p53 codon 72 polymorphism and lung cancer has been reported previously (X. Jin et al., Carcinogenesis (Lond.), 16: 2205-2208, 1995). However, the genotype distribution of p53 codon 72 polymorphism as well as the association of this polymorphism with lung cancer risk and prognosis remain undefined in the Taiwanese population. Therefore, we investigated the genotype distribution of p53 codon 72 polymorphism in 194 lung cancer patients and 152 noncancer controls. The genotype frequencies in Taiwanese noncancer controls were 0.56 (Arg) and 0.44 (Pro). Chi2 analysis indicated significant differences in genotype distribution of p53 from other reports in Swedish (P < 0.001), Spanish (P < 0.001), Caucasians in the United States (P = 0.002), and African-Americans (P = 0.027). In addition, our data suggest that the Pro allele of the p53 codon 72 polymorphism increased the risk of lung cancer among female Taiwanese. The female patients with genotype Pro/Pro showed a significantly increased odds ratio (3.14; confidence interval, 1.48-6.64; P = 0.003) of having lung adenocarcinoma, compared with normal controls with the other genotypes. Patients with the Pro/Pro genotype had an odds ratio of 2.63 (confidence interval, 1.22-5.68; P = 0.01) higher than those with the other genotypes to be diagnosed with lung cancer at the early ages. We further investigated the association of p53 codon 72 polymorphism with prognosis in 133 lung cancer patients. Patients with the Pro/Pro genotype tended to have poorer prognosis than those with the Arg/Pro genotype (P = 0.05, by the log-rank test). Our data suggested that p53 codon 72 polymorphism may play a role in cancer susceptibility and prognosis in specific classes of lung cancer patients in Taiwan.

Adenocarcinoma↗

High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with early poor prognosis breast cancer.

BACKGROUND: Overall survival rates are disappointing for women with early poor prognosis breast cancer. There is a hypothesis that high dose chemotherapy with autologous bone marrow or stem cell transplant (autograft) may improve survival rates by permitting higher doses of adjuvant chemotherapy to be given. OBJECTIVES: To compare the effectiveness of high dose chemotherapy and autograft versus conventional chemotherapy for women with early poor prognosis breast cancer. SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group specialised register, The Cochrane Controlled Trials Register (Cochrane Library Issue 3, 2002), MEDLINE (1966 to Aug. 2002), EMBASE (1980 to Aug. 2002), PsycINFO (1984 to Aug. 2002), Cinahl (1982 to July 2002), the websites of co-operative research groups and ASCO (American Society of Clinical Oncologists) and reference lists of articles found. SELECTION CRITERIA: Randomised controlled trials comparing the effectiveness of high dose chemotherapy and autograft versus conventional chemotherapy for women with early poor prognosis breast cancer. DATA COLLECTION AND ANALYSIS: We identified nine trials that met the inclusion criteria. Three independent reviewers extracted data. MAIN RESULTS: In total 1758 women were randomised to receive high dose chemotherapy with autograft and 1767 women were randomised to receive conventional chemotherapy. There were 48 non cancer-related deaths on the high dose arm and four on the conventional dose arm (RR 7.74, 95% CI (3.43, 17.50). Since many studies have not completed follow-up, overall survival rates were in most cases based on results to date. There was no statistically significant difference in overall survival between women who received high dose chemotherapy with autograft and women who received conventional chemotherapy, either at three years (RR 1.02, 95% CI (0.98, 1.06)), or at five years (RR 0.98, 95% CI (0.93, 1.05)). There was a statistically significant benefit in event-free survival at three years for the group who received high dose chemotherapy (RR 1.11, 95% CI (1.05, 1.18)). However at five years there was no statistically significant difference between the groups (RR 1.00, 95% CI (0.92, 1.08)). Side-effects were more common and more severe in the high dose group though most were reversible. Women in the high dose group reported significantly worse quality of life scores immediately after treatment but at one year there was no statistically significant difference between the groups in quality of life scores. REVIEWER'S CONCLUSIONS: There is insufficient evidence to support the routine use of high dose chemotherapy with autograft for women with early poor prognosis breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

High dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with early poor prognosis breast cancer.

