97 results on '"Doris Augustin"'
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2. Supplementary Figure S3 from Impact of RNA Signatures on pCR and Survival after 12-Week Neoadjuvant Pertuzumab plus Trastuzumab with or without Paclitaxel in the WSG-ADAPT HER2+/HR− Trial
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Nadia Harbeck, Ulrike Nitz, Hans Heinrich Kreipe, Friedrich Feuerhake, Cornelia Kolberg-Liedtke, Hua Ni, Ronald Kates, Christine zu Eulenburg, Enrico Pelz, Hans Holger Fischer, Andrea Stefek, Toralf Reimer, Helmut Forstbauer, Claudia Schumacher, Katja Krauss, Rachel Wuerstlein, Jochem Potenberg, Michael Braun, Doris Augustin, Eva-Maria Grischke, Sherko Kuemmel, Jenci Palatty, Matthias Christgen, Daniel Ulbrich-Gebauer, Claudia Biehl, Oleg Gluz, and Monika Graeser
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Supplementary Figure 3 shows association between RNA signatures and overall survival
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- 2023
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3. Data from Impact of RNA Signatures on pCR and Survival after 12-Week Neoadjuvant Pertuzumab plus Trastuzumab with or without Paclitaxel in the WSG-ADAPT HER2+/HR− Trial
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Nadia Harbeck, Ulrike Nitz, Hans Heinrich Kreipe, Friedrich Feuerhake, Cornelia Kolberg-Liedtke, Hua Ni, Ronald Kates, Christine zu Eulenburg, Enrico Pelz, Hans Holger Fischer, Andrea Stefek, Toralf Reimer, Helmut Forstbauer, Claudia Schumacher, Katja Krauss, Rachel Wuerstlein, Jochem Potenberg, Michael Braun, Doris Augustin, Eva-Maria Grischke, Sherko Kuemmel, Jenci Palatty, Matthias Christgen, Daniel Ulbrich-Gebauer, Claudia Biehl, Oleg Gluz, and Monika Graeser
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Purpose:To identify associations of biological signatures and stromal tumor-infiltrating lymphocytes (sTIL) with pathological complete response (pCR; ypT0 ypN0) and survival in the Phase II WSG-ADAPT HER2+/HR− trial (NCT01817452).Experimental Design:Patients with cT1-cT4c, cN0–3 HER2+/HR− early breast cancer (EBC) were randomized to pertuzumab+trastuzumab (P+T, n = 92) or P+T+paclitaxel (n = 42). Gene expression signatures were analyzed in baseline biopsies using NanoString Breast Cancer 360 panel (n = 117); baseline and on-treatment (week 3) sTIL levels were available in 119 and 76 patients, respectively. Impacts of standardized gene expression signatures on pCR and invasive disease-free survival (iDFS) were estimated by logistic and Cox regression.Results:In all patients, ERBB2 [OR, 1.70; 95% confidence interval (CI), 1.08–2.67] and estrogen receptor (ER) signaling (OR, 1.72; 95% CI, 1.13–2.61) were favorable, whereas PTEN (OR, 0.57; 95% CI, 0.38–0.87) was unfavorable for pCR. After 60 months median follow-up, 13 invasive events occurred (P+T: n = 11, P+T+paclitaxel: n = 2), none following pCR. Gene signatures related to immune response (IR) and ER signaling were favorable for iDFS, all with similar HR about 0.43–0.55. These patterns were even more prominent in the neoadjuvant chemotherapy-free group, where additionally BRCAness signature was unfavorable (HR, 2.00; 95% CI, 1.04–3.84). IR signatures were strongly intercorrelated. sTILs (baseline/week 3/change) were not associated with pCR or iDFS, though baseline sTILs correlated positively with IR signatures.Conclusions:Distinct gene signatures were associated with pCR versus iDFS in HER2+/HR− EBC. The potential role of IR in preventing recurrence suggests that patients with upregulated IR signatures could be candidates for de-escalation concepts in HER2+ EBC.
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- 2023
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4. Adjuvant Docetaxel in Node-Negative Breast Cancer Patients: A Randomized Trial of AGO-Breast Study Group, German Breast Group, and EORTC-Pathobiology Group
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Christoph Thomssen, Martina Vetter, Eva J. Kantelhardt, Christoph Meisner, Marcus Schmidt, Pierre M. Martin, Florian Clatot, Doris Augustin, Volker Hanf, Daniela Paepke, Wolfgang Meinerz, Gerald Hoffmann, Wolfgang Wiest, Fred C. G. J. Sweep, Manfred Schmitt, Fritz Jänicke, Sibylle Loibl, Gunter von Minckwitz, and Nadia Harbeck
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adjuvant chemotherapy ,Cancer Research ,All institutes and research themes of the Radboud University Medical Center ,Oncology ,Article ,node-negative breast cancer ,uPA/PAI-1 ,docetaxel ,Women's cancers Radboud Institute for Health Sciences [Radboudumc 17] ,ddc - Abstract
Contains fulltext : 290914.pdf (Publisher’s version ) (Open Access) BACKGROUND: In node-negative breast cancer (NNBC), a high risk of recurrence is determined by clinico-pathological or tumor-biological assessment. Taxanes may improve adjuvant chemotherapy. METHODS: NNBC 3-Europe, the first randomized phase-3 trial in node-negative breast cancer (BC) with tumor-biological risk assessment, recruited 4146 node-negative breast cancer patients from 2002 to 2009 in 153 centers. Risk assessment was performed by clinico-pathological factors (43%) or biomarkers (uPA/PAI-1, urokinase-type plasminogen activator/its inhibitor PAI-1). High-risk patients received six courses 5-fluorouracil (500 mg/m(2)), epirubicin (100 mg/m(2)), cyclophosphamide (500 mg/m(2)) (FEC), or three courses FEC followed by three courses docetaxel 100 mg/m(2) (FEC-Doc). Primary endpoint was disease-free survival (DFS). RESULTS: In the intent-to-treat population, 1286 patients had received FEC-Doc, and 1255 received FEC. Median follow-up was 45 months. Tumor characteristics were equally distributed; 90.6% of tested tumors had high uPA/PAI-1-concentrations. Planned courses were given in 84.4% (FEC-Doc) and 91.5% (FEC). Five-year-DFS was 93.2% (95% C.I. 91.1-94.8) with FEC-Doc and 93.7% (91.7-95.3) with FEC. Five-year-overall survival was 97.0% (95.4-98.0) for FEC-Doc and 96.6% % (94.9-97.8) for FEC. CONCLUSIONS: With adequate adjuvant chemotherapy, even high-risk node-negative breast cancer patients have an excellent prognosis. Docetaxel did not further reduce the rate of early recurrences and led to significantly more treatment discontinuations.
