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The influence of CYP2D6 genotype on the efficacy of tamoxifen (Tam) has been extensively analyzed in early breast cancer with conflicting results. However, there is only scarce data regarding this potential influence in advanced breast cancer (ABC). We hypothesize that Tam is more effective in patients with a functional CYP2D6 allele than in patients with impaired CYP2D6 activity. ABC patients with prior or ongoing palliative Tam treatment (20 mg/d) were eligible. Genomic DNA was extracted from blood (n = 51) and formalin-fixed, paraffin-embedded tissue (n = 43). CYP2D6*2, *3, *4, *5, *6, *10, *17, *29, *41, CYP2D6 duplication and multiplication were determined in blood and CYP2D6*4 in tissue samples. Primary endpoint was progression free survival (PFS); secondary endpoints included clinical benefit (CB), and overall survival (OS). The clinical charts were retrospectively analyzed regarding survival and treatment effects. Genotyping was performed blinded and clinical data were analyzed separately. 94 patients were identified with a median age of 59 years (29-90 years). In 6 patients genotyping did not show conclusive results, therefore these patients were excluded from further analysis. Genotyping results were as follows: 1.1 % ultrarapid, 84.1 % extensive, 3.4 % intermediate, and 11.4 % poor metabolizers. Patients without any fully functional allele (IM/IM, IM/PM, PM/PM) had a significant shorter PFS and OS compared to patients with at least one functional allele (EM/EM, EM/IM, EM/PM) (PFS: p = 0.017; HR = 2.19; 95 % CI 1.15-4.18; OS: p = 0.028; HR = 2.79; 95 % CI 1.12-6.99). The CB rate was 73 % for EM-group and 38.5 % for IM + PM-group (p = 0.019). Our results show a significant influence of the CYP2D6 genotype on the efficacy of Tam in the treatment of ABC. In contrast to the adjuvant setting, the evidence in the palliative setting is congruent. CYP2D6 testing in ABC should be considered.

Background: Coronary computed tomography angiography (CCTA) provides information regarding lesion morphology and three-dimensional coronary anatomy incremental to coronary angiography. We addressed the question whether preprocedural CCTA bears potential for guiding percutaneous coronary interventions (PCI)., Methods and Results: Sixty-six coronary lesions attempted with PCI within 6 months of preprocedural CCTA were retrospectively assessed. Lesion parameters from unenhanced computed tomography (CT) for calcium scoring and CCTA were analyzed and compared with PCI complexity. Complex PCI was defined as use of buddy wire, kissing balloon, necessity of high pressure balloons, or rotablator. Complex PCIs were observed in 32 interventions (48%). Median Agatston score and Hounsfield units were higher in lesions with complex as compared to those with non-complex interventions with 130 (interquartile range, 23-276) vs 29 (0-158; P=.01), and 493 (245-631) vs 341 (68-520 Hounsfield Units; P=.04), respectively. Median local plaque volume and plaque mass were higher in complex PCI with 17 (2-39) vs 5 (0-19.5 mm³; P=.007), and 48 (15-99) vs. 16 (1.5-63 mg hydroxyapatite/mm³; P=.03), respectively. Lesions leading to complex PCI were longer [1.8 (1.2-2.8) vs 1.3 (0.8-1.7) cm; P=.03], and had a higher rate of calcified plaques (23% vs 3%; P=.03). There was a significant correlation between CCTA- and angiography-derived local SYNTAX Scores (P<.001); the CCTA-derived score seems to be predictive for failed and complex PCI (area under curve = 0.75 ± 0.13 and 0.66 ± 0.08, respectively)., Conclusions: Preprocedural lesion assessment by CCTA indicates complexity of PCI. In patients with suspected complex coronary anatomy, prior CCTA adds important information for planning PCI.