BACKGROUND: Overall survival rates are disappointing for women with early poor prognosis breast cancer. Autologous transplantation of bone marrow or peripheral stem cells (in which the patient is both donor and recipient) has been considered a promising technique because it allows much higher doses of chemotherapy to be used. OBJECTIVES: To compare the effectiveness of high dose chemotherapy and autograft versus conventional chemotherapy for women with early poor prognosis breast cancer. Outcomes were survival rates, toxicity and quality of life. SEARCH STRATEGY: We searched the Cochrane Breast Cancer Group specialised register, The Cochrane Controlled Trials Register (Cochrane Library Issue 3, 2004), MEDLINE (1966 to November 2004), EMBASE (1980 to November 2004), PsycINFO (1984 to November 2004), Cinahl (1982 to November 2004), web sites of co-operative research groups and ASCO (American Society of Clinical Oncologists) and reference lists of articles found. SELECTION CRITERIA: Randomised controlled trials comparing high dose chemotherapy and autograft versus conventional chemotherapy for women with early poor prognosis breast cancer. DATA COLLECTION AND ANALYSIS: Fifteen trials were considered. Thirteen were included and two were excluded. Three independent reviewers extracted data. MAIN RESULTS: Analysis included 2535 women randomised to receive high dose chemotherapy with autograft and 2529 randomised to receive conventional chemotherapy. There were 65 treatment-related deaths on the high dose arm and four on the conventional dose arm (RR 8.58 (95% CI 4.13, 17.80). Many studies have not completed follow-up and have reported only preliminary results. There was a statistically significant benefit in event-free survival for women in the high dose group at three years (RR 1.12 (95% CI 1.06, 1.19)) and at four years (RR 1.30 (95% CI 1.16, 1.45)). At five and six years there was no statistically significant difference between the groups in event-free survival. With respect to overall survival, there was no statistically significant difference between the groups at any stage of follow up. Morbidity was more common and more severe in the high dose group. However there was no statistically significant difference between the groups with respect to the incidence of second cancers at five to seven years' follow up. Women in the high dose group reported significantly worse quality of life scores immediately after treatment, but few statistically significant differences were found between the groups by one year. AUTHORS' CONCLUSIONS: There is insufficient evidence to support the routine use of high dose chemotherapy with autograft for women with early poor prognosis breast cancer.

Antineoplastic Combined Chemotherapy Protocols↗

The needs of terminally ill cancer patients versus those of caregivers for information regarding prognosis and end-of-life issues.

BACKGROUND: The difficulty of negotiating the concerns of family members while also respecting the needs of the patient adds complexity to the task of discussing prognosis and end-of-life (EOL) issues with terminally ill cancer patients. The informational needs of caregivers may be different from those of the patients themselves with regard to these topics. However, to the authors' knowledge, this issue has received relatively little research attention. METHODS: The authors conducted focus groups and individual interviews with 19 patients with far advanced cancer and 24 caregivers from 3 palliative care (PC) services in Sydney and 22 PC health professionals (HPs) from around Australia. The focus groups and individual interviews were audiotaped and fully transcribed. Additional focus groups or individual interviews were conducted until no additional topics were raised. The participants' narratives were analyzed using qualitative methodology. RESULTS: The participants had varying views regarding whether patients and caregivers should be told different information concerning prognosis and EOL issues. Three themes were identified from the transcripts regarding meeting the informational needs of both the patients and caregivers: 1) the importance of consistency and openness, 2) the specific information needed to care for the patient, and 3) the value of having separate discussions with the patient and caregiver. A desire to restrict the patient's access to information by the caregiver or vice versa was reported by the HPs to be one of the most challenging issues when discussing prognosis and EOL issues. Three themes were identified with regard to this issue: 1) autonomy versus protection, 2) negotiating family dynamics, and 3) difficulty using interpreters. CONCLUSIONS: The results of the current study emphasized the importance of considering the distinct informational needs of caregivers, as well as those of the patient, when discussing prognosis and EOL issues.

Adult↗

Prognosis of functional capacity and work capacity in rheumatoid arthritis.

In the study functional capacity and work capacity were investigated in a series of 405 hospital patients suffering from rheumatoid arthritis. One-third of the patients had had the disease for 5 years, one-third for 10 years and one-third for 15 years. The functional capacity index presented by Lee et al. (1973) was used. Half of the patients in the 5 and 10-year groups and one-third of those in the 15-year group had good functional capacity. One-fourth in the 5 and 10-year groups and one-third of those in the 15-year group had poor functional capacity. Sixty per cent of the 5-year group, 50 per cent of the 10-year group and 33 per cent of the 15-year group were able to work. The prognosis of functional capacity and work capacity was better for young persons than for older ones. No differences were found between the prognoses for men and women. High ESR, a positive blood rheumatoid factor and joint erosion seemed to be linked with an unfavourable prognosis of functional capacity. Light work was favoured for the prognosis of functional capacity and work capacity and extensive general education and vocational training for work capacity. The results indicate that starting vocational rehabilitation at an early stage of the disease could improve the prognosis of functional capacity and work capacity.

Adolescent↗