No abstract

Endothelin-1 (ET-1) and its receptors (ET A R and ET B R), referred to as the endothelin (ET) axis, are overexpressed in breast carcinomas and appear to influence tumour growth and progression. The objective of this study was to determine the effect of expression of the ET axis in breast carcinomas on response to cytotoxic chemotherapy. The study included 44 patients with locally advanced breast cancer participating in a prospective phase III study evaluating high-dose neoadjuvant chemotherapy of epirubicin and cyclophosphamide. Expression of ET-1, ET A R and ET B R was determined by semiquantitative immunohistochemical analysis of breast cancer tissue from prechemotherapy tru-cut biopsies. Immunohistochemical staining was positive for ET-1 in 61.5%, for ET A R in 35% and for ET B R in 35.9% of breast carcinomas. Pathological response to chemotherapy was significantly decreased in ET A Rpositive patients (P ¼ 0.002). In total, 50% of ET A R-positive patients as compared to 7.7% of ET A R-negative patients attained pathologically 'no change'. Logistic regression confirmed ET A R as an independent predictive marker for pathological response (P ¼ 0.009). These data indicate that increased expression of ET A R in breast carcinomas is associated with resistance to chemotherapy. Determination of ET A R status may serve as a predictive marker for identifying patients less likely to be responsive to conventional chemotherapy.

We report about the 2-year results of a physician-based active cost management model for oncological therapies in a German OB/GYN university clinic. Over 2 years more than 4,000 oncological cycles were prospectively and individually analyzed regarding costs and reimbursement mode. Main aim was reducing costs without lowering cycle number and standard of care. Within two years pharmaceutical costs were reduced by 83.4% or 785,976.- EUR. All causes for a previous financial loss were identified and eliminated. Debts were paid back and employment of new staff and investments were possible. With this first active cost management model by and for physicians, oncological therapies can be performed cost covering even in a university clinic. Although developed for optimization of cost coverage of oncological therapies in Germany, this model is universally transferable.

Wax has been used for illustration purposes back to antiquity. Since the renaissance period human anatomy and different diseases have often been depicted in wax. During the last century the art of moulage preparation evolved to three-dimensional, realistic representations of diseased parts of the human body. Its heyday and wide spread distribution paralleled the growing independence of dermatology. Apart from few exceptions, most mouleurs did not permit access to their technique either to successors or the public. Just like other European hospitals, the Department of Dermatology at Kiel University houses a comprehensive collection of moulages dating back to a century. The 455 objects left today were collected by Professor Viktor Felix Karl Klingmüller (1870-1942) who was head of the department from 1906 to 1937. The mouleur Alfons Kröner from Breslau who died 1937 supplied most (354) of the wax models. Highly esteemed at his time, Kröner was quite secretive about his art of moulagig. 35 of his moulages bear the abbreviation "DRP" standing for Deutsches Reichspatent (German patent); Kröner was granted a patent in 1902. In his patent application both wax mixtures and technical procedure of moulaging are described in great detail. Kröner, similarly to Jules Baretta (Paris), coloured his moulages at the back of the wax layers. Applying for a patent demonstrates his effort to meet increasing commercial pressure among suppliers of teaching aids at that time. Knowledge of individual technical procedures is essential for medical history as well as proper restauration of moulages as they continually deteriorate with time. Because of their three-dimensional and realistic disease representations, moulages still compare well to modern media used today. Consequently, the "dying of moulages" concerning the wax objects themselves as well as public or medical interest has to be stopped to preserve moulages for future generations.

Even in elderly patients, greater consideration is now being given to tumor volume reduction in locally advanced breast cancer, with increased subsequent breast-conserving surgery. Neoadjuvant endocrine therapy offers the possibility of testing therapeutic efficacy in vivo, which is of great importance for optimal adjuvant treatment. Resulting therapy modifications can be expected to increase disease-free as well as overall survival. Recent results indicate that remission rates with primary chemotherapy are significantly lower in receptor-positive than in receptor-negative breast cancer and that efficacy parameters in receptor-positive tumors tend to favor primary endocrine therapy, highlighting the increased importance of this type of treatment. Aromatase inhibitors are superior to tamoxifen in terms of clinical response as well as breast conservation rate. Results from a small number of studies suggest that prolonged preoperative aromatase inhibitor therapy for up to 12 months can increase the rate of clinical and pathological complete remissions. In conclusion, primary endocrine therapy is a valid therapeutic option for postmenopausal patients with locally advanced hormone receptor-positive breast cancer and significant comorbidity, increased risk of complications with regard to anesthesia and surgery, desire for breast-conserving surgery and/or reduced suitability for chemotherapy, as well as in very old patients.

No abstract

The most common chemotherapeutic agents in the treatment of breast cancer are anthracyclines and taxanes. The major dose-limiting toxicities associated with these agents are myelosuppression and associated febrile neutropenia (FN). FN can significantly impact the ability to deliver full-dose chemotherapy on schedule and as a result may increase the risk of disease recurrence and eventual disease-related mortality. The use of granulocyte colony stimulating factors (G-CSFs) significantly improves the management of FN, both in a therapeutic and in a prophylactic approach. Nevertheless, the high cost of these agents limits their widespread prophylactic use. Therefore, the identification of patients who are at a higher risk of developing FN and who will benefit from the prophylactic use of G-CSFs has become the subject of several clinical and cost-effectiveness studies. Recently, new data have been accumulated concerning the risk of FN in different chemotherapy regimens, and different risk models have been developed to assess the neutropenic risk with all its complications. This article reviews and summarizes cutting-edge, disease-specific data as well as national and international guidelines regarding the use of G-CSFs to prevent chemotherapy-induced FN, with focus on the treatment of breast cancer.

534 Background: Chemo N0 was the first multicenter randomized clinical trial in breast cancer using biomarkers uPA/PAI-1 for risk stratification and chemotherapy selection. Chemo N0 validated uPA/PAI-1 as clinically relevant parameters for risk assessment in N0 breast cancer. About 50% of N0 patients have low uPA/PAI-1 in their primary tumor with excellent 5-year OS (>95%), even without adjuvant therapy. Patients with high uPA/PAI-1 benefit from adjuvant chemotherapy. We evaluated whether biomarkers can predict outcome more accurately than a computer-program. Methods: In Chemo N0, patients (n=689, 1993–98) were stratified according to uPA/PAI-1: High-risk patients were randomized (6x CMF vs. observation), low-risk patients observed. Retrospectively, we divided recruited patients into two groups (chemotherapy vs. no adjuvant therapy) and stratified using uPA/PAI-1 (low vs. high). Individual 10-year OS was calculated by www.adjuvantonline.org (Version 7.0); these estimated values were compared to the observed 10-year OS in Chemo N0. Results: 81/151 patients with already available complete follow-up data 10 years after trial start have 10-year OS results. Median 10-year OS estimated by Adjuvant Online was 77.1% (median 78.6%) taking into account administered adjuvant therapy. 10-year Chemo N0 follow-up revealed an observed 10-year OS of 66.7% (27/81 deceased). 64/81 did not receive chemotherapy: In high-risk untreated patients (n=22), 10-year OS was 54.6% vs. estimated 75.0%. In CMF-treated patients (all high-risk, n=17), observed OS was 58.8% vs. estimated 74.6%. Conclusions: For the first time, risk assessment by novel biomarkers is compared to that by Adjuvant Online in data from a randomized clinical trial. In patients with high uPA/PAI-1, the individual 10-year OS calculated by Adjuvant Online seems to be underestimated compared to observed patient outcome. Further follow-up data will show whether uPA/PAI-1 can predict the individual course of disease more precisely than a computer-program based on large clinical data sets. Final Chemo N0 10-year follow-up is currently being completed. No significant financial relationships to disclose.