Unlabelled: This retrospective multi-centre study is focussed on recurrence free and overall survival of bilateral breast cancer (BBC) versus unilateral breast cancer (UBC). The impact of BBC on survival is stratified to guideline adherence, according to the German national S3-guideline. Another aim of the study is to identify the influence of various guideline violations in adjuvant treatment on survival of BBC patients. 229 (4.3%) patients had BBC and 5063 (95.7%) had UBC. There is a significant association between BBC/UBC and recurrence free (RFS: p < 0.001) and overall survival (OAS: p = 0.003). Only 15.7% of patients with BBC are treated 100% guideline adherent (index- + contralateral tumour). 31.0% (30.5%) were guideline adherent with respect to the index (contralateral) tumour. The outcome decreases significantly with the number of guideline violations. There was no significant difference in RFS and OAS between BBC and UBC after adjusting for tumour size, nodal status, grading and if guideline adherent treatment was applied., Conclusion: 1. Patients with BBC have primarily a worse prognosis in terms of RFS and OAS than patients with primarily UBC. 2. There is a strong association between guideline adherence and RFS/OAS of patients with BBC or UBC. The outcome decreases with the number of guideline violations. 3. If guideline adherent treatment was applied (for both tumours in case of BBC) there was no significant difference in RFS and OAS between BBC and UBC after adjusting for tumour size, nodal status, grading., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Aim of the Study: Clinical practice guidelines (CPG) are an appropriate method to optimise routine clinical care. Numerous CPGs for the diagnosis and treatment of breast cancer have been developed by national health institutions or medical societies. While a comparison of methodological criteria has been undertaken before, it is unknown whether these CPGs differ in their actual treatment recommendations., Methods: We included national breast cancer CPGs from the USA, Canada, Australia, the UK, and Germany that satisfy internationally recognised methodological criteria and are in widespread use in daily clinical care. Treatment recommendations for adjuvant invasive breast cancer including surgery, radiation, endocrine therapy, chemotherapy and anti-HER2-therapy were compared., Results: Recommendations for endocrine therapy show discordances regarding optimal usage of ovarian function suppression for premenopausal patients and aromatase inhibitors for postmenopausal patients. However, most other treatment recommendations exhibit a large degree of congruency. This reflects the fact that they rest on the same evidence base, and that many national guidelines are adopted from other guidelines so that well accepted guidelines are cited within other guidelines., Concluding Statement: Considering that the development of guidelines is a very expensive and resource-intensive task the question arises whether the development of national guidelines in numerous countries is worth the effort since the recommendations differ only marginally., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Purpose: The development and implementation of the "Interdisciplinary S3 Guideline for the Diagnosis, Treatment and Follow-up Care of Breast Cancer" (3) is intended to optimise national health services. This guideline already serves both as a basis for the certification of German breast centres and for the external comparative quality assurance based on guideline based quality indicators. Nevertheless, the effects of the implementation on relevant outcomes have not been examined so far., Methods: The retrospective cohort study analyses data of 3,976 female patients with primary breast cancer which were collected at the University of Ulm and co-operating certified breast centres between 2001 and 2005. Based on the S3 guideline, an analysis model was developed to allow for the examination of guideline-adherent therapy on the basis of the guideline recommendations, and the effects of guideline-adherent compared to not guideline-adherent therapy on overall (OAS) and recurrence-free survival (RFS) were examined subsequently., Results: In total, 2,063 (51.9%) of the 3,976 patients were treated in adherence the guideline. In 1,913 (48.1%) patients deviations from the guideline recommendations in at least one of the therapeutic options were found. The variable "guideline-adherent treatment" had significant influence on RFS [p < 0.001; HR=2.20; 95% CI (1.74 to 2.79)] and OAS (p < 0.001; HR=2.57; 95% CI (1.96 to 3.37)], each adjusted for age, tumour size, nodal status and grading. RFS decreases with the number of deviations from guideline recommendations [1 to 2 deviations: p < 0.001; HR=2.04; 95% CI (1.60 to 2.60); ≥ 3 deviations: p < 0.001; HR=3.64; 95% CI (2.43 to 5.45), also adjusted for age, tumour size, nodal status and grading]. Similar results were found for the OAS., Conclusion: Patients with breast cancer should be treated in adherence to guideline recommendations. Deviations and barrier factors will have to be evaluated in the future in order to further optimise both the guideline and guideline-adherent therapy., (Copyright © 2011. Published by Elsevier GmbH.)

