Prädiktive Biomarker beim ER+/HER2 - Mammakarzinom - Diskrepanz zwischen S3-Leitlinie, AGO-Empfehlung und St.-Gallen-Expertenmeinung

Auch fur die Behandlung von Brustkrebs bilden Leitlinien und Expertenkonsensus eine unverzichtbare Basis fur eine evidenzbasierte Auswahl der Therapie. In Deutschland sind dies unter anderem die S3-Leitlinie der Deutschen Krebsgesellschaft, die Leitlinien der Arbeitsgemeinschaft Gynakologische Onkologie und der Expertenkonsensus von St. Gallen. Durch sie wurden einheitliche Behandlungsstrategien erreicht und so wesentliche Fortschritte bei der Behandlung des Mammakarzinoms mit ermoglicht. Fur die Entscheidung, ob Patientinnen mit einem luminalen Mammakarzinom der mittleren Risikogruppe mit einer chemo-endokrinen Therapie behandelt werden sollten oder ob eine einfache Hormontherapie ausreich…

Rho GTPases in human breast tumours: expression and mutation analyses and correlation with clinical parameters

In the present study, we addressed the question of a putative relevance of Rho proteins in tumour progression by analysing their expression on protein and mRNA level in breast tumours. We show that the level of RhoA, RhoB, Rac1 and Cdc42 protein is largely enhanced in all tumour samples analysed (n=15) as compared to normal tissues originating from the same individual. The same is true for 32P-ADP-ribosylation of Rho proteins which is catalysed by Clostridium botulinum exoenzyme C3. Also the amount of Rho-GDI and ERK2 as well as the level of overall 32P-GTP binding acvitity was tumour-specific elevated, yet to a lower extent than Rho proteins. Although the amount of Rho proteins was enhance…

Charakteristika und Überlebensanalyse der Patienten mit asymptomatischen Hirnmetastasen eines Mammakarzinoms

Prognostische Bedeutung einer Diabeteserkrankung beim Endometriumkarzinom

Objective: The purposes of this study were to analyze the relationship between clinical and pathological risk factors in endometrial cancer and additional diabetes mellitus and to clarify the correlation between additional diabetes mellitus and survival of patients with this disease. - Material and methods: This analyze included 181 patients with endometrial carcinoma who were treated between 1985 and 1995 at the University hospital Mainz. Patients with sarcoma were excluded. For statistical analysis a Χ 2 -test was performed for univariat analysis. A Kaplan-Meier procedure was performed for over all survival and disease free interval and COX-Regression for multivariate analysis of independ…

Patient Reported Outcome in metastatic breast cancer and platinum-resistant recurrent ovarian cancer treated with metronomic cyclophosphamide ± methotrexate: PROmetronomic - FoR.UM 19-02193

Immunohistochemical analysis of IGCK expression in early breast cancer patients treated with adjuvant chemotherapy

253 PFS of elderly ovarian cancer patients might be predicted by G-8 geriatric screening tool – results of a retrospective cohort study

Introduction/Background* The aim of this study was to evaluate the impact of the preoperative global health status on the prognosis of patients with ovarian cancer (OC) older than 60 years, who received cytoreductive surgery. Methodology G-8 geriatric screening tool (G-8 score), Lee Schonberg prognostic index, Eastern Cooperative Oncology Group (ECOG) performance status and Charlson Comorbidity Index (CCI) were determined retrospectively in a consecutive cohort of elderly patients with OC. Univariate and multivariate Cox regression analyses and Kaplan-Meier method were performed to analyze the impact of the preoperative global health status on survival. Result(s)* 116 patients entered the s…

Immunoglobulin Kappa C Has Independent Prognostic Significance in Node-Negative Breast Cancer.

Abstract Background: Utilizing microarray based gene-expression analysis of fresh-frozen tissue we could recently demonstrate the prognostic impact of a B cell metagene in node-negative breast cancer (Cancer Res 68: 5405-5413, 2008). In the present study we investigated the prognostic significance of immunoglobulin kappa c (IGKC) in formalin-fixed paraffin embedded (FFPE) breast cancer specimens of 363 node-negative breast cancer patients which were not treated in the adjuvant setting.Methods: RT-PCR was used to analyze mRNA expression of IGKC in FFPE tissue of 363 patients with node-negative breast cancer. Additionally to IGKC we examined the prognostic impact of age, histological grade, t…

KDM5B and CBX5 as potential tumor-associated immunogenic antigens in triple-negative breast cancer (TNBC)

345 Comparison of cisplatin and mitomycin/5-FU as radiosensitizers in the treatment of vulvar cancer – results of a single institutional cohort study

Introduction/Background* Treatment of vulvar cancer contains surgery if applicable and often primary or neo-/adjuvant chemoradiation. Cisplatin and Mitomycin/5-FU are widely used radiosensitizers in vulvar cancer, although evidence is limited. We retrospectively investigated both radiosensitizers for outcome and toxicity. Methodology We screened the archive for patients treated with chemoradiation for pathologically-confirmed squamous cell cancer of the vulva between 01/2010 – 02/2021 at our institution. The impact of both radiosensitizers on prognosis was compared using Kaplan-Meier method and Cox-Regression analysis. Result(s)* 127 patients with vulvar cancer were screened. 24 patients re…

A role for Rho in receptor- and G protein-stimulated phospholipase C Reduction in phosphatidylinositol 4,5-bisphosphate by Clostridium difficile toxin B

Receptors coupled to heterotrimeric guanine nucleotide-binding proteins (G proteins) activate phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2)-hydrolyzing phospholipase C (PLC) enzymes by activated alpha of free beta gamma subunits of the relevant G proteins. To study whether low molecular weight G proteins of the Rho family are involved in receptor signaling to PLC, we examined the effect of Clostridium difficile toxin B, which glucosylates and thereby inactivates Rho proteins, on the regulation of PLC activity in human embryonic kidney (HEK) cells stably expressing the m3 muscarinic acetylcholine receptor (mAChR) subtype. Toxin B treatment of HEK cells did not affect basal PLC activi…

Evaluation der Sprachaufgaben des sozialpädiatrischen Entwicklungsscreenings für Schuleingangsuntersuchungen (SOPESS): Ergebnisse der prospektiven Kindergesundheitsstudie ikidS

Zusammenfassung Hintergrund Eine frühe Diagnostik und Behandlung von Entwicklungsstörungen vor der Einschulung ist für den weiteren Bildungserfolg maßgeblich. Deshalb wurde das Sozialpädiatrische Entwicklungsscreening für Schuleingangsuntersuchungen (SOPESS) konzipiert und in mehreren Bundesländern flächendeckend eingeführt. Fragestellung Wir untersuchten die Zusammenhänge zwischen den Screening-Ergebnissen der SOPESS-Sprachaufgaben vor der Einschulung und den schulischen Sprachkompetenzen am Ende der ersten Klasse als Teil einer umfassenden Evaluation des SOPESS. Methoden Daten der rheinland-pfälzischen Schuleingangsuntersuchung und der prospektiven Kindergesundheitsstudie ikidS wurden zus…

Dokumentationsverhalten in der eHealth-Anwendung CANKADO und Auswirkung auf beobachtete Nebenwirkungen - eine explorative Analyse der PreCycle-Studie

Skin-reducing Mastectomy with Primary Implant Reconstruction

Background: We present a series of skin-sparing mastectomies (SSMs) with skin reduction and immediate breast reconstruction to treat large and ptotic breasts. The technique combines oncological mastectomy with immediate subpectoral implant placement as a single-step procedure. Methods: Data was collected from a prospective database from February 2009 to April 2011. A total of 24 patients with macromastia or pronounced ptosis fulfilled the criteria for skin-saving mastectomy. All operations were carried out as a single-step procedure with adaptation of the contralateral breast by reduction mastopexy. Results: A total of 27 SSMs were performed in 24 patients. The mean implant volume was 265 c…

Wertigkeit der Abradathistologie von Endometriumkarzinomen

Objective: We compared immunohistological examination of endometrium biopsy specimen with the results of the immunohistological examination of tumor specimen to analyse the valence of this preoperative examination according to the clinico-pathological findings and overall-survival. Material and Method: Between 1985 and 1995 193 women were treated of an endometrial carcinoma at the University hospital Mainz. In this group we evaluated 41 patients with enough preoperative endometrial biopsy material for a retrospective immunohistochemical analysis and complete follow-up data. The materials from diagnostic curettage were stained and analysed for oestrogen and progesterone receptor status and f…

A randomized study of tucatinib (ONT-380) vs. placebo in combination with capecitabine and trastuzumab in patients with pretreated HER2-pos. metastatic breast cancer: HER2CLIMB

237 Selected global health assessment tools significantly predict postoperative clinical outcome in elderly patients with ovarian cancer

Introduction/Background* This study evaluated the impact of the global health status on the rate of postoperative clinical complications in patients with ovarian cancer (OC) older than 60 years. Methodology Selected global health status assessment tools were retrospectively determined in a cohort of OC patients older than 60 years, treated at our institution between 2008 and 2019. The primary outcome was the incidence and type of postoperative clinical complications in accordance with the Veteran Affairs’ National Surgical Quality Improvement Program (NSQIP). Differences in binary and ordinal variables between independent groups were analyzed by the chi-square test. Furthermore, rank correl…

Comparison of Prognostic Signatures in Node-Negative Tamoxifen-Treated Breast Cancer Patients.

Abstract Background: A number of molecular signatures have been published to aid breast cancer prognosis and therapy response prediction. A 76-gene signature has been developed in a node-negative patient cohort that did not receive systemic therapy.1 Another prognostic 97-gene signature measures predominantly proliferation-associated genes.2 Finally, a 21-gene signature has been developed for node-negative and estrogen receptor–positive breast cancer patients treated with tamoxifen in the adjuvant setting.3 Here we compare the prognostic performance of all three published algorithms in a cohort of 189 node-negative breast cancer patients treated with tamoxifen.Materials and Methods: Fresh-f…

Pazopanib (GW786034) and cyclophosphamide in patients with platinum-resistant, recurrent, pre-treated ovarian cancer - Results of the PACOVAR-trial.

Abstract Purpose The prognosis is poor for patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC). Evidence suggests that antiangiogenic treatment modalities could play a major role in EOC. A combined therapy consisting of the investigational oral antiangiogenic agent pazopanib and metronomic oral cyclophosphamide may offer a well-tolerable treatment option to patients with recurrent, previously treated EOC. Patients and methods This study was designed as a multicenter phase I trial evaluating the optimal dose as well as activity and tolerability of pazopanib with metronomic cyclophosphamide in the treatment of patients with recurrent, platinum-resistant, previously tre…

Combination of osteopontin and activated leukocyte cell adhesion molecule as potent prognostic discriminators in HER2- and ER-negative breast cancer.

Background: To analyse the discriminative impact of osteopontin (OPN) and activated leukocyte cell adhesion molecule (ALCAM), combined with human epidermal growth factor 2 (HER2) and oestrogen receptor (ER) in breast cancer. Methods: Osteopontin, ALCAM, HER2 and ER mRNA expression in breast cancer tissues of 481 patients were analysed (mRNA microarray analysis, kinetic RT–PCR). Hierarchical clustering was performed in training cohort A (N=100, adjuvant treatment) and validation cohorts B (N=200, no adjuvant treatment, low-risk) and C (N=181, adjuvant treatment, high-risk). Results: Negative/low ER and HER2, high OPN and low ALCAM mRNA expression helped to identify patients at particularly h…

Phase IB study of the EpCAM antibody adecatumumab combined with docetaxel in patients with epcampositive relapsed or refractory advanced-stage breast cancer

Background: Targeted therapy options in HER2-negative breast cancer are limited. This open-label, multicenter phase IB dose-escalation trial was conducted to determine safety, tolerability, and antitumor activity of a combination of docetaxel (Taxotere) and increasing doses of adecatumumab, a human IgG1 antibody targeting epithelial cell adhesion molecule (EpCAM), in EpCAM-positive relapsed or primary refractory advanced-stage breast cancer. Patients and methods: Patients pretreated with up to four prior chemotherapy regimens received increasing adecatumumab doses either every 3 weeks (q3w) or weekly (qw) combined with docetaxel (100 mg/m 2 q3w). Primary end points were safety and tolerabil…

Different T-cell Receptor (TCR) Zeta Chain Expression in Cervical Cancer and its Precursor Lesions

OBJECTIVE Cervical cancer is associated with infection of epithelial cells with the human papillomavirus (HPV) type 16 and HPV18. A functional signalling machinery in T-cells is required in order to successfully fight and eradicate HPV16+ transformed epithelial cells. One of the key signalling molecules associated with the T-cell receptor (TCR) is the homodimeric zeta chain molecule. MATERIAL AND METHODS 28 formalin fixed und paraffin embedded samples of cervical tissue with cervical intraepithelial lesions CIN I (n = 3), CIN III (n = 7), invasive cervical carcinoma (CC) (n = 13) and normal cervical tissue (n = 5) has been evaluated for HPV-PCR und zeta chain immunohistochemistry. For immun…

Anti-hormonal maintenance treatment with or without the CDK4/6 inhibitor ribociclib after first line chemotherapy in hormone receptor positive/HER2 negative metastatic breast cancer: A phase II trial (AMICA) GBG 97

70 Patient reported outcome in platinum-resistant recurrent ovarian cancer and metastatic breast cancer treated with metronomic chemotherapy

Introduction/Background* In the treatment of both platinum-resistant recurrent ovarian cancer (ROC) and metastatic breast cancer (MBC), symptom control and maintenance of quality of life (QoL) play a crucial role. In the advanced stage of disease, metronomic chemotherapy (MCT) may be a favourable treatment option. The aim of this study is to assess the QoL of heavily pretreated patients with ROC and MBC treated with MCT. Methodology PROmetronomic, FoR.UM 19-02193, is a monocentric, open-label, single-arm observational study to assess health-related patient-reported outcome data in ROC and MBC patients treated with MCT (cyclophosphamide 50 mg p.o. daily ± methotrexate 2.5 mg p.o. every other…

Prospective randomized comparison of conventional instruments and the Harmonic Focus(®) device in breast-conserving therapy for primary breast cancer.

Abstract Background In recent years, surgeons have utilized Harmonic instruments to perform breast cancer resection. Retrospective and prospective studies have demonstrated that the use of this surgical device for mastectomy and axillary dissection can reduce perioperative blood loss, seroma formation, and duration and total amount of drainage. No study has analyzed the feasibility of Harmonic instruments in breast-conserving surgery. We conducted a prospective, randomized clinical trial comparing Harmonic instrument and conventional surgery in the performance of breast-conserving surgery and axillary procedures to determine differences in surgical procedures, postoperative outcome, and com…

Role of urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) for prognosis in endometrial cancer

Abstract Background. Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) contribute to the invasiveness of many carcinomas. Here, we studied a possible association between cytosolic uPA and PA-1 concentrations in tumor tissue with prognosis in patients with endometrial cancer. Methods. Cytosolic concentrations of uPA and PAI-1 were determined in 69 primary endothelial adenocarcinomas using an enzyme-linked immunoassay (ELISA). A possible influence of uPA and PAI-1 was studied by multivariate Cox regression adjusting for the established clinical prognostic factors FIGO-stage, grading, depth of invasion, diabetes mellitus and age. Results. Both uPA ( …

Long-term outcome prediction by clinicopathological risk classification algorithms in node-negative breast cancer--comparison between Adjuvant!, St Gallen, and a novel risk algorithm used in the prospective randomized Node-Negative-Breast Cancer-3 (NNBC-3) trial.

Background: Defining risk categories in breast cancer is of considerable clinical significance. We have developed a novel risk classification algorithm and compared its prognostic utility to the Web-based tool Adjuvant! and to the St Gallen risk classification. Patients and methods: After a median follow-up of 10 years, we retrospectively analyzed 410 consecutive node-negative breast cancer patients who had not received adjuvant systemic therapy. High risk was defined by any of the following criteria: (i) age 2 cm. All patients were also characterized using Adjuvant! and the St Gallen 2007 risk categories. We analyzed disease-free survival (DFS) and overall survival (OS). Results: The Node-…

246 Survival of elderly patients with endometrial cancer – predicted by preoperative G-8 geriatric screening tool

Introduction/Background* We evaluated the prognostic impact of various global health assessment tools in accordance to conventional prognostic factors in patients with endometrial cancer (EC) older than 60 years. Methodology G-8 geriatric screening tool (G-8 geriatric score), Lee Schonberg prognostic index (Lee-Index), Charlson Comorbidity Index (CCI) and American Society of Anesthesiologists (ASA-PS) – Physical Status System were retrospectively determined in a consecutive cohort of elderly patients with EC. Univariate and multivariate Cox regression analyses and Kaplan-Meier method were performed to determine the impact of the global health assessment tools on progression free survival (P…

86P Patients (pts) preference for different administration methods of trastuzumab (T) in pts with HER2+ early breast cancer (BC) treated within the GAIN-2 trial

The pharmacological rationale for combining muscarinic receptor antagonists and beta-adrenoceptor agonists in the treatment of airway and bladder disease

Highlights • Muscarinic receptors increase smooth muscle tone in airways and urinary bladder. • β-Adrenoceptors relax smooth muscle tone and oppose muscarinic contraction. • Opposition involves transmitter release, signal transduction and receptor expression. • This supports the combined use of muscarinic antagonists and β-adrenoceptor agonists.

A retrospective analysis of immunohistochemical determined IRF4 (interferon regulating factor 4) expression in a consecutive cohort of 114 ovarian cancer patients

Use of primary and secondary pegfilgrastim prophylaxis for reducing incidence of neutropenia: Findings from a large study in German clinical practice (PROTECT)

(TA)MUC1 as a potential new target for breast cancer therapy

Mental health and health-related quality of life in preschool-aged childhood cancer survivors. Results of the prospective cohort study ikidS-OEVA.

Objectives Long-term survivors of childhood cancer are at increased risk for sequelae such as poor mental health (MH) or impaired health-related quality of life (HrQoL). We aimed to evaluate early adverse effects on MH and HrQoL in young childhood cancer survivors (YCCS) before school entry. Methods In a nationwide prospective cohort study, children with cancer other than brain tumors diagnosed at preschool age and completed cancer treatments were identified from the German Childhood Cancer Registry. The comparison group was children of the same age without a cancer diagnosis who participated in the prospective population-based health survey ikidS. MH problems and HrQoL were assessed by par…

88MO T-cell responses induced by an individualized neoantigen specific immune therapy in post (neo)adjuvant patients with triple negative breast cancer

A Novel Multigene Assay in Clinical Practice - Performance and Impact On Clinical Decisions

Inhibition of Receptor Signaling to Phospholipase D by Clostridium difficile Toxin B

Rho proteins have been reported to activate phospholipase D (PLD) in in vitro preparations. To examine the role of Rho proteins in receptor signaling to PLD, we studied the effect of Clostridium difficile toxin B, which glucosylates Rho proteins, on the regulation of PLD activity in human embryonic kidney (HEK) cells stably expressing the m3 muscarinic acetylcholine receptor (mAChR). Toxin B treatment of HEK cells potently and efficiently blocked mAChR-stimulated PLD. In contrast, basal and phorbol ester-stimulated PLD activities were not or only slightly reduced. Cytochalasin B and Clostridium botulinum C2 toxin, mimicking the effect of toxin B on the actin cytoskeleton but without involvi…

The EndoPredict score provides prognostic information on late distant metastases in ER+/HER2− breast cancer patients

Background: ER þ/HER2 � breast cancers have a proclivity for late recurrence. A personalised estimate of relapse risk after 5 years of endocrine treatment can improve patient selection for extended hormonal therapy. Methods: A total of 1702 postmenopausal ER þ/HER2 � breast cancer patients from two adjuvant phase III trials (ABCSG6, ABCSG8) treated with 5 years of endocrine therapy participated in this study. The multigene test EndoPredict (EP) and the EPclin score (which combines EP with tumour size and nodal status) were predefined in independent training cohorts. All patients were retrospectively assigned to risk categories based on gene expression and on clinical parameters. The primary…

Progression of breast tumors is accompanied by a decrease in expression of the Rho guanine exchange factor Tiam1

In this study, we investigated the expression level of Ras-homologous (Rho) GTPases and the Rho guanine exchange factor (GEF) T-cell lymphoma invasion and metastasis 1 (Tiam1) in breast tumor specimens (n=106) by immunohistochemistry. Rho and Rho-GEF expression scores were compared to clinically established diagnostic and prognostic parameters. We found that RhoA and RhoB scores slightly increased with tumor grade, whereas the Rac1 score remained unaffected. The most significant effects were observed for the Rac1-specific GEF Tiam1. Tiam1 expression scores significantly decreased with the increase in tumor grade, tumor spreading and proliferation. Furthermore, Tiam1 expression was inversely…

EndoPredict improves the prognostic classification derived from common clinical guidelines in ER-positive, HER2-negative early breast cancer

Background In early estrogen receptor (ER)-positive/HER2-negative breast cancer, the decision to administer chemotherapy is largely based on prognostic criteria. The combined molecular/clinical EndoPredict test (EPclin) has been validated to accurately assess prognosis in this population. In this study, the clinical relevance of EPclin in relation to well-established clinical guidelines is assessed. Patients and methods We assigned risk groups to 1702 ER-positive/HER2-negative postmenopausal women from two large phase III trials treated only with endocrine therapy. Prognosis was assigned according to National Comprehensive Cancer Center Network-, German S3-, St Gallen guidelines and the EPc…

Validierung des Breast-GPA Scores bei Patientinnen mit Hirnmetastasen eines Mammakarzinoms im BMBC-Register (GBG-79)

Specific Inhibition of Phorbol Ester-stimulated Phospholipase D by Clostridium sordellii Lethal Toxin and Clostridium difficile Toxin B-1470 in HEK-293 Cells

Activation of m3 muscarinic acetylcholine receptor (mAChR), stably expressed in human embryonic kidney (HEK)-293 cells, leads to phospholipase D (PLD) stimulation, a process apparently involving Rho GTPases, as shown by studies with Clostridium botulinum C3 exoenzyme and Clostridium difficile toxin B (TcdB). Direct activation of protein kinase C (PKC) by phorbol esters, such as phorbol 12-myristate 13-acetate (PMA), also induces PLD stimulation, which is additive to the mAChR action and which is only poorly sensitive to inactivation of Rho proteins by TcdB. To study whether Ras-like GTPases are involved in PLD regulation, we studied the effects of the TcdB variant TcdB-1470 and Clostridium …

Molecular Basis for the Regulation of Cell Fate by the Lethal (2) Giant Larvae Tumour Suppressor Gene of Drosophila Melanogaster

Tumour suppressor genes act as recessive determinants of cancer. Their function is required for normal cell growth and differentiation during development. When both alleles of these developmental genes are inactivated, cell growth becomes unrestricted. In Drosophila, a series of genes have been identified which when mutated produce tissue-specific tumours. Of these the lethal(2)giant larvae (l(2)gl) gene is the best studied. Homozygous l(2)gl mutations cause the development of malignant tumours in the brain and the imaginal discs. Genomic DNA from the l(2)gl locus has been cloned, introduced back into l(2)gl mutant animals by P-element-mediated transformation and shown to restore normal dev…

Ibandronate Shows Marked Pain Relief and a Favorable Renal Safety Profile – Updated Results of a Non Interventional Study in Breast Cancer Patients with Metastatic Bone Disease.

Abstract Background: Bisphosphonates (BP), the current standard of care for patients with metastatic bone disease (MBD) due to breast cancer (BC), effectively reduce the incidence of skeletal related events (SRE) and the severity of bone pain. However, BP treatment may adversely affect kidney function and thus renal safety is a key determinant of BP risk/benefit assessment. In randomized clinical trials (RCT), Ibandronate (IBA), a third generation amino-BP available in IV and oral formulations, has demonstrated sustained effects on SRE and bone pain with a low incidence of renal adverse events. To verify those results under real life conditions, a large-scale non interventional study (NIS) …

Tyrosine-phosphorylation-dependent and Rho-protein-mediated control of cellular phosphatidylinositol 4,5-bisphosphate levels

The polyphosphoinositide PtdIns(4,5)P2, best known as a substrate for phospholipase C isozymes, has recently been recognized to be involved in a variety of other cellular processes. The aim of this study was to examine whether the cellular levels of this versatile phospholipid are controlled by tyrosine phosphorylation. The studies were performed in human embryonic kidney (HEK)-293 cells stably expressing the M3 muscarinic acetylcholine receptor. Inhibition of tyrosine phosphatases by pervanadate induced an up-to-approx.-2.5-fold increase in the total cellular level of PtdIns(4,5)P2, which was both time- and concentration-dependent. In contrast, the tyrosine kinase inhibitors, genistein and…

317 Role of integrins in the metastatic spread of high-grade serous ovarian cancer

Introduction/Background* In high-grade serous ovarian cancer (HGSOC) an early intraperitoneal metastatic spread is common which determines the therapeutical approach and prognosis. Integrins may be involved in metastatic spread of HGSOC. In this study, integrin expression was examined in primary tumour and metastases of HGSOC. Methodology The expression of integrin α2, α4, α5, α6, and β1 was assessed by immunostaining in tumour samples of the ovary, omentum, and peritoneum of each patient. Differences in integrin expression among tumour localisations and their association with clinicopathological parameters were examined by Fisher’s exact test. The impact of integrin expression on progressi…

Targeted mRNA sequencing of small formalin-fixed and paraffin-embedded breast cancer samples for the quantification of immune and cancer-related genes

Role of the progesterone receptor for paclitaxel resistance in primary breast cancer

Paclitaxel plays an important role in the treatment of primary breast cancer. However, a substantial proportion of patients treated with paclitaxel does not appear to derive any benefit from this therapy. We performed a prospective study using tumour cells isolated from 50 primary breast carcinomas. Sensitivity of primary tumour cells to paclitaxel was determined in a clinically relevant range of concentrations (0.85-27.2 microg ml(-1) paclitaxel) using an ATP assay. Chemosensitivity data were used to study a possible association with immunohistochemically determined oestrogen and progesterone receptor (ER and PR) status, as well as histopathological parameters. Progesterone receptor (PR) m…

Treatment and outcomes of patients in the Brain Metastases in Breast Cancer Network Registry

Brain metastases (BMs) have a major impact on life expectancy and quality of life for many breast cancer patients. Knowledge about treatment patterns and outcomes is limited.We analysed clinical data of 1712 patients diagnosed with BMs from breast cancer between January 2000 and December 2016 at 80 institutions.Median age at diagnosis of BMs was 56 years (22-90 years). About 47.8% (n = 732) of patients had HER2-positive, 21.4% (n = 328) had triple-negative and 30.8% (n = 471) had hormone receptor (HR)-positive, HER2-negative (luminal-like) primary tumours. The proportion of patients with HER2-positive BMs decreased comparing the years 2000-2009 with 2010-2015 (51%-44%), whereas the percenta…

Outcome Prediction in Node-Negative Breast Cancer Based on ASCO-Recommended Biomarkers uPA/PAI-1 Using the Final 10-Year Analysis of the Randomized Multicenter Chemo N0 Trial Compared to Adjuvant Online™.

Abstract Background: Based on interim analysis of Chemo N0, the first prospective multicenter randomized clinical trial using biomarkers uPA/PAI-1 for risk stratification and chemotherapy selection in N0 breast cancer, uPA/PAI-1 are now recommended for routine use by ASCO and AGO guidelines. Final 10-year follow-up of Chemo N0 has validated the clinically relevant long-term prognostic and predictive impact of uPA/PAI-1 in N0 breast cancer. To quantify the clinical utility of this impact, outcomes in subgroups defined by these biomarkers were compared to predictions of Adjuvant Online™, the leading validated tool based on established clinical factors. Methods: In Chemo N0, patients (n=647, 1…

Control of cellular phosphatidylinositol 4,5-bisphosphate levels by adhesion signals and Rho GTPases in NIH 3T3 fibroblasts

The involvement of small GTPases of the Rho family in the control of phosphoinositide metabolism by adhesion signals was examined in NIH 3T3 fibroblasts. Abrogation of adhesion signals by detachment of cells from their substratum resulted in a time-dependent decrease in the cellular level of PtdIns(4,5)P2 by approximately 50%. This effect could be mimicked by treatment of adherent cells with Clostridium difficile toxin B and toxin B-1470, which inhibit specific subsets of Rho and Ras GTPases. Detachment of cells that had been pretreated with the clostridial toxins did not cause a further reduction in PtdIns(4,5)P2 levels, suggesting that the target GTPases are integrated into the control of…

Multivariate independent prognostic factors in endometrial carcinoma: A clinicopathologic study in 181 patients

The aim of this study was to evaluate the biologic outcome of endometrial carcinomas as compared to clinical and pathologic parameters and to identify multivariate independent prognostic factors. Charts were abstracted from patients with endometrial carcinoma from 1985 to 1995. Data on clinicopathologic variables, adjuvant treatment, site of recurrence, and survival were collected. χ2 test was used to test association between variables. Kaplan-Maier method was used for survival analysis and Cox proportional hazards model for multiple regression analysis. Univariate analysis revealed that FIGO stage, tumor grade, depth of myometrial invasion, biochemical analysis of progesterone receptor sta…

Indikatoren schulischen Wohlbefindens bei gesunden und chronisch kranken Kindern: Psychometrische Prüfung und Validierung adaptierter FEESS-Skalen

Zusammenfassung. Das schulbezogene Wohlbefinden (SBWB) ist eine wichtige Voraussetzung für schulischen Erfolg. Trotzdem existieren – insbesondere mit Blick auf die Erfassung des SBWB von Erstklässlern – im deutschsprachigen Raum nur vereinzelt Studien. Dies lässt sich möglicherweise durch das Fehlen geeigneter Instrumente begründen. Dies gilt auch und insbesondere dann, wenn der Gesundheitszustand der Kinder berücksichtigt werden soll. Das Ziel der vorliegenden Arbeit besteht in der Validierung des adaptierten Fragebogens zur Erfassung von emotionalen und sozialen Schulerfahrungen (FEESS 1 – 2; Rauer & Schuck, 2004 ) mit Fokus auf die Eignung des Instruments für chronisch kranke und ge…

Quality of life and adjuvant tamoxifen treatment in breast cancer patients

About two-thirds of all breast cancer patients are treated with adjuvant hormonal therapy. Side effects of tamoxifen and their effects on physical, emotional and social functioning have been shown to impair the quality of life. Aim of this paper was to evaluate the side effects and level of influence on the physical, emotional and social functioning caused by tamoxifen treatment. For assessment of quality of life an own questionnaire was designed. Between January 2001 and December 2003, 136 women with breast cancer and adjuvant tamoxifen therapy were included in this study. Data of side effects, physical and mental health and patients' self-evaluation identified detrimental effects on patie…

Last glacial millennial-scale hydro-climate and temperature changes in Puerto Rico constrained by speleothem fluid inclusion δ<sup>18</sup>O and δ<sup>2</sup>H values

Abstract. We present speleothem fluid inclusion δ18Of and δ2Hf values from Larga Cave, Puerto Rico, that covers the interval between 46.2 to 15.3 ka before present on millennial scale, including the Last Glacial Maximum (LGM) and several stadial and interstadial cycles. The dataset can be divided in two main clusters of stable isotope compositions of the fluid inclusion water with respect to the global meteoric water line which coincide with strong variations in the water content of the stalagmite. In particular, this clustering is found to be climate related, where the first cluster comprises samples from cold and dry periods, such as Heinrich and Greenland stadials, as well as parts of th…

Non-Canonical WNT Signaling Regulates TGF-²1-Induced Extracellular Matrix Production By Airway Smooth Muscle Cells

Restoration of Clostridium difficile toxin-B-inhibited phospholipase D by phosphatidylinositol 4,5-bisphosphate.

Receptor signalling to phospholipase D (PLD) in human embryonic kidney (HEK) cells stably expressing the m3 muscarinic acetylcholine receptor apparently involves Rho proteins. Since phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] has been recognized as an essential cofactor for PLD activity and since activated Rho proteins have been reported to stimulate the synthesis of PtdIns(4,5)P2, we studied whether in HEK cells PLD activity is regulated by PtdIns(4,5)P2 and, in particular, whether PtdIns(4,5)P2 can restore PLD activity inhibited by Clostridium difficile toxin B, which inactivates Rho proteins. Addition of MgATP to permeabilized HEK cells increased basal PLD activity and potentia…

Efficacy and Safety of First-Line Bevacizumab (BEV) Combined with Paclitaxel (PAC) According to Age: Subpopulation Analysis of a Large, Multicenter, Non-Interventional Study in Patients (Pts) with HER2-Negative Metastatic Breast Cancer (MBC).

Abstract Background: In three randomized phase III trials (E2100, AVADO, RIBBON-1), the combination of Bev with taxane-based therapy significantly improved PFS and response rate versus taxane alone in HER2-negative MBC. Subpopulation analysis of AVADO suggested that the magnitude of the benefit derived from Bev was similar in older and younger pts (≥65 vs <65 years). To gain further information on the safety and efficacy of first-line Bev–pac in older pts treated in the real-life setting, we conducted a subpopulation analysis of data from an ongoing multicenter non-interventional study initiated after the approval of Bev in Germany. Materials and methods: Pts who had received no prio…

Abstract P1-13-01: Final results of the ASG1-3 study, a randomized phase III study comparing a standard dose chemotherapy with epirubicin/cyclophosphamide and paclitaxel with a dose dense regimen with epirubicin and paclitaxel

Abstract Background Dose dense chemotherapy (DDT) has shown improvements of disease-free survival (DFS) and overall survival for primary breast cancer patients with a high risk of relapse. There are much less data about the effect of DDT in patients with intermediate risk of recurrence (1-3 positive axillary lymph nodes). Aim of this prospectively randomized trial was to investigate the superiority of a DDT schedule over a standard chemotherapy (ST) in primary breast cancer patients with 1-3 positive axillary lymph nodes. Methods The ASG1-3 study is a prospectively randomized, open label phase III study of the Adjuvant Study Group of the NOGGO association. Patients were eligible for the tri…

Sorafenib in combination with docetaxel as first-line therapy for HER2-negative metastatic breast cancer: Final results of the randomized, double-blind, placebo-controlled phase II MADONNA study.

Abstract Background This multicenter, double-blind phase II study assessed the antitumor activity and toxicity profile of docetaxel with the antiangiogenic multikinase inhibitor sorafenib or matching placebo as a first-line treatment in patients with metastatic or locally advanced HER2-negative breast cancer. Patients and methods Patients were randomized 1:1 to receive docetaxel 100 mg/m2 on day 1 every 3 weeks in combination with sorafenib 400 mg bid or placebo on days 2–18 of each cycle until tumor progression, or unacceptable toxicity. Sorafenib/placebo could be continued at the investigator's discretion if docetaxel was stopped due to toxicity. Primary endpoint was progression free surv…

Multivariate independent prognostic factors in endometrial carcinoma: A clinicopathologic study in 181 patients: 10 years experience at the Department of Obstetrics and Gynecology of the Mainz University

The aim of this study was to evaluate the biologic outcome of endometrial carcinomas as compared to clinical and pathologic parameters and to identify multivariate independent prognostic factors. Charts were abstracted from patients with endometrial carcinoma from 1985 to 1995. Data on clinicopathologic variables, adjuvant treatment, site of recurrence, and survival were collected. chi2 test was used to test association between variables. Kaplan-Maier method was used for survival analysis and Cox proportional hazards model for multiple regression analysis. Univariate analysis revealed that FIGO stage, tumor grade, depth of myometrial invasion, biochemical analysis of progesterone receptor s…