Thickness uniformity measurements and damage threshold tests of large-area GaAs/AlGaAs crystalline coatings for precision interferometry.

Precision interferometry is the leading method for extremely sensitive measurements in gravitational wave astronomy. Thermal noise of dielectric coatings poses a limitation to the sensitivity of these interferometers. To decrease coating thermal noise, new crystalline GaAs/AlGaAs multilayer mirrors have been developed. To date, the surface figure and thickness uniformity of these alternative low-loss coatings has not been investigated. Surface figure errors, for example, cause small angle scattering and thereby limit the sensitivity of an interferometer. Here we measure the surface figure of highly reflective, substrate-transferred, crystalline GaAs/AlGaAs coatings with a custom scanning reflectance system. We exploit the fact that the reflectivity varies with the thickness of the coating. To increase penetration into the coating, we used a 1550 nm laser on a highly reflective coating designed for a center wavelength of 1064 nm. The RMS thickness variation of a two inch optic was measured to be 0.41 ± 0.05 nm. This result is within 10% of the thickness uniformity, of 0.37 nm RMS, achieved with ion-beam sputtered coatings for the aLIGO detector. We additionally measured a lower limit of the laser induced damage threshold of 64 MW/cm 2 for GaAs/AlGaAs coatings at a wavelength of 1064 nm.

Matrix heater in the gravitational wave observatory GEO 600.

Large scale laser interferometric gravitational wave detectors (GWDs), such as GEO 600 require high quality optics to reach their design sensitivity. The inevitable surface imperfections, inhomogeneities, and light-absorption induced thermal lensing in the optics, can convert laser light from the fundamental mode to unwanted higher order modes, and pose challenges to the operation and sensitivity of the GWDs. Here we demonstrate the practical implementation of a thermal projection system which reduces those unwanted effects via targeted spatial heating of the optics. The thermal projector consists of 108 individually addressable heating elements which are imaged onto the beam splitter of GEO 600. We describe the optimization of the spatial heating profile and present the obtained results.

Ten-year results of intense dose-dense chemotherapy show superior survival compared with a conventional schedule in high-risk primary breast cancer: final results of AGO phase III iddEPC trial.

Background: Primary breast cancer (BC) patients with extensive axillary lymph-node involvement have a limited prognosis. The Arbeitsgemeinschaft fuer Gynaekologische Onkologie (AGO) trial compared intense dose-dense (idd) adjuvant chemotherapy with conventionally scheduled chemotherapy in high-risk BC patients. Here we report the final, 10-year follow-up analysis. Patients and methods: Enrolment took place between December 1998 and April 2003. A total of 1284 patients with 4 or more involved axillary lymph nodes were randomly assigned to receive 3 courses each of idd sequential epirubicin, paclitaxel and cyclophosphamide (iddEPC) q2w or standard epirubicin/cyclophosphamide followed by paclitaxel (EC â†’ P) q3w. Event-free survival (EFS) was the primary end point. Results: A total of 658 patients were assigned to receive iddEPC and 626 patients were assigned to receive EC â†’ P. The median duration of follow-up was 122 months. EFS was 47% (95% CI 43% to 52%) in the standard group and 56% (95% CI 52% to 60%) in the iddEPC group [hazard ratio (HR) 0.74, 95% CI 0.63-0.87; log-rank P = 0.00014, one-sided]. This benefit was independent of menopausal, hormone receptor or HER2 status. Ten-year overall survival (OS) was 59% (95% CI 55% to 63%) for patients in the standard group and 69% (95% CI 65% to 73%) for patients in the iddEPC group (HR = 0.72, 95% CI 0.60-0.87; log-rank P = 0.0007, two-sided). Nine versus two cases of secondary myeloid leukemia/myelodysplastic syndrome were observed in the iddEPC and the EC â†’ P arm, respectively. Conclusion: The previously reported OS benefit of iddEPC in comparison to conventionally dosed EC â†’ P has been further increased and achieved an absolute difference of 10% after 10 years of follow-up.

Huddle test measurement of a near Johnson noise limited geophone.

In this paper, the sensor noise of two geophone configurations (L-22D and L-4C geophones from Sercel with custom built amplifiers) was measured by performing two huddle tests. It is shown that the accuracy of the results can be significantly improved by performing the huddle test in a seismically quiet environment and by using a large number of reference sensors to remove the seismic foreground signal from the data. Using these two techniques, the measured sensor noise of the two geophone configurations matched the calculated predictions remarkably well in the bandwidth of interest (0.01 Hz-100 Hz). Low noise operational amplifiers OPA188 were utilized to amplify the L-4C geophone to give a sensor that was characterized to be near Johnson noise limited in the bandwidth of interest with a noise value of 10-11 m/Hz at 1 Hz.

German Adjuvant Intergroup Node-positive Study (GAIN): a phase III trial comparing two dose-dense regimens (iddEPC versus ddEC-PwX) in high-risk early breast cancer patients.

BACKGROUND: Dose-dense (dd) regimens are one of the preferred options for the adjuvant treatment of breast cancer patients with intermediate to high risk. The German Adjuvant Intergroup Node-positive trial aimed at optimizing intense dd (idd) strategies by evaluating drug combinations and the addition of capecitabine. PATIENTS AND METHODS: Women (aged 18 years and biologically <65 years) with histologically involved axillary lymph nodes were randomly assigned to receive three courses each of epirubicin (E) 150 mg/m2, paclitaxel (P) 225 mg/m2 and cyclophosphamide (C) 2500 mg/m2 (reduced to 2000 mg/m2 after recruitment of 1200 patients) q2w intravenously (i.v.) (iddEPC-regimen) or ddEC (E 112.5 mg/m2 + C 600 mg/m2, i.v. q2w for 4 cycles) followed by paclitaxel weekly (Pw 67.5 mg/m2 i.v. q8d for 10 weeks) plus capecitabine (X 2000 mg/m2 p.o. days 1-14, q22 for 4 cycles) (ddEC-PwX-regimen). Further randomization assigned patients to ibandronate for 2 years versus observation and to pegfilgrastim day 2 versus 4. RESULTS: From June 2004 to August 2008, 2994 patients were randomized to either iddEPC (N = 1498), or ddEC-PwX (N = 1496) and started treatment. Median age was 50 years; pN1 (37.8%), pN2 (35.3%); pN3 (26.9%); 46.4% were G3 tumors; 76.9% hormone receptor-positive and 22% HER2-positive. After a median follow-up of 74 months, 645 events and 383 deaths were recorded. Hematological adverse events grades 3-4 were more common with iddEPC (P < 0.001), nonhematological with ddEC-PwX (P = 0.04), even if the toxicity profile of the two regimens was different. At 5 years, estimated disease-free survival rates for ddEC-PwX and iddEPC were 81.7% [95% confidence interval (CI) 79.5-83.6] versus 80.2% (95% CI 78.0-82.2). Hazard ratio (HR)=0.95 (95% CI 0.81-1.11, log-rank P = 0.49). Five-year overall survival rates were 89.4% for ddEC-PwX (95% CI 87.7-91.0) and 89.0% for iddEPC (95% CI 87.2-90.6), HR = 0.85 (95% CI 0.69-1.04, log-rank P = 0.10). CONCLUSION: Adding capecitabine to ddEC-Pw did not improve outcome in comparison to iddEPC but increased toxicity and should not be recommended for further use.

ABC3 Consensus Commented from the Perspective of the German Guidelines: Third International Consensus Conference for Advanced Breast Cancer (ABC3), Lisbon, 07. 11. 2015.

The Third International Consensus Conference for Advanced Breast Cancer ABC3 on the diagnosis and treatment of advanced breast cancer was held in Lisbon from 5 to 7 November 2015. This year the focus was the treatment of metastatic breast cancer (stage IV) - including the patient perspectives. Important topics were questions relating to quality of life, the care for long-term survivors as well as the management of disease-related symptoms and treatment-based side effects. The use of standardised tools to assess individual treatment success and the benefits of new substances were important points for discussion. The diagnosis and treatment of inoperable locally advanced breast cancer were discussed two years ago during the ABC2 consensus 1. A working group of German breast cancer experts commented on the results of the ABC panellists, paying particular attention to the German guidelines (AGO, S3, DGHO) on the diagnosis and treatment of breast cancer 2, 3, 4, 5 in Germany.

Primary Therapy of Patients with Early Breast Cancer: Evidence, Controversies, Consensus: Opinions of German Specialists to the 14th St. Gallen International Breast Cancer Conference 2015 (Vienna 2015).

For the first time, this year's St. Gallen International Consensus Conference on the treatment of patients with primary breast cancer, which takes place every two years, was held not in St. Gallen (Switzerland) but - for logistical reasons - in Vienna (Austria) under its usual name. The 2015 St. Gallen International Consensus Conference was the 14th of its kind. As the international panel of the St. Gallen conference consists of experts from different countries, the consensus mirrors an international cross-section of opinions. From a German perspective, it was considered useful to translate the results of the votes of the St. Gallen conference into practical suggestions, particularly in light of the recently updated treatment guideline of the Gynecologic Oncology Group (AGO-Mamma 2015) in Germany. A German group consisting of 14 breast cancer experts, three of whom are members of the international St. Gallen panel, has therefore provided comments on the results of this year's votes at the 2015 St. Gallen Consensus Conference and their impact on clinical care in Germany. The 14th St. Gallen conference once again focused on surgery of the breast and the axilla, radio-oncologic and systemic treatment options for primary breast cancer depending on tumor biology, and the clinical use of multigene assays. The conference also considered targeted therapies for older and for younger patients, including the diagnosis/treatment of breast cancer during and after pregnancy and the preservation of fertility.

The Patient's Anastrozole Compliance to Therapy (PACT) Program: a randomized, in-practice study on the impact of a standardized information program on persistence and compliance to adjuvant endocrine therapy in postmenopausal women with early breast cancer.

BACKGROUND: Compliance and persistence are often overlooked in adjuvant breast cancer treatment. PATIENTS AND METHODS: PACT was a prospective, multicenter, randomized, open, parallel-group study assessing whether educational materials (EMs) enhanced compliance with aromatase inhibitor (AI) therapy in postmenopausal women with early, hormone-receptor-positive (HR+) breast cancer. The primary end points were compliance (proportion taking ≥ 80% anastrozole) at 12 months and persistence (proportion reporting anastrozole intake during the study period). RESULTS: Four thousand eight hundred and forty-four patients were randomly assigned 1:1 to receive standard therapy or standard therapy with EMs. There was no difference between arms in compliance (N = 2740; 88.5%/88.8%, respectively, P = 0.81) or persistence rates (N = 2740; 40.5%/43.0%, respectively, P = 0.18). Modified end point analyses found no differences in compliance between arms based on the classification of: (i) patients with missing documentation or follow-up visit <9 months as non-compliant (N = 4397, P = 0.15); (ii) patients with early (≤ 292 days) 12-month follow-up documentation excluded (N = 4091, P = 0.19); (iii) patients reaching ≥ 80% compliance during individual follow-up as compliant (N = 4397, P = 0.26). Modified persistence analyses found no difference between arms (N = 4397, P = 0.37). CONCLUSIONS: Addition of EMs to standard therapy did not significantly affect compliance and persistence with adjuvant anastrozole. CLINICALTRIALS ID: NCT00555867.

Chemotherapy for 70-Year-Old Women with Breast Cancer in Germany: A Survey by the German Breast Group.

Aim: Around half of all women in Germany with breast cancer are older than 65 and approximately one third of them is older than 70 years of age. In theory, the preferred therapeutic management of women with breast cancer aged 65 and above corresponds to that formulated for younger patients and complies with the S3 Guidelines and the therapy recommendations formulated by AGO. To study the current therapies used to treat women with breast cancer aged 70 and above in Germany, a survey of the clinics of the German Breast Group (GBG) was done. Method: An online survey was carried out with requests sent to 599 physicians registered as principal investigators in the database of the GBG. The 12-item questionnaire was used to investigate the systematic therapeutic management of 70-year-old patients in different settings. The indication for chemotherapy was taken as a given. Results: In a neoadjuvant setting, 62 % of physicians opted for anthracycline and taxane-based therapy as did 56.6 % of physicians in an adjuvant setting. One third of physicians preferred a taxane-based therapy with the anti-angiogenesis inhibitor bevacizumab as first-line therapy for primary metastatic cancer and after anthracycline-based therapy. Capecitabine (around 30 %) and navelbine (around 20 %) were proposed as second-line neoadjuvant and adjuvant therapies after prior anthracycline- and taxane-based therapy. Conclusion: The chemotherapy regimen prescribed for women with breast cancer aged 70 and above in Germany appears to be relatively standardised and corresponds to the recommendations given in the S3 Guidelines and by the AGO Breast Committee.

Influence of zoledronic acid on disseminated tumor cells in primary breast cancer patients.

BACKGROUND: The presence of disseminated tumor cells (DTCs) in bone marrow of patients with early breast cancer (EBC) has been correlated with increased risk of metastatic disease or locoregional relapse. Zoledronic acid (ZOL) treatment has reduced DTCs in the bone marrow of patients with EBC in several studies. This controlled study sought to confirm these observations. PATIENTS AND METHODS: Patients with EBC and DTC-positive bone marrow were randomized (N = 96) to treatment with ZOL plus adjuvant systemic therapy or adjuvant systemic therapy alone. The change in DTC numbers at 12 months versus baseline was measured. RESULTS: DTC-positive patients treated with ZOL were more likely to become DTC-negative after 12 months of treatment compared with the controls (67% versus 35%; P = 0.009). At 12 months, DTC counts decreased to a mean of 0.5 ± 0.8 DTCs in the ZOL group and to 0.9 ± 0.8 DTCs in the control group. In addition, ZOL was generally well tolerated. CONCLUSIONS: Treatment with ZOL improves elimination of DTCs. Further studies are needed to determine whether the reduction in DTCs by ZOL provides clinical benefit.

Intraperitoneal treatment with the trifunctional bispecific antibody Catumaxomab in patients with platinum-resistant epithelial ovarian cancer: a phase IIa study of the AGO Study Group.

OBJECTIVE: The aim of this study was to select the best catumaxomab regimen for further investigation in ovarian cancer based on confirmed tumour response. METHODS: Randomised open-label phase IIa study in women with platinum-resistant or -refractory epithelial ovarian cancer. Catumaxomab (6-hour intraperitoneal infusion on days 0, 3, 7 and 10) was administered at a low (10, 10, 10 and 10 µg) or high dose (10, 20, 50 and 100 µg). Responders were patients with either a complete (CR) or partial (PR) response. RESULTS: Forty-five patients were randomised to receive either low dose (23) or high dose (22). There were no responders in the low-dose versus one patient (5%) in the high-dose group with a PR. In the low-dose group, two patients (9%) had stable disease compared with five patients (23%) in the high-dose group. Catumaxomab was well tolerated and there was no difference between the dose groups in the incidence of treatment-induced adverse events, the most common of which were gastrointestinal and injection-site reactions. CONCLUSION: Catumaxomab had modest activity in platinum-resistant ovarian cancer. The high-dose regimen was associated with a slightly better therapeutic index than the low dose regimen.

PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel and CMF versus a standard-dosed epirubicin/cyclophosphamide followed by paclitaxel ± darbepoetin alfa in primary breast cancer--results at the time of surgery.

BACKGROUND: Preoperative chemotherapy is a recommended treatment of both primary operable and locally advanced breast cancer. Strategies to improve efficacy include the use of anthracyclines, taxanes, and intensified dose with bone marrow support. PATIENTS AND METHODS: Patients received neoadjuvant epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) followed by paclitaxel 175 mg/m(2) (EC→T), each 3-weekly for four cycles (n = 370), or epirubicin 150 mg/m(2) followed by paclitaxel 225 mg/m(2) with pegfilgrastim followed by CMF (cyclophosphamide 500 mg/m(2), methotrexate 40 mg/m(2), fluorouracil 600 mg/m(2)) on days 1 and 8 (E(dd)→T(dd)→CMF), each 2-weekly and for three cycles (n = 363). Patients were randomly allocated to either simultaneous darbepoetin alfa (DA) (n = 356) or none (n = 377). RESULTS: Pathological complete response (pCR) rate (breast) was higher with E(dd)→T(dd)→CMF, 18.7% versus 13.2% with EC→T; P = 0.043, ypT0/Tis; ypN0 was reported in 20.9% versus 14.3% respectively; P = 0.019. Patients with grade 3 tumors and negative hormone receptor status had a significantly higher pCR rate. Mean hemoglobin values maintained higher with DA (13.6 versus 12.6 g/dl). E(dd)→T(dd)→CMF regimen showed more grade 3-4 mucositis, sensory neuropathy, and neurological complaints. Thromboembolic events were more frequent on DA (3% versus 6%; P = 0.055). CONCLUSION: Dose-dense and -intensified neoadjuvant chemotherapy with E(dd)→T(dd)→CMF was potentially superior to EC→T in terms of pCR. Primary use of DA did not affect pCR.

PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel, and CMF versus a standard-dosed epirubicin-cyclophosphamide followed by paclitaxel with or without darbepoetin alfa in primary breast cancer--outcome on prognosis.

BACKGROUND: The objective of this study was to compare the effect of dose-intensified neoadjuvant chemotherapy with that of standard epirubicin plus cyclophosphamide followed by paclitaxel in combination with or without darbepoetin on survival in primary breast cancer. PATIENTS AND METHODS: A total of 733 patients received either four cycles of neoadjuvant epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) every 3 weeks followed by four cycles of paclitaxel 175 mg/m(2) every 3 weeks (EC→T), or three cycles of epirubicin 150 mg/m(2) every 2 weeks followed by three cycles of paclitaxel 225 mg/m(2) every 2 weeks followed by three cycles of combination chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (E(dd)→T(dd)→CMF). The patients were randomly assigned to receive darbepoetin or none. The primary objective was to demonstrate a superior disease-free survival (DFS) of E(dd)→T(dd)→CMF compared with EC→T. RESULTS: Estimated 3-year DFS was 75.8% with EC→T versus 78.8% with E(dd)→T(dd)→CMF [hazard ratio (HR) 1.14; P = 0.37] and overall survival (OS) 88.4% versus 91.5% (HR 1.26; P = 0.237). Three-year DFS was 74.3% with darbepoetin versus 80.0% without (HR 1.31; P = 0.061) and OS 88.0% versus 91.8% (HR 1.33; P = 0.139). Patients with a pathologically documented complete response [pathological complete response (pCR)] had a significantly better DFS compared with those without achieving a pCR (estimated 3-year DFS: 89.2% versus 74.9%; HR 2.27; P = 0.001). CONCLUSION: Neoadjuvant dose-intensified chemotherapy compared with standard chemotherapy did not improve DFS, whereas the addition of darbepoetin might have detrimental effects on DFS.

Combined NT-pro-BNP and CW-Doppler ultrasound cardiac output monitoring (USCOM) in epirubicin and liposomal doxorubicin therapy.

BACKGROUND: Chemotherapy with epirubicin is approved in women with breast cancer and is associated with a certain degree of cardiotoxicity. HYPOTHESIS: Epirubicin changes stroke volume, cardiac output and systemic vascular resistance, while liposomal doxorubicin does not. METHODS: 75 patients with HER-2-positive metastatic breast cancer were continuously measured with CW-Doppler ultrasound for stroke volume (SV), cardiac output (CO), and systemic vascular resistance (SVR) before, during and after drug infusion in combination with NT-pro-BNP before and 10 min after drug infusion. RESULTS: Epirubicin infusion increased stroke volume significantly in low-level NT-pro-BNP (62+/-23 ml vs. 74+/-29 ml, p=0.004) and high-level NT-pro-BNP (48+/-5 ml vs. 64+/-20 ml, p=0.131), while liposomal doxorubicin infusion increased stroke volume significantly in low-level NT-pro-BNP (54+/-16 ml vs. 67+/-22 ml, p=0.001) and high-level NT-pro-BNP (65+/-22 ml vs. 82+/-27 ml, p=0.001). Cardiac output was significantly increased in epirubicin (p=0.004) by 20% (NT-pro-BNP<125 pg/ml) and not significantly 38% (NT-pro-BNP>125 pg/ml; p=0.144), while in liposomal doxorubicin cardiac output was significantly increased by 23% (NT-pro-BNP<125 pg/ml; p=0.023) and 33% (NT-pro-BNP>125 pg/ml; p=0.001). In liposomal doxorubicin cardiac index was significantly increased by 26% (NT-pro-BNP<125 pg/ml; p=0.021) and 33% (NT-pro-BNP>125 pg/ml; p=0.0001). SVR was significantly reduced during and after epirubicin therapy. CONCLUSION: Using the CW-Doppler USCOM a different hemodynamic response to epirubicin vs. liposomal doxorubicin is evident. Epirubicin leads to a significant upregulation of stroke volume and cardiac output, which is even more pronounced in the high-level NT-pro-BNP group, while liposomal doxorubicin does not change immediate hemodynamics. No deterioration of cardiac function using the real-time CW-Doppler ultrasound USCOM or an increase in NT-pro-BNP levels was evident during epirubicin or liposomal doxorubicin therapy.

Simultaneous hemodynamic and serological cardiotoxicity monitoring during immunotherapy with trastuzumab.

BACKGROUND: Immunotherapy with trastuzumab (Herceptin), a selective HER-2(ErbB2)-antibody, is associated with a certain degree of cardiotoxicity. This study sought to evaluate the immediate hemodynamic response to trastuzumab with real-time CW-Doppler depending on the level of nt-pro-BNP (brain natriuretic peptide) as a possible marker of cardiotoxicity. METHODS: 48 patients with HER-2-positive metastatic breast cancer were continuously measured with CW-Doppler ultrasound for cardiac output (CO) and systemic vascular resistance (SVR) before, during and after drug infusion in combination with nt-pro-BNP before and 10 min after drug infusion. Depending on the nt-pro-BNP-levels <125 pg/ml (group A, n=34, 51+/-11 years) vs. nt-pro-BNP >125 pg/ml (group B, n=14, 63+/-7 years) two groups have been defined. RESULTS: Trastuzumab therapy did not change nt-pro-BNP immediately before (44+/-29 pg/ml) vs. after the infusion (45+/-32 pg/ml, n.s.) in the low-level as in the high level nt-pro-BNP group (231+/-356 pg/ml prior and 240+/-377 pg/ml, n.s.). Cardiac output remained stable during trastuzumab infusion, however cardiac output was significantly increased following the end of the infusion stronger in the high-level nt-pro-BNP group. Systemic vascular resistance prior to the trastuzumab infusion was higher in the high-level nt-pro-BNP group with significant decrement during and after the infusion. CONCLUSION: Combining real-time CW-Doppler ultrasound and nt-pro-BNP monitoring is feasible to monitor the immediate hemodynamic changes during and after trastuzumab infusion.

Detuned Twin-Signal-Recycling for ultrahigh-precision interferometers.

We propose a new interferometer technique for high-precision phase measurements such as those in gravitational wave detection. The technique utilizes a pair of optically coupled resonators that provide identical resonance conditions for the upper as well the lower phase modulation signal sidebands. This symmetry significantly reduces the noise spectral density in a wide frequency band compared with single-sideband recycling topologies of current and planned gravitational wave detectors. Furthermore, the application of squeezed states of light becomes less demanding.

[Improvement of breast cancer grading in punch biopsies: grading with the Ki-67 marker]. / Mammakarzinomgraduierung an Gewebestanzen: Objektivierung mit dem Proliferationsmarker Ki-67.

The grading of invasive breast cancers according to Bloom and Richardson (Nottingham modification) provides one of the most important prognostic factors in addition to size and the status of the lymph nodes. Diagnostic reproducibility has been problematic in daily practice as the required criteria for selection and extent of the grading area are frequently not present in the punch biopsies.A total of 346 cases were retrospectively used to compare routine grading from surgical preparations with an equivalently small sample from punch biopsies. In addition, a modified grading of these small samples was developed with Ki-67 immunochemistry and the measurement of core size. In the case of modified grading, 1-3 points were given for Ki-67 and average maximum core diameter. Tubule development was evaluated with 1 or 2 points. A comparison for recurrence free survival and total survival showed significant prognostic differences between 3-5 points (low risk) and 6-8 points (high risk) in uni- and multivariate analyses. The evaluation criteria for Nottingham-Bloom-Richardson grading in a small tissue sample, such as that from a punch biopsy, can hardly be fulfilled. In our series, prognostic value was only found for nodal negative cases. After modification using objective parameters such as nuclear size measurement and Ki-67 proliferation index, a small tissue sample can prove to be of significant prognostic value for nodal negative as well as nodal positive cases.

[Diagnosis and treatment of malignant ovarian tumors 2005: recommendations of the Kommission Ovar of the AGO]. / Diagnostik und Therapie maligner Ovarialtumoren 2005: Die Empfehlungen der Kommission Ovar der AGO.

Recommendations for diagnosis and treatment of malignant ovarian tumors with regard to the most recent data were worked out in a consensus process and valued by level of evidence (LoE) and grade of recommendation (GoR) of the Canadian Task Force for Preventive Health Care by the members of the Kommission Ovar der Arbeitsgemeinschaft für Gynäkologische Onkologie (AGO) in June 2005. A short version of these guidelines is presented.

[Epigenetic changes in breast cancer shown by aberrant promoter methylation]. / Epigenetische Alterationen im Mammakarzinom durch aberrante Promotormethylierung.

The aberrant methylation of cytosine residues in the promoter region of growth-regulatory genes is now recognized as an important inactivation mechanism in addition to deletion and mutation in the development and progression of cancer. Principally all pathways regulating proliferation and differentiation, which are perturbed in cancer cells, can be affected. In breast cancer epigenetic inactivation is a frequent and early event displaying great quantitative gene-specific differences during progression. The occurrence of specific aberrant methylation patterns is associated with the histological grade and subtype of mammary carcinoma biopsies.