Background: The aim of that study was to analyze the impact of German-S3-breast cancer guideline adherence on clinical outcomes., Methods: A retrospective study analyzed 3976 patients first diagnosed with primary breast cancer according to an S3-guideline-based model that classified patients retrospectively into groups receiving "guideline-adherent and "guideline non-adherent" therapy., Results: There was a significant association between treatment adherence and prolonged recurrence free and overall survival (p = 0.0001). The greater the number of violations in guideline adherence, the lower was overall survival (p = 0.0001). Advanced age at initial diagnosis was additionally associated with a reduction in guideline adherence. The percentage of guideline adherence for the therapeutic modalities BCT, mastectomy, axillary dissection and hormone therapy was greater than 80%. For chemotherapy, the percent of guideline adherence totaled 71.4%., Conclusion: Therapies dispensed in adherence with guidelines may improve recurrence-free survival and overall survival in patients with breast cancer., (Copyright 2009 Elsevier Ltd. All rights reserved.)

Background and Objective: Guidelines for the treatment of early-onset breast cancer have been proposed in several countries, but to date, their impact on outcomes is unverified. The objective of this study was to evaluate the association between guideline-adherent versus nonadherent treatment and recurrence-free survival (RFS) and overall survival (OAS) in early-onset breast cancer patients., Methods: A total of 1,778 patients were included in the study, of whom 111 were 35 years or younger and 1,667 were between 36 and 55 years. RFS and OAS were compared between the two groups, with respect to multiple parameters. All survival data were adjusted for tumor characteristics and analyzed with respect to guideline adherence according to the German Step 3 guidelines., Results: Statistically significant differences between the two groups (<35 years, 36-55 years) were observed with regard to breast surgery (p = 0.002) and hormone therapy (p = 0.006). Both groups were treated identically in terms of guideline adherence concerning axillary dissection (p = 0.9), radiation therapy (p = 0.7) and chemotherapy (p = 0.556). Young breast cancer patients whose treatment adhered to guideline recommendations had increased RFS and OAS [RFS: p = 0.030, hazard ratio (HR) 2.95, 95% confidence interval (CI) 1.11-7.83; OAS: p < or = 0.001, HR 2.92, 95% CI 2.01-4.23]., Conclusion: Guideline-adherent treatment for early-onset breast cancer patients significantly improves OAS and RFS and should therefore be demanded for all patients., (Copyright 2010 S. Karger AG, Basel.)

Background: To date, few studies have investigated whether the implementation of national breast cancer guidelines fulfills the goal to optimize the national standard of care. Therefore, we aimed to evaluate retrospectively the guideline-related 13-year data on breast cancer patients treated at our institution., Patients and Methods: In a retrospective cohort study, the records of a total of 2,231 patients with primary breast cancer treated during the period of 1992-2005 at the Department of Obstetrics and Gynecology, University of Ulm, Germany, were analyzed. Based on the German national Step 3 (S3) guideline, a model was created to classify groups according to therapy 'conforming' and 'non-conforming' to guideline recommendations., Results: In 2005, 70.2% of all patients included received both surgical and systemic adjuvant therapies conforming to the guideline. Guideline-conforming treatment was accompanied with significant advantages in terms of recurrence-free survival (RFS) and overall survival (OAS) rates., Conclusions: It has to be demanded that breast cancer patients are treated in conformity with the S3 guidelines. The reasons for a treatment not conforming to the guidelines should be analyzed for the detection of barrier factors, in order to optimize adherence to the guidelines and therefore to prolong RFS and OAS., ((c) 2010 S. Karger AG, Basel.)

Purpose: The role of high-dose chemotherapy (HDCT) in metastatic breast cancer remains controversial. Trials with late intensification HDCT have failed to show an advantage in overall survival. This study was initiated to compare up-front tandem HDCT and standard combination therapy in patients with metastatic breast cancer., Patients and Methods: Patients without prior chemotherapy for metastatic disease were randomly assigned to standard combination therapy with doxorubicin and paclitaxel (AT) or double HDCT with cyclophosphamide, mitoxantrone, and etoposide followed by peripheral-blood stem-cell transplantation. HDCT was repeated after 6 weeks. Patients were stratified by menopausal and hormone-receptor status. The primary objective was to compare complete response (CR) rates., Results: A total of 93 patients were enrolled onto the trial. Intent-to-treat CR rates for patients randomized to HDCT and AT were 12.5% and 11.1%, respectively (P = .84). Objective response rates were 66.7% for patients in the high-dose group and 64.4% for patients in the AT arm (P = .82). In an intent-to-treat analysis, there were no significant differences between the two treatments in median time to progression (HDCT, 11.1 months; AT, 10.6 months; P = .67), duration of response (HDCT, 13.9 months; AT, 14.3 months; P = .98), and overall survival (HDCT, 26.9 months; AT, 23.4 months; P = .60). HDCT was associated with significantly more myelosuppression, infection, diarrhea, stomatitis, and nausea and vomiting, whereas patients treated with AT developed more neurotoxicity., Conclusion: This trial failed to show a benefit for up-front tandem HDCT compared with standard combination therapy. HDCT was associated with more acute adverse effects.

Background: The American College of Cardiology/American Heart Association (ACC/AHA) stenosis morphology classification (MC) stratifies coronary lesions for probability of success and complications after coronary angioplasty (PTCA). Modern computing techniques were used to evaluate the individual predictive value of MC in random PTCA cases., Methods and Results: MC was attributed to the target lesions by consensus of 2 observers. The predictive value regarding procedural success (PS) and major adverse cardiac events (MACE) of MC was analyzed by conventional logistic regression analyses and by inductive machine learning models. The study was adequately powered for the methods applied with 325 target lesions of 250 cases. Overall, PS decreased and MACE increased from type A to type C lesions. Regression analysis identified no single factor as predictive. Logistic regression showed an error rate of 42%. Machine learning techniques achieved an individual predictive error of only 10%, which could be further reduced to 2% by addition of parameters. For PS, MC parameters showed a high ranking for building the model. For MACE, variables of the medical history showed more impact., Conclusions: MC per se cannot individually predict PS or MACE. However, when all MC parameters are integrated together with additional lesion-specific and history variables, a high individual predictive value can be achieved. This technique may be clinically helpful for risk stratification in the catheterization laboratory and improvement of classification systems in interventional cardiology.

Background: In patients with HER2-positive metastatic breast cancer (MBC), combined treatment of herceptin (H) and chemotherapy (CT) improves time to progression, response rates and survival compared with CT alone., Materials and Methods: We evaluated the safety and efficacy of weekly Docetaxel combined with weekly H as treatment in HER2 overexpressing MBC., Results: Preliminary toxicity data from 12 patients and 76 cycles of D and 80 cycles of H were analysed. No G3/4 toxicity was observed. The most frequent non-hematologic toxicities were fatigue (2 patients G2, 2 patients G1), dyspepsia (1 patients G2, 3 patients G1), diarrhea (1 patient G2, 3 patients G1), and nausea (1 patient G2, 3 patients G1). Six partial responses have been observed in 12 patients (ORR 50%)., Conclusions: The combination of weekly Docetaxel and Herceptin is well tolerated with significant anti-tumor activity.

Aims: Percutaneous transluminal coronary angioplasty (PTCA) has become the most widely used major intervention in western medicine. However, there is disparate use of this technique among different European countries and the U.S.A. In an attempt at quality assurance, the working group Coronary Circulation of the European Society of Cardiology has carried out a study on appropriateness, necessity, and performance of PTCA in Europe. The present paper reports on the procedural results of this survey., Methods: In a multicentre case-control study in Europe, 750 patients (544 men, 206 women) with documented vascular disease of the From the countries participating in the European Registry of Coronary Intervention, the three countries with the highest absolute PTCA volume (Germany, France, and the United Kingdom) and two randomly selected countries (Belgium and Italy) were chosen for investigation. In these countries, five centres were selected at random according to the following criteria: one centre with >1000, three centres with 300-1000, and one centre with <300 procedures per year. In each of these, 10 cases from the first half of 1997 were randomly identified and all pertinent documentation was collected., Results: In 250 cases, 325 stenoses were addressed as target lesions. Single vessel disease was present in 41%. History included stable angina in 49%, unstable angina in 32%, atypical chest pain in 6%, no anginal pain in 12%, and acute/subacute myocardial infarction in 13%. The percentage of patients with either positive stress test and/or unstable angina, acute/subacute infarction, previous infarction (within 6 months) or coronary revascularization amounted to 98%. Single vessel intervention accounted for 90%. In 41% balloon-only angioplasty was performed and in 54% at least one stent was implanted with considerable variation among countries. The use of other new devices amounted to only 3%. In 92%, the operators documented a successful procedure. Major complications (myocardial infarction, emergency bypass surgery, or death) were found in 4.8%., Conclusions: Based on scrutinized hospital and operator data, the present study revealed a satisfactorily high percentage of justifiable indications, an adequate procedural success rate, and an acceptably low complication rate. Further analysis by an expert panel will address appropriateness, necessity, and procedural performance of the individual cases., (Copyright 1999 The European Society of Cardiology.)

Aims: The purpose of this part of the INTERVENT project was (1) to redefine and individually predict post-procedural complications associated with coronary interventions, including alternative/adjunctive techniques to PTCA and (2) to employ the prognostic INTERVENT computer model to clarify the structural relationship between (pre)-procedural risk factors and post-procedural outcome., Methods and Results: In a multicentre study, 2500 data items of 455 consecutive patients (mean age: 61.1+/-8.3 years: 33-84 years) undergoing coronary interventions at three university centres were analysed. 80.4% of the patients were male, 16.7% had unstable angina, and 5.1%/10.1% acute/subacute myocardial infarction. There were multiple or multivessel stenoses in 16.0%, vessel bending >90 degrees in 14.5%, irregular vessel contours in 65.0%, moderate calcifications in 20.9%, moderate/severe vessel tortuosity in 53.2% and a diameter stenosis of 90%-99% in 44.4% of cases. The in-lab (out-of-lab) complications were: 0.4% (0.9%) death, 1.8% (0.2%) abrupt vessel closure with myocardial infarction and 5.5% (4.0) haemodynamic disorders., Conclusion: Computer algorithms derived from artificial intelligence were able to predict the individual risk of these post-procedural complications with an accuracy of >95% and to explain the structural relationship between risk factors and post-procedural complications. The most important prognostic factors were: heart failure (NYHA class), use of adjunctive/alternative techniques (rotablation, atherectomy, laser), acute coronary ischaemia, pre-existent cardiac medication, stenosis length, stenosis morphology (calcification), gender, age, amount of contrast agent and smoker status. Pre-medication with aspirin or other cardiac medication had a beneficial effect. Techniques, such as laser angioplasty or atherectomy were predictors for post-procedural complications. Single predictors alone were not able to describe the individual outcome completely.

Within the last years the prerequisite was prepared to develop a computerized tumor--patient documentation system including quality monitoring and oncological therapy recommendations for every day use. In medicine today, there is an increasing need for quality oriented low cost and transparent management--what is especially true in the field of oncology. The German Federal Authority of Health demands the documentation of all tumor disorders for the establishment of an cancer registry. For these reasons our study group established the program "OncoDoc" in cooperation with the laboratory for Artificial Intelligence of the University Bremen.