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- 2023
5. ABC5 – Internationale Konsensuskonferenz zum fortgeschrittenen Mammakarzinom, Lissabon, 16.11.2019 – Deutsche Expertengruppe kommentiert ABC5-Abstimmungsergebnisse
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Renate Haidinger, Moritz Schwoerer, Hans-Joachim Lück, Isabel Radke, Diana Lüftner, Nadia Harbeck, Eugen Ruckhäberle, Christian M. Kurbacher, Peter A. Fasching, Christoph Thomssen, Volkmar Müller, Rachel Würstlein, Susanne Briest, Norbert Marschner, Lothar Müller, Johannes Ettl, Dieter Steinfeld-Birg, Katja Ziegler-Löhr, Michael Untch, F Förster, Eva Schumacher-Wulf, Doris Augustin, and Iris Scheffen
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03 medical and health sciences ,0302 clinical medicine ,business.industry ,030220 oncology & carcinogenesis ,Medicine ,030212 general & internal medicine ,business - Abstract
ZusammenfassungVom 14. bis 16. November 2019 fand in Lissabon die fünfte internationale Konsensuskonferenz ABC5 (Advanced Breast Cancer Fifth Consensus) zu Diagnostik und Behandlung des fortgeschrittenen Mammakarzinoms statt. Ziel ist es, die Behandlung der Patientinnen mit fortgeschrittenem Mammakarzinom weltweit auf evidenzbasierter Grundlage zu standardisieren und sicherzustellen, dass Patientinnen überall auf der Welt adäquat behandelt werden und Zugang zu neuen Therapien erhalten. Ein inhaltlicher Schwerpunkt lag dieses Jahr auf neuen Entwicklungen und Studienergebnissen beim fortgeschrittenen Mammakarzinom sowie der Präzisionsmedizin. Zudem ist die Zusammenarbeit mit den Patientenvertreterinnen aus aller Welt ein wichtiges Anliegen der ABC-Konferenz, weshalb in dem international zusammengesetzten ABC-Panel auch Patientenvertreterinnen sind. Im vorliegenden Manuskript werden die Abstimmungsergebnisse der ABC5-Panelisten vor Ort durch eine Arbeitsgruppe deutscher Brustkrebsexperten für den Therapiealltag in Deutschland kommentiert. Der Kommentierung liegen die Empfehlungen der Arbeitsgemeinschaft Gynäkologische Onkologie (AGO), Kommission „Mamma“, zugrunde. Sie erscheint sinnvoll, da in den ABC-Konsensus auch länderspezifische Besonderheiten einfließen.
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- 2020
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6. Differential impact of prognostic parameters in hormone receptor–positive lobular breast cancer
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Doris Augustin, Rachel Wuerstlein, Henriette Christgen, Toralf Reimer, Nadia Harbeck, Bahriye Aktas, Ronald E. Kates, Benno Nuding, Marianne Just, Petra Krabisch, Wolfram Malter, Oleg Gluz, Monika Graeser, Michael R. Clemens, Sherko Kuemmel, Andrea Stefek, Matthias Christgen, Frederick L. Baehner, Mieke Raap, Hans Kreipe, and Ulrike Nitz
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Adult ,Cancer Research ,medicine.medical_specialty ,Multivariate analysis ,Adolescent ,Breast Neoplasms ,Gastroenterology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,medicine ,Humans ,030212 general & internal medicine ,Lymph node ,Aged ,medicine.diagnostic_test ,business.industry ,Hazard ratio ,Middle Aged ,Progesterone Receptor Status ,Prognosis ,medicine.disease ,medicine.anatomical_structure ,Oncology ,Hormone receptor ,030220 oncology & carcinogenesis ,Biomarker (medicine) ,Female ,Oncotype DX ,business - Abstract
BACKGROUND Invasive lobular breast cancer (BC) is the second most common BC subtype. Prognostic parameters (tumor classification, lymph node status, histologic grade, Oncotype DX recurrence score [RS], progesterone receptor status, and Ki67 index) were retrospectively studied in a large, prospective clinical trial encompassing 2585 patients who had hormone receptor-positive early BC (the West German Study Group PlanB trial). METHODS BCs were centrally reviewed and classified as lobular (n = 353; 14%) or nonlobular (n = 2232; 86%). The median follow-up was 60 months. Five-year disease-free survival (DFS) estimates were obtained using the Kaplan-Meier method. Prognostic parameters were evaluated using Cox proportional hazard models. RESULTS Lobular BC was associated with higher tumor classification, higher lymph node status, lower histologic grade, lower Ki67 index, and low or intermediate RS. The prevalence of high RS (RS range, 26-100) was 3-fold lower in patients who had lobular BC compared with those who had nonlobular BC (8% vs 24%; P
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- 2020
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7. ABC5 International Consensus Conference on Advanced Breast Cancer, Lisbon, 16 November 2019
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Susanne Briest, Doris Augustin, Isabel Radke, Eugen Ruckhäberle, Eva Schumacher-Wulf, Michael Untch, Hans-Joachim Lück, Johannes Ettl, Lothar Müller, Renate Haidinger, Peter A. Fasching, F Förster, Diana Lüftner, Rachel Würstlein, Moritz Schwoerer, Christian M. Kurbacher, Volkmar Müller, Katja Ziegler-Löhr, Christoph Thomssen, Dieter Steinfeld-Birg, Nadia Harbeck, Norbert Marschner, and Iris Scheffen
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medicine.medical_specialty ,precision medicine ,media_common.quotation_subject ,Advanced breast ,ABC5-Konsensus ,Commission ,Disease ,German ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Voting ,Maternity and Midwifery ,Review/Übersicht ,Medicine ,GebFra Science ,skin and connective tissue diseases ,media_common ,advanced breast cancer ,030219 obstetrics & reproductive medicine ,Präzisionsmedizin ,business.industry ,ABC5 consensus ,Obstetrics and Gynecology ,Cancer ,2019 study data ,Precision medicine ,medicine.disease ,language.human_language ,Family medicine ,Studiendaten 2019 ,fortgeschrittenes Mammakarzinom ,language ,business - Abstract
The Advanced Breast Cancer Fifth International Consensus Conference (ABC5) which focuses on the diagnosis and treatment of advanced breast cancer was held in Lisbon on November 14 – 16, 2019. The aim of the conference is to standardize the treatment of advanced breast cancer worldwide using evidence-based data and to ensure that patients with advanced breast disease anywhere in the world are treated appropriately and have access to the latest therapies. This year, the emphasis was on new developments and study results from patients with advanced breast cancer as well as precision medicine. The collaboration with patient advocates from all over the globe is also an important goal of the ABC Conference, which is why the international ABC panel also included a number of patient advocates. We present a commentary on the voting results of the ABC5 panelists in Lisbon by a working group of German breast cancer specialists together with the implications for routine clinical care in Germany. The commentary is based on the recommendations of the Breast Commission of the German Gynecological Oncology Working Group (AGO). This commentary is useful, it includes country-specific features for the ABC consensus.
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- 2020
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8. Protroca: A Noninterventional Study on Prophylactic Lipegfilgrastim against Chemotherapy-Induced Neutropenia in Nonselected Breast Cancer Patients
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Oliver J. Stoetzer, Doris Augustin, Kerstin Lüdtke-Heckenkamp, Nadia Harbeck, J. Tio, Ulrike Nitz, Petra Krabisch, Andrea Grafe, Andrea Stefek, Monika Graeser, Ronald E. Kates, Rachel Wuerstlein, Oleg Gluz, D Forstmeyer, Iris Schrader, Helmut Forstbauer, Eva-Maria Grischke, Gabriele Kaltenecker, and Raquel von Schumann
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Chemotherapy ,medicine.medical_specialty ,business.industry ,medicine.medical_treatment ,Cancer ,Neutropenia ,medicine.disease ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Oncology ,Chemotherapy induced ,030220 oncology & carcinogenesis ,Internal medicine ,Medicine ,Surgery ,030212 general & internal medicine ,business ,Adverse effect ,Lipegfilgrastim ,Febrile neutropenia ,Research Article - Abstract
Background: Protroca evaluated the efficacy and safety of primary and secondary prophylaxis of neutropenia with lipegfilgrastim (Lonquex®) in breast cancer patients receiving neoadjuvant or adjuvant chemotherapy (CT). Patients and Methods: Of the 255 patients enrolled, 248 patients were evaluable for the intent-to-treat (ITT) and 194 patients for the per-protocol set. Primary and secondary end points after lipegfilgrastim treatment were assessed. Results: Nine patients of the ITT set receiving lipegfilgrastim as primary prophylaxis (n = 222) had febrile neutropenia of grade 3–4 (5 patients) or infection of grade 3–4 (4 patients); 1/26 of those receiving secondary prophylaxis had an event. Dose reductions were performed in 9.5% of the patients. Postponement of cancer CT cycles for >3 days occurred in Conclusions: Application of lipegfilgrastim was effective as primary and secondary prophylaxis in the prevention of CT-induced neutropenia in breast cancer.
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- 2020
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9. Abstract P4-17-06: Treatment strategies in male breast cancer: Results of a prospective multicenter study
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Mattea Reinisch, C Brucker, Marc Thill, Felix Flock, Michael G. Schrauder, Atanas Ignatov, Serban-Dan Costa, Holm Eggemann, Doris Augustin, Susanne Kraudelt, Uta Ringsdorf, Anke Kleine-Tebbe, Gabriele Gad, and Susen Schirrmeister
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Cancer Research ,medicine.medical_specialty ,Axillary lymph nodes ,business.industry ,medicine.medical_treatment ,Cancer ,medicine.disease ,medicine.anatomical_structure ,Breast cancer ,Oncology ,Internal medicine ,Male breast cancer ,Breast-conserving surgery ,medicine ,Prospective cohort study ,business ,Radical mastectomy ,Febrile neutropenia - Abstract
Background. In this prospective analysis, we aimed to characterize the treatment opinions on male breast cancer (MBC). Patients and methods. In this prospective cohort study we included patients treated between May2009 and June 2018 for MBC. Results. The median follow-up was 30 months (range 2-84 months) and the median age at diagnosis was 69 years (range 27-96 years). Radical mastectomy was performed in 354 (96.2%) cases. Most (n=194, 52.9%) patients underwent sentinel-node biopsy (SNB). However, the vast majority of patients with clinical and sonographic suspicious axillary lymph nodes (n=72, 81.8%) underwent ALND. Adjuvant radiation of chest wall post mastectomy or of the breast post breast conserving surgery was performed in 193 (51.9%) patients. Systemic therapy was administered to 155 (41.0%) patients, and was administered predominantly in the adjuvant setting. Most common was anthracycline-taxane-based therapy. Of patients with HER2 (n=43) overexpressing tumors, 29 (67.4%) received trastuzumab. Adjuvant endocrine therapy was administered to 92.3% of patients, predominantly tamoxifen. Important decision criteria for adjuvant radiation and chemotherapy were advanced stage of disease, lymph node metastases, undifferentiated tumors, lymph- and blood vessel invasion. During the follow up period 609 cycles of chemotherapy were administered (median 6 cycles per person). Haematological and non-haematological toxic effects were observed in 68 (16.4%) and 57 (53.3%) patients, respectively. Grade 3 and 4 haematological events were rare. The most common was neutropenia in 17 (15.8%) and febrile neutropenia in 10 (9.3%) cases. Nausea and vomiting were the most commonly observed grade 3 and 4 non-haematological adverse events observed in 7 (4.6%) cases. Endocrine therapy was discontinued in 53 (16.2%) patients and chemotherapy in 25 (16.1%) cases. Conclusions. In this large prospective study, we found that MBC is treated according to current guidelines and treatment seems to be not inferior in comparison with that treatment of FBC. Citation Format: Holm Eggemann, Cosima Brucker, Susen Schirrmeister, Uta Ringsdorf, Doris Augustin, Michael Schrauder, Marc Thill, Felix Flock, Susanne Kraudelt, Gabriele Gad, Anke Kleine-Tebbe, Mattea Reinisch, Serban- Dan Costa, Atanas Ignatov. Treatment strategies in male breast cancer: Results of a prospective multicenter study [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-17-06.
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- 2020
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10. Abstract P4-10-05: Predictive value of HER2 expression, early response and tumor infiltrating lymphocytes (TILs) on efficacy of de-escalated pertuzumab+trastuzumab in the neoadjuvant WSG-ADAPT-HER2+/HR- trial
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Oleg Gluz, Cornelia Kolberg-Liedtke, Claudia Biehl, Matthias Christgen, Sherko Kuemmel, Eva-Maria Grischke, Doris Augustin, Michael Braun, Jochem Potenberg, Monika Graeser, Ronald Kates, Rachel Wuerstlein, Friedrich Feuerhake, Ulrike Nitz, Hans Kreipe, Nadia Harbeck, and West German Study Group
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Oncology ,Cancer Research ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Tumor-infiltrating lymphocytes ,medicine.medical_treatment ,Population ,Cancer ,medicine.disease ,Lapatinib ,Breast cancer ,Trastuzumab ,Internal medicine ,medicine ,Pertuzumab ,skin and connective tissue diseases ,business ,education ,Neoadjuvant therapy ,medicine.drug - Abstract
Purpose: Only limited data are available on predictive markers for use of chemotherapy-free, anti-HER2 combinations in HER2-positive early breast cancer (eBC), in particular within the molecularly distinct HER2+/HR- subgroup. Background: In the ADAPT HER2+/HR- trial, a promising pCR of about 43-45% was found in patients treated by 4 cycles of pertuzumab and trastuzumab with either defined early response (low tumor cellularity or relative Ki-67 decrease ≥30%) or indeterminate early response (e.g. no visible tumor by ultrasound), compared to under 10% in early non-responders. In addition to early response, HER2 protein expression and stromal TIL (s-TIL) dynamics after one cycle of therapy are promising tools for identification of patients with high likelihood of pathological complete response (pCR) after therapy with double anti-HER2 blockade (e.g. by lapatinib+trastuzumab) or T-DM1. Methods: Patients with cT1-cT4c, cN0-3 early HER2+/HR- BC (n=134) were treated with 4 cycles of P+T +/- paclitaxel d1,8,15 q3w. Primary endpoint of the study was pCR (ypT0/is, ypN0). All tumors were HR-negative (ER and PR Tumors were classified as “HER2-low” if HER2-1+ or HER2-2+ by either local or central IHC assessment, otherwise “HER2-high”. s-TILs were measured semi-quantitively according to current international consensus in triplicate at baseline and on-treatment (at cycle 2); the median of the three measurements was taken to define the quantities TIL-0 and TIL-3, respectively. “Lymphocyte-dominant subtype” at baseline and cycle 2 were defined as TIL-0≥40% and TIL-3≥40%, respectively. The present analysis characterizes the predictive impact of early response HER2 protein expression, and s-TILs on pCR under dual anti-HER2 therapy for the first time within a prospective neoadjuvant trial specific to the HER2+/HR- BC subtype. Results: As previously reported, pCR was 34.4% without chemotherapy and 90.5% with chemotherapy. TIL-0 and TIL-3 were available in n=119/134 and n=103/134 patients, respectively. TIL-0 and TIL-3 were not significantly associated with pCR in the whole cohort or within the T+P arm, either modeled as a continuous variable or in terms of binary variables representing lymphocyte-dominant subtype or defined by the respective population medians. HER2-high expression was found in 87% of patients. In the T+P arm, pCR was much higher in HER2-high than HER2-low patients (40.3% vs. 0%, p=.003). In the T+P arm, 24 and 38 of 92 patients were classified as non- and responders, unclassified early response was observed in 30 of 92 patients. pCR in these groups were 8.3% vs. 44.7% vs. 42.9% respectively. Higher baseline TILs were positively associated with early response. Clinically meaningful pCR of 49% after only 4 cycles of chemotherapy-free P+T was seen in those patients with early response after one cycle of therapy and HER2-high classification, compared to 11.8% in the HER2-high/non-responder group). Conclusions: At present, a combination of baseline high HER2 expression with low cellularity after one cycle of neoadjuvant therapy – rather than s-TIL determination (at baseline or in response to therapy) – appears to be a simple and feasible tool for identification of candidates for de-escalated treatment in HER2+/HR- disease. Further research on high-precision determination of HER2-high expression (by immunohistochemistry vs. mRNA-based tools) is strongly needed for optimal patient selection for future chemotherapy de-escalation trials. Citation Format: Oleg Gluz, Cornelia Kolberg-Liedtke, Claudia Biehl, Matthias Christgen, Sherko Kuemmel, Eva-Maria Grischke, Doris Augustin, Michael Braun, Jochem Potenberg, Monika Graeser, Ronald Kates, Rachel Wuerstlein, Friedrich Feuerhake, Ulrike Nitz, Hans Kreipe, Nadia Harbeck, West German Study Group. Predictive value of HER2 expression, early response and tumor infiltrating lymphocytes (TILs) on efficacy of de-escalated pertuzumab+trastuzumab in the neoadjuvant WSG-ADAPT-HER2+/HR- trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-10-05.
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- 2020
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11. Immune markers and tumor-related processes predict neoadjuvant therapy response in the wsg-adapt her2-positive/hormone receptor-positive trial in early breast cancer
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Rachel Wuerstlein, Doris Augustin, Wolfram Malter, Michael Braun, Regula Deurloo, Cornelia Liedtke, O Gluz, Eva-Maria Grischke, Bahriye Aktas, Raquel von Schumann, Ronald E. Kates, S. Kuemmel, Sanne de Haas, Claudia Biehl, Helmut Forstbauer, Nadia Harbeck, J. Tio, Jochem Potenberg, Hans Kreipe, and Claudia Schumacher
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Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Medizin ,biomarkers ,breast cancer ,HER2-positive ,hormone receptor-positive ,immune markers ,Article ,Breast cancer ,Immune system ,Internal medicine ,medicine ,ddc:610 ,skin and connective tissue diseases ,Pathological ,neoplasms ,RC254-282 ,Neoadjuvant therapy ,business.industry ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Apoptosis ,Hormone receptor ,business ,CD8 ,Hormone - Abstract
Simple Summary Patients with “HER2-positive” early breast cancer are treated with antibodies to the HER2 protein along with chemotherapy, regardless of whether their cancer also has hormone receptors, or of its molecular features. Because patients with HER2-positive/hormone receptor-positive disease tend to live longer than those with HER2-positive/hormone receptor-negative disease, there may be some patients who are being overtreated under current guidelines. The aim of our exploratory translational analysis of the ADAPT HER2-positive/hormone receptor-positive trial was to investigate the potential of several prognostic (outcome regardless of therapy) and predictive (effect of therapy) biomarkers as early predictors of response to treatment before surgery. Comparison of these biomarkers before and after one treatment cycle, and their effects on whether patients’ cancers were completely removed at surgery, suggest that certain patients (those with treatment-induced CD8 protein-expressing cells infiltrating the cancer; without PIK3CA mutation; those with HER2-enriched tumors) may be candidates for less intensive treatment following pre-surgical therapy. Abstract Prognostic or predictive biomarkers in HER2-positive early breast cancer (EBC) may inform treatment optimization. The ADAPT HER2-positive/hormone receptor-positive phase II trial (NCT01779206) demonstrated pathological complete response (pCR) rates of ~40% following de-escalated treatment with 12 weeks neoadjuvant ado-trastuzumab emtansine (T-DM1) ± endocrine therapy. In this exploratory analysis, we evaluated potential early predictors of response to neoadjuvant therapy. The effects of PIK3CA mutations and immune (CD8 and PD-L1) and apoptotic markers (BCL2 and MCL1) on pCR rates were assessed, along with intrinsic BC subtypes. Immune response and pCR were lower in PIK3CA-mutated tumors compared with wildtype. Increased BCL2 at baseline in all patients and at Cycle 2 in the T-DM1 arms was associated with lower pCR. In the T-DM1 arms only, the HER2-enriched subtype was associated with increased pCR rate (54% vs. 28%). These findings support further prospective pCR-driven de-escalation studies in patients with HER2-positive EBC.
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- 2021
12. 4. Internationale Konsensuskonferenz zum fortgeschrittenen Mammakarzinom (ABC4), Lissabon, 04.11.2017
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Eugen Ruckhäberle, Christoph Thomssen, Rachel Würstlein, Diana Lüftner, Doris Augustin, Susanne Briest, Renate Haidinger, Michael Untch, Volkmar Müller, Johannes Ettl, Norbert Marschner, Nadia Harbeck, and Lothar Müller
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Gynecology ,medicine.medical_specialty ,CNS metastasis ,Political science ,medicine - Abstract
ZusammenfassungVom 2. bis 4. November 2017 fand in Lissabon unter Leitung von Frau Professor Fatima Cardoso die 4. Internationale Konsensuskonferenz ABC4 (Advanced Breast Cancer Forth Consensus) zu Diagnostik und Behandlung des fortgeschrittenen Mammakarzinoms (ABC) statt. Zur Vereinfachung wird im weiteren Text von ABC gesprochen, was im klinischen Alltag der metastasierten Brustkrebserkrankung oder der lokal weit fortgeschrittenen Erkrankung entspricht. Der inhaltliche Schwerpunkt lag dieses Jahr auf neuen Entwicklungen in der Behandlung des ABC. Diskutiert wurden unter anderem der Stellenwert der CDK4/6-Inhibition beim hormonrezeptor(HR-)positiven ABC, die duale Antikörperblockade beim HER2-positiven ABC, die PARP-Inhibition beim BRC-Amutierten tripel-negativen und luminalen ABC sowie potenzielle therapeutische Konsequenzen. Ein weiterer Fokus lag auf dem BRCA-assoziierten Mammakarzinom, der Behandlung von Hirnmetastasen sowie der individualisierten Therapieentscheidung auf der Grundlage einer molekularen Testung (sog. Präzisionsmedizin). Wie schon in den vergangenen Jahren ist die Zusammenarbeit mit den Vertretern von Patientenorganisationen aus aller Welt ein wichtiges Anliegen der ABC-Konferenz. Sie wurde auf der ABC4-Konferenz weiter intensiviert. Im Anschluss an die Konsensuskonferenz wurde die „Global Alliance“ gegründet mit dem Ziel, die erforderlichen Maßnahmen aus Sicht der Patientenvertreterinnen weltweit zu propagieren und zu koordinieren. In den ABC-Konsensus fließen aufgrund des international zusammengesetzten Expertenpanels zwangsläufig länderspezifische Besonderheiten ein. Wie schon in den vergangenen Jahren hat daher eine Arbeitsgruppe deutscher Brustkrebsexperten, die die Konsensusabstimmung der ABC-Panelisten vor Ort mitverfolgt und intensiv diskutiert haben, diese unter Berücksichtigung der deutschen Leitlinien zu Diagnostik und Therapie des Mammakarzinoms 1 2 für den Therapiealltag in Deutschland kommentiert. Die Abstimmungsergebnisse der ABC-Panelisten in Lissabon sind die Grundlage des ABC-Konsensus.
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- 2018
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13. 4th International Consensus Conference on Advanced Breast Cancer (ABC4), Lisbon, November 4, 2017
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Johannes Ettl, Diana Lüftner, Eugen Ruckhäberle, Volkmar Müller, Lothar Müller, Nadia Harbeck, Rachel Würstlein, Michael Untch, Norbert Marschner, Doris Augustin, Susanne Briest, Christoph Thomssen, and Renate Haidinger
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medicine.medical_specialty ,business.industry ,Obstetrics and Gynecology ,Cancer ,Context (language use) ,medicine.disease ,Precision medicine ,Metastatic breast cancer ,language.human_language ,German ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Alliance ,030220 oncology & carcinogenesis ,Family medicine ,Political science ,Maternity and Midwifery ,medicine ,language ,030212 general & internal medicine ,Personalized medicine ,business - Abstract
The fourth international advanced breast cancer consensus conference (ABC4) on the diagnosis and treatment of advanced breast cancer (ABC) headed by Professor Fatima Cardoso was once again held in Lisbon on November 2 – 4, 2017. To simplify matters, the abbreviation ABC will be used hereinafter in the text. In clinical practice, the abbreviation corresponds to metastatic breast cancer or locally far-advanced disease. This year the focus was on new developments in the treatment of ABC. Topics discussed included the importance of CDK4/6 inhibition in hormone receptor (HR)-positive ABC, the use of dual antibody blockade to treat HER2-positive ABC, PARP inhibition in triple-negative ABC and the potential therapeutic outcomes. Another major area discussed at the conference was BRCA-associated breast cancer, the treatment of cerebral metastasis, and individualized treatment decisions based on molecular testing (so-called precision medicine). As in previous years, close cooperation with representatives from patient organizations from around the world is an important aspect of the ABC conference. This cooperation was reinforced and expanded at the ABC4 conference. A global alliance was founded at the conclusion of the consensus conference, which aims to promote and coordinate the measures considered necessary by patient advocates worldwide. Because the panel of experts was composed of specialists from all over the world, it was inevitable that the ABC consensus also reflected country-specific features. As in previous years, a team of German breast cancer specialists who closely followed the consensus voting of the ABC panelists in Lisbon and intensively discussed the votes has therefore commented on the consensus in the context of the current German guidelines on the diagnosis and treatment of breast cancer 1, 2 used in clinical practice in Germany. The ABC consensus is based on the votes of the ABC panelists in Lisbon.
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- 2018
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14. Abstract P1-06-06: No age-related outcome disparities according to 21-gene recurrence score groups in early breast cancer patients treated by adjuvant chemotherapy in the prospective WSG PlanB trial
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Matthias Christgen, Toralf Reimer, H.H. Kreipe, A Pollmanns, A. Stefek, Rachel Wuerstlein, O Gluz, C Chao, Benno Nuding, S Shak, Michael R. Clemens, Wolfram Malter, U. Nitz, Doris Augustin, R Kates, Nadia Harbeck, F Lorenz-Salehi, and Christoph Uleer
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Oncology ,Cancer Research ,medicine.medical_specialty ,Chemotherapy ,Adjuvant chemotherapy ,business.industry ,medicine.medical_treatment ,Cancer ,medicine.disease ,Clinical trial ,Breast cancer ,Internal medicine ,medicine ,21 gene recurrence score ,business ,Adjuvant ,Early breast cancer - Abstract
Background: Elderly breast cancer (BC) patients (pts) have been reported to have worse BC-related outcome than younger pts, even within clinical trials such as TEAM. Shak et al. recently showed in a large SEER data analysis that in the high 21-gene recurrence score (RS) group, older pts (>70y) receive less chemotherapy (CT) and have a worse BC-specific mortality than younger pts. Here, we therefore aimed to see whether there are age-related outcome disparities according to RS groups in pts receiving state-of-the-art CT in the prospective WSG PlanB trial. Material and Methods: PlanB compared 6 cycles of anthracycline-free TC vs. standard anthracycline-taxane based CT (4xECà4xDoc) in patients with high risk pN0 (T2-4, G2-3, Results: In all pts with luminal cancer and RS results (n=2577), there was an age-related significant difference in RS risk group assignment (p25; in pts 40-69 years, 18.3% had RS≤11, 61% RS 12-25, and 20.7%% RS>25; in elderly pts (>70y), 19.5% had RS≤11, 55.3% RS 12-25, and 25.2% RS>25. Among patients receiving chemotherapy, RS>25 vs. RS25, there were no significant differences in DFS between any two of these three age groups. Conclusion: A substantial percentage of elderly patients (> 70y) presents with high-risk luminal disease; these patients are candidates for CT. In PlanB, about 25% of elderly luminal BC patients had high-risk (RS>25) tumors. Nevertheless, after receiving modern adjuvant CT, their DFS was comparable to that of non-elderly pts with high-risk RS tumors. Consequently, older BC pts with high-risk luminal tumors who are fit enough to receive adjuvant CT should be treated according to guidelines in order to overcome age-dependent survival disparities which have been observed in registries for high-RS tumors. Citation Format: Harbeck N, Gluz O, Wuerstlein R, Clemens M, Malter W, Reimer T, Nuding B, Stefek A, Pollmanns A, Augustin D, Uleer C, Lorenz-Salehi F, Shak S, Chao C, Christgen M, Kates R, Kreipe H, Nitz U. No age-related outcome disparities according to 21-gene recurrence score groups in early breast cancer patients treated by adjuvant chemotherapy in the prospective WSG PlanB trial [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-06-06.
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- 2018
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15. De-escalation strategies in HER2-positive early breast cancer (EBC): final analysis of the WSG-ADAPT HER2+/HR− phase II trial: efficacy, safety, and predictive markers for 12 weeks of neoadjuvant dual blockade with trastuzumab and pertuzumab ± weekly paclitaxel
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A. Kohls, Hans-Peter Fischer, Ronald E. Kates, Matthias Christgen, Michael Braun, T. Reimer, Hans Heinrich Kreipe, Nadia Harbeck, Jochem Potenberg, Katja Krauss, E-M. Grischke, Andrea Stefek, Helmut Forstbauer, O Gluz, Doris Augustin, Ulrike Nitz, Claudia Schumacher, Johannes Schumacher, Cornelia Liedtke, Sherko Kuemmel, and Rachel Wuerstlein
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Adult ,0301 basic medicine ,medicine.medical_specialty ,Adolescent ,Paclitaxel ,Receptor, ErbB-2 ,medicine.medical_treatment ,Medizin ,Phases of clinical research ,Breast Neoplasms ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Trastuzumab ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,medicine ,Humans ,Prospective Studies ,Survival rate ,Neoadjuvant therapy ,Aged ,Aged, 80 and over ,Taxane ,business.industry ,Hematology ,Middle Aged ,Prognosis ,Chemotherapy regimen ,Neoadjuvant Therapy ,Blockade ,Survival Rate ,030104 developmental biology ,Receptors, Estrogen ,Oncology ,030220 oncology & carcinogenesis ,Female ,Pertuzumab ,Receptors, Progesterone ,business ,Follow-Up Studies ,medicine.drug - Abstract
Response rates in HER2-overexpressing EBC treated with neoadjuvant chemotherapy and trastuzumab (T) have been improved by addition of pertuzumab (P). The prospective, phase II, neoadjuvant WSG-ADAPT HER2+/HR- trial assessed whether patients with strong early response to dual blockade alone might achieve pathological complete response (pCR) comparable to that of patients receiving dual blockade and chemotherapy. Female patients with HER2+/HR- EBC (M0) were randomized (5:2) to 12 weeks of T + P +/- weekly paclitaxel (pac) at 80 mg/m(2). Early response was defined as proliferation decrease a parts per thousand 30% of Ki-67 (versus baseline) or low cellularity (< 500 invasive tumor cells) in the 3-week biopsy. The trial was designed to test non-inferiority for pCR in early responding patients of the T + P arm versus all chemotherapy-treated patients. From February 2014 to December 2015, 160 patients were screened, 92 were randomized to T + P and 42 to T + P+pac. Baseline characteristics were well balanced (median age 54 versus 51.5 years, cT2 51.1 versus 52.4%, cN0 54.3 versus 61.9%);91.3% of patients completed T + P per protocol and 92.9% T + P+pac. The pCR rate in the T + P+pac arm was 90.5%, compared with 36.3% in the T + P arm as a whole. In the T + P arm, 24/92 were classified as non-responders, and their pCR rate was only 8.3% compared with 44.7% in responders (38/92) and 42.9% in patients with unclassified early response (30/92). No new safety signals were observed in the study population. Addition of taxane monotherapy to dual HER2 blockade in a 12-week neoadjuvant setting substantially increases pCR rates in HER2+/HR- EBC compared with dual blockade alone, even within early responders to dual blockade. Early non-response under dual blockade strongly predicts failure to achieve pCR.
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- 2017
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16. Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients: five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial
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Rachel Wuerstlein, Doris Augustin, Bahriye Aktas, Ronald E. Kates, F Lorenz-Salehi, Petra Krabisch, Benno Nuding, Wolfram Malter, Nadia Harbeck, Ulrike Nitz, Michael R. Clemens, Hans Kreipe, Marianne Just, Oleg Gluz, Toralf Reimer, Andrea Stefek, Calvin Chao, Matthias Christgen, Cornelia Liedtke, Sherko Kuemmel, and Steven Shak
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Medizin ,Disease ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,medicine ,Clinical endpoint ,Chemotherapy ,biology ,medicine.diagnostic_test ,business.industry ,medicine.disease ,030104 developmental biology ,030220 oncology & carcinogenesis ,Ki-67 ,biology.protein ,Personalized medicine ,business ,Oncotype DX ,Adjuvant - Abstract
The prospective phase 3 PlanB trial used the Oncotype DX® Recurrence Score® (RS) to define a genomically low-risk subset of clinically high-risk pN0-1 early breast cancer (EBC) patients for treatment with adjuvant endocrine therapy (ET) alone. Here, we report five-year data evaluating the prognostic value of RS, Ki-67, and other traditional clinicopathological parameters. A central tumour bank was prospectively established within PlanB. Following an early amendment, hormone receptor (HR)+ , pN0-1 RS ≤ 11 patients were recommended to omit chemotherapy. Patients with RS ≥ 12, pN2-3, or HR-negative/HER2-negative disease were randomised to anthracycline-containing or anthracycline-free chemotherapy. Primary endpoint: disease-free survival (DFS). PlanB Clinicaltrials.gov identifier: NCT01049425. From 2009 to 2011, PlanB enrolled 3198 patients (central tumour bank, n = 3073) with the median age of 56 years, 41.1% pN+, and 32.5% grade 3 EBC. Chemotherapy was omitted in 348/404 (86.1%) eligible RS ≤ 11 patients. After 55 months of median follow-up, five-year DFS in ET-treated RS ≤ 11 patients was 94% (in both pN0 and pN1) versus 94% (RS 12–25) and 84% (RS > 25) in chemotherapy-treated patients (p 2 cm, and RS, but not IHC4 or Ki-67 were independent adverse factors. If RS was excluded, IHC4 or both Ki-67 and PR entered the model. The impact of RS was particularly pronounced in patients with intermediate Ki-67 (>10%
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- 2017
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17. The Impact of Age on Quality of Life in Breast Cancer Patients Receiving Adjuvant Chemotherapy: A Comparative Analysis From the Prospective Multicenter Randomized ADEBAR trial
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Wolfgang Janni, Nadia Harbeck, Brigitte Rack, Marion Kiechle, Lukas Schwentner, Elena Leinert, Tobias Weissenbacher, Visnja Fink, A Wischnik, Martin Eichler, Doris Augustin, Susanne Singer, and Johannes Ettl
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Oncology ,Cancer Research ,Docetaxel ,0302 clinical medicine ,Quality of life ,Surveys and Questionnaires ,Antineoplastic Combined Chemotherapy Protocols ,Multicenter Studies as Topic ,Anthracyclines ,Longitudinal Studies ,Prospective Studies ,030212 general & internal medicine ,Young adult ,Prospective cohort study ,Antibiotics, Antineoplastic ,Age Factors ,Middle Aged ,humanities ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Practice Guidelines as Topic ,Female ,Taxoids ,Fluorouracil ,medicine.drug ,Epirubicin ,Adult ,Bridged-Ring Compounds ,medicine.medical_specialty ,Adolescent ,Cyclophosphamide ,Breast Neoplasms ,Young Adult ,03 medical and health sciences ,Breast cancer ,Internal medicine ,medicine ,Humans ,Aged ,business.industry ,Cancer ,medicine.disease ,Clinical Trials, Phase III as Topic ,Quality of Life ,Patient Compliance ,business - Abstract
Elderly breast cancer patients are affected by poorer quality of life (QoL) compared to younger patients. Because QoL has a relevant impact on guideline-adherent treatment, elderly breast cancer patients are often undertreated, especially with regard to adjuvant chemotherapy, and overall survival is decreased. Thus, understanding the impact of chemotherapy on QoL in elderly patients is crucial. This study compared QoL in patients aged 65 years and 65 to 70 years receiving adjuvant chemotherapy as a secondary outcome in the prospective randomized multicenter ADEBAR trial.Patients with lymph node-positive breast cancer were prospectively randomized for either sequential anthracycline-taxane or epirubicin/fluorouracil/cyclophosphamid chemotherapy (FEC) therapy. QoL was assessed at baseline (t1), before cycle 4 FEC, and cycle 5 epirubicin/cyclophosphamid-docetaxel (EC-DOC) (t2), 4 weeks after chemotherapy (t3), and 6 weeks after radiation (t4) using the European Organization for Research and Treatment for Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30) and the Breast Cancer-Specific Module (QLQ-BR23). We compared patients aged 65 years and 65 to 70 years with respect to QoL and discontinuation of chemotherapy.A total of 1363 patients were enrolled onto the ADEBAR trial, with 16.7% of the patients aged 65 to 70 years. In elderly patients, Eastern Cooperative Oncology Group performance status was higher and global health status and physical functioning were lower at baseline. Global health status decreased between t1 and t3 by 7 points in patients 65 years and by 11 points in patients 65 to 70 years, and physical functioning decreased in the same period by 13.4 points in patients aged 65 years and by 15.9 points in patients 65 to 70 years. In both groups, at t4 global health status exceeded baseline by 6 points, and physical functioning was 1.3 points under baseline in patients 65 years old and 3 points under baseline in patients 65 to 70 years. There was a trend to more fatigue in elderly patients and to more nausea and vomiting while receiving chemotherapy in younger patients at t3. There was a higher dropout rate in patients aged 65 to 70 years (25.7%) than in patients aged 65 years (16.2%).There were only small or trivial differences in QoL in patients aged 65 years versus 65 to 70 years who were receiving adjuvant chemotherapy, although the dropout rate from chemotherapy was notably higher in elderly breast cancer patients.
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- 2017
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18. Abstract P1-09-05: The role of immune and apoptosis markers for prediction of pCR in the WSG-ADAPT HER2+/HR+ phase II trial evaluating 12-weeks of neoadjuvant TDM1 ± endocrine therapy (ET) versus T + ET in HER2-positive hormone-receptor-positive early breast cancer (EBC)
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J. Potenberg, R Kates, C Matthias, H.H. Kreipe, Stefan Kraemer, Anke Kleine-Tebbe, Bahriye Aktas, Doris Augustin, Rachel Wuerstlein, S Kümmel, Claudia Schumacher, O Gluz, Michael Braun, Nadia Harbeck, J. Tio, Helmut Forstbauer, U. Nitz, SL de Haas, Cornelia Liedtke, Regula Deurloo, E-M Grischke, and Johannes Schumacher
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Pathology ,business.industry ,Endocrine therapy ,03 medical and health sciences ,030104 developmental biology ,Immune system ,Apoptosis ,Hormone receptor ,Internal medicine ,medicine ,business ,Early breast cancer - Abstract
Background: Immune and apoptosis biomarkers are potential prognostic/predictive markers in HER2+ EBC. High PD-L1 expression was shown to be predictive for lower pCR after chemotherapy+trastuzumab+/-pertuzumab, particularly in HER2+, ER- disease. Yet, HER2+ EBC co-expressing hormone receptors is a distinct entity. The ADAPT HER2+/HR+ phase II trial (n=376) compared 12 weeks of neoadjuvant T-DM1 + ET vs. trastuzumab (T)+ET and demonstrated pCR rates of about 41% in both (well tolerated) T-DM1 arms. Methods: In order to identify potential early predictors for pCR (i.e. no invasive tumor in breast and lymph nodes), immune markers (PDL1 on infiltrating immune cells (IIC) and on tumor cells (TC); CD8 in invasive margin and in tumor center) and apoptosis markers (bcl-2; mcl-2) were determined by immunohistochemistry (IHC; H-scores) in core biopsy sections obtained at primary diagnosis and at cycle 2. For multivariate logistic regression, each biomarker (separately), clinical factors (Ki-67, cT, cN) and therapy were entered. All analyses were exploratory. Results:Biomarkers were available in up to 326 patients (pts) at baseline and up to 170 pts at 3 weeks (due to low tumor content in 2nd core biopsy). Baseline IIC-PDL1 was associated with pCR in the T-DM1 arm (OR 2.89; 95%CI: 1.11-7.51); IIC-PDL1 at cycle 2 was not associated with pCR. PD-L1 expression in TC was rare (2%); cycle-2 TC-PD-L1 was associated with pCR in all pts and in the pooled TDM-1 arms. High baseline CD8 in tumor center was associated with pCR in the whole cohort (OR 2.4; CI: 1.04 – 5.5) and in the T+ET arm (OR=10.1; CI: 1.12 - 91.6) and at cycle 2 in all pts (OR=9.52; CI: 2.17 – 41), in pooled TDM-1 arms (OR=15.7; CI: 2.49 – 99), and in TDM-1+ET (OR=25.05; CI: 2.12 – 295). Increases in this marker also predicted pCR in all pts, pooled TDM-1, and in TDM-1+ET. Association of cycle-2 CD8 in tumor center with pCR persisted in multivariate models. Lower baseline CD8 in invasive margin was associated with pCR in the T-DM1 arm (OR=0.09; CI: 0.01-0.69), but at cycle 2 in all pts (OR=18.1; CI: 1.60 – 204) and in pooled TDM-1 arms (OR=23.5; CI: 1.1 - 500). This positive impact persisted in multivariate models. Bcl-2 expression at baseline was associated with non-pCR in all pts (OR=0.28, CI: 0.12 - 0.66), in the pooled T-DM1 arms (OR=0.216, CI: 0.08 - 0.61), and particularly in the T-DM1+ET arm (OR=0.14; CI: 0.03 - 0.71). This association persisted in multivariate analysis. At cycle 2, lower bcl-2 had OR=0.16 (CI: 0.03 - 0.96) in the pooled T-DM1 arms. No association with efficacy was seen for mcl-1. Conclusions: The WSG-ADAPT HER2+/HR+ phase II trial is the first international trial to focus on HER2+/HR+ EBC alone and the first to show substantial pCR rates of > 40% after only 12 weeks of T-DM1 -- without standard chemotherapy. Expression of bcl-2 may affect resistance to T-DM1. High immune activity at baseline and/or cycle 2 seems to be associated with pCR. The association of CD8 expression and its changes with therapy efficacy is complex and could depend on ET. Further biomarker analyses are ongoing and will be presented at the meeting. Citation Format: Harbeck N, Nitz UA, Matthias C, Kates R, Braun M, Kümmel S, Schumacher C, Potenberg J, Kraemer S, Kleine-Tebbe A, Augustin D, Aktas B, Forstbauer H, Tio J, Liedtke C, Grischke E-M, de Haas SL, Deurloo R, Schumacher J, Wuerstlein R, Kreipe HH, Gluz O. The role of immune and apoptosis markers for prediction of pCR in the WSG-ADAPT HER2+/HR+ phase II trial evaluating 12-weeks of neoadjuvant TDM1 ± endocrine therapy (ET) versus T + ET in HER2-positive hormone-receptor-positive early breast cancer (EBC) [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P1-09-05.
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- 2017
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19. International Consensus Conference for Advanced Breast Cancer, Lisbon 2019: ABC5 Consensus - Assessment by a German Group of Experts
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Johannes Ettl, Hans-Joachim Lück, Moritz Schwoerer, Lidia Perlova-Griff, Lothar Müller, Diana Lüftner, Eugen Ruckhäberle, Michael Untch, Eva Schumacher-Wulf, Katja Ziegler-Löhr, Peter A. Fasching, Christian M. Kurbacher, Isabel Radke, F Förster, Rachel Würstlein, Christoph Thomssen, Dieter Steinfeld-Birg, Doris Augustin, Susanne Briest, Renate Haidinger, Volkmar Müller, Norbert Marschner, Iris Scheffen, and Nadia Harbeck
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medicine.medical_specialty ,Advanced breast ,5th International Consensus Conference for Advanced Breast Cancer, Advanced breast cancer, Hormone receptor-positive and HER2-positive advanced breast cancer, BRCA-associated advanced breast cancer , Triple-negative advanced breast cancer, Personalized medicine ,German ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Medicine ,030212 general & internal medicine ,ddc:610 ,skin and connective tissue diseases ,Final version ,business.industry ,Consensus conference ,Cancer ,Conference Report ,Precision medicine ,medicine.disease ,language.human_language ,Oncology ,030220 oncology & carcinogenesis ,Family medicine ,language ,Surgery ,Personalized medicine ,business - Abstract
The 5th International Consensus Conference for Advanced Breast Cancer (ABC5) took place on November 14–16, 2019, in Lisbon, Portugal. Its aim is to standardize the treatment of advanced breast cancer based on the available evidence and to ensure that all breast cancer patients worldwide receive adequate treatment and access to new therapies. This year, the conference focused on developments and study results in the treatment of patients with hormone receptor-positive/HER2-negative breast cancer as well as precision medicine. As in previous years, patient advocates from around the world were integrated into the ABC conference and had seats on the ABC consensus panel. In the present paper, a working group of German breast cancer experts comments on the results of the on-site ABC5 consensus votes by ABC panelists regarding their applicability for routine treatment in Germany. These comments take the recommendations of the Breast Committee of the Gynecological Oncology Working Group (Arbeitsgemeinschaft Gynäkologische Onkologie; AGO) into account. The report and assessment presented here pertain to the preliminary results of the ABC5 consensus. The final version of the statements will be published in Annals of Oncology and The Breast.
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- 2019
20. Correction to: Reducing chemotherapy use in clinically high-risk, genomically low-risk pN0 and pN1 early breast cancer patients : five-year data from the prospective, randomised phase 3 West German Study Group (WSG) PlanB trial
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Ulrike Nitz, Oleg Gluz, Matthias Christgen, Ronald E. Kates, Michael Clemens, Wolfram Malter, Benno Nuding, Bahriye Aktas, Sherko Kuemmel, Toralf Reimer, Andrea Stefek, Fatemeh Lorenz-Salehi, Petra Krabisch, Marianne Just, Doris Augustin, Cornelia Liedtke, Calvin Chao, Steven Shak, Rachel Wuerstlein, Hans H. Kreipe, and Nadia Harbeck
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Adult ,Risk ,Cancer Research ,Adolescent ,Medizin ,Breast Neoplasms ,IHC4 ,Workflow ,Oncotype DX ,Young Adult ,Breast cancer ,Germany ,Biomarkers, Tumor ,Humans ,Genetic Predisposition to Disease ,Genomic signature ,Prospective Studies ,Aged ,Neoplasm Staging ,Randomized Controlled Trials as Topic ,Correction ,Middle Aged ,Clinical Trial ,Survival Analysis ,Treatment Outcome ,Oncology ,Clinical Trials, Phase III as Topic ,Chemotherapy, Adjuvant ,Ki-67 ,Female ,Neoplasm Grading - Abstract
Background The prospective phase 3 PlanB trial used the Oncotype DX® Recurrence Score® (RS) to define a genomically low-risk subset of clinically high-risk pN0-1 early breast cancer (EBC) patients for treatment with adjuvant endocrine therapy (ET) alone. Here, we report five-year data evaluating the prognostic value of RS, Ki-67, and other traditional clinicopathological parameters. Methods A central tumour bank was prospectively established within PlanB. Following an early amendment, hormone receptor (HR)+ , pN0-1 RS ≤ 11 patients were recommended to omit chemotherapy. Patients with RS ≥ 12, pN2-3, or HR-negative/HER2-negative disease were randomised to anthracycline-containing or anthracycline-free chemotherapy. Primary endpoint: disease-free survival (DFS). PlanB Clinicaltrials.gov identifier: NCT01049425. Findings From 2009 to 2011, PlanB enrolled 3198 patients (central tumour bank, n = 3073) with the median age of 56 years, 41.1% pN+, and 32.5% grade 3 EBC. Chemotherapy was omitted in 348/404 (86.1%) eligible RS ≤ 11 patients. After 55 months of median follow-up, five-year DFS in ET-treated RS ≤ 11 patients was 94% (in both pN0 and pN1) versus 94% (RS 12–25) and 84% (RS > 25) in chemotherapy-treated patients (p 2 cm, and RS, but not IHC4 or Ki-67 were independent adverse factors. If RS was excluded, IHC4 or both Ki-67 and PR entered the model. The impact of RS was particularly pronounced in patients with intermediate Ki-67 (>10%
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- 2019
21. LBA2 Impact of RNA expression signatures and tumour infiltrating lymphocytes (TILs) for pathological complete response (pCR) and survival after 12 week de-escalated neoadjuvant pertuzumab + trastuzumab ± paclitaxel in the WSG-HER2+/HR- ADAPT trial
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J. Potenberg, Rachel Wuerstlein, Doris Augustin, O Gluz, C. Kolberg-Liedtke, J. Palatty, Christine Eulenburg, U. Nitz, S. Kuemmel, E-M. Grischke, D. Ulbrich-Gebauer, Friedrich Feuerhake, C. Biehl, Matthias Christgen, Michael Braun, Nadia Harbeck, Monika Graeser, H.H. Kreipe, and R Kates
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business.industry ,Hematology ,chemistry.chemical_compound ,Rna expression ,Oncology ,Paclitaxel ,chemistry ,Trastuzumab ,medicine ,Cancer research ,Pertuzumab ,business ,Pathological ,Complete response ,medicine.drug - Published
- 2021
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22. A randomized phase III study evaluating pegylated liposomal doxorubicin versus capecitabine as first-line therapy for metastatic breast cancer: results of the PELICAN study
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Matthias W. Beckmann, Michael Untch, Mathias Warm, Paul R. Harnett, Hans-Joachim Lück, Nadia Harbeck, Steffen Saupe, Burkhard Otremba, Jana Barinoff, Lothar Müller, Michael Scholz, Marcus Schmidt, Salah-Eddin Al-Batran, Philipp Harter, Rolf Kreienberg, Julia Dorn, Elke Jäger, Dirk Waldenmaier, Maike de Wit, and Doris Augustin
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0301 basic medicine ,Oncology ,Cancer Research ,medicine.medical_treatment ,Medizin ,Polyethylene Glycols ,chemistry.chemical_compound ,0302 clinical medicine ,Risk Factors ,polycyclic compounds ,Neoplasm Metastasis ,skin and connective tissue diseases ,Aged, 80 and over ,Middle Aged ,Metastatic breast cancer ,Clinical Trial ,Treatment Outcome ,Paclitaxel ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,lipids (amino acids, peptides, and proteins) ,medicine.drug ,Adult ,PELICAN ,Antimetabolites, Antineoplastic ,medicine.medical_specialty ,Cyclophosphamide ,Breast Neoplasms ,Vinorelbine ,Capecitabine ,Young Adult ,03 medical and health sciences ,Breast cancer ,Pegylated liposomal doxorubicin ,Internal medicine ,medicine ,Humans ,ddc:610 ,Aged ,Neoplasm Staging ,Chemotherapy ,business.industry ,medicine.disease ,Survival Analysis ,030104 developmental biology ,chemistry ,Doxorubicin ,Quality of Life ,Methotrexate ,business - Abstract
Purpose: The PELICAN trial evaluates for the first time efficacy and safety of pegylated liposomal doxorubicin (PLD) versus capecitabine as first-line treatment of metastatic breast cancer (MBC). Methods: This randomized, phase III, open-label, multicenter trial enrolled first-line MBC patients who were ineligible for endocrine or trastuzumab therapy. Cumulative adjuvant anthracyclines of 360 mg/m² doxorubicin or equivalent were allowed. Left ventricular ejection fraction of >50 % was required. Patients received PLD 50 mg/m² every 28 days or capecitabine 1250 mg/m² twice daily for 14 days every 21 days. The primary endpoint was time-to-disease progression (TTP). Results: 210 patients were randomized (n = 105, PLD and n = 105, capecitabine). Adjuvant anthracyclines were given to 37 % (PLD) and 36 % (capecitabine) of patients. No significant difference was observed in TTP [HR = 1.21 (95 % confidence interval, 0.838–1.750)]. Median TTP was 6.0 months for both PLD and capecitabine. Comparing patients with or without prior anthracyclines, no significant difference in TTP was observed in the PLD arm (log-rank P = 0.64). For PLD versus capecitabine, respectively, overall survival (median, 23.3 months vs. 26.8 months) and time-to-treatment failure (median, 4.6 months vs. 3.7 months) were not statistically significantly different. Compared to PLD, patients on capecitabine experienced more serious adverse events (P = 0.015) and more cardiac events among patients who had prior anthracycline exposure (18 vs. 8 %; P = 0.31). Conclusion: Both PLD and capecitabine are effective first-line agents for MBC.
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- 2016
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23. Concordance rates of biomarkers uPA and PAI-1 results in primary breast cancer vs. consecutive tumor board decision and therapy performed in clinical hospital routine: Results of a prospective multi-center study at certified breast centers
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Brigitte Rack, A Wischnik, Thomas Kapitza, Peter Krase, Oliver Steinkohl, Cornelia Hoess, Marion Kiechle, Volker R. Jacobs, and Doris Augustin
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Adult ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Concordance ,Clinical Decision-Making ,Breast Neoplasms ,Young Adult ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Risk Factors ,Germany ,Internal medicine ,Plasminogen Activator Inhibitor 1 ,Biomarkers, Tumor ,Humans ,Medicine ,Tumor board ,Prospective Studies ,Positive test ,Aged ,Gynecology ,business.industry ,Age Factors ,Antineoplastic Protocols ,General Medicine ,Guideline ,Middle Aged ,medicine.disease ,Urokinase-Type Plasminogen Activator ,030104 developmental biology ,030220 oncology & carcinogenesis ,Multi center study ,Practice Guidelines as Topic ,Biomarker (medicine) ,Female ,Surgery ,Guideline Adherence ,business ,Primary breast cancer - Abstract
Objective Biomarkers uPA and PAI-1 are guideline recommended by ASCO (USA) and AGO (Germany) in primary breast cancer to avoid unnecessary CTX in patients at medium risk for recurrence. For clinical quality assurance of uPA/PAI-1 testing, analysis of test-therapy concordance was performed. Methods Prospective non-interventional multi-center study over 2 years among six Certified Breast Centers in Germany to investigate uPA/PAI-1 results in consecutive decision making for tumor board recommendation and actual therapy in uninfluenced clinical setting. Concordance and discordance rates of uPA/PAI-1 testing were calculated and individual reasons for decision making analyzed. Results Among n = 93 uPA/PAI-1 tests evaluated n = 42/93 (45.2%) were uPA + PAI-1 negative and n = 51/93 (54.8%) uPA and/or PAI-1 positive. In uPA + PAI-1 negative test results in n = 35/42 (83.3%) CTX was avoided as recommended. But in n = 7/42 (16.7%) CTX was performed despite, resulting in over treatment. In uPA and/or PAI-1 positive test results in n = 26/51 (51.0%) CTX was performed but in n = 25/51 (49.0%) not despite recommendation for CTX which is under treatment. The conformity of uPA/PAI-1 test result vs. tumor board decision was n = 73/93 (78.5%). The overall concordance of uPA/PAI-1 test result vs. consecutive therapy was n = 61/93 (65.6%). A variety of reasons for individual result-deviating decisions were identified. Conclusions Clinical quality assurance of uPA/PAI-1 biomarker testing showed inconsistency of test results with consecutive tumor board decision and/or final therapy performed in up to 1/3 of patients. To close this clinical quality gap in application of uPA/PAI-1 biomarkers, individual analysis of deviations is suggested with process optimization accordingly.
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- 2016
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24. ABC3 Consensus Commented from the Perspective of the German Guidelines
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Renate Haidinger, Johannes Ettl, HJ Lück, Rachel Wuerstlein, F Marmé, Diana Lüftner, Friedrich Overkamp, Michael Untch, Nadia Harbeck, Eugen Ruckhäberle, Norbert Marschner, Marc Thill, Lothar Müller, Doris Augustin, and C. Thomssen
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Gynecology ,medicine.medical_specialty ,business.industry ,Advanced breast ,Consensus conference ,Locally advanced ,Obstetrics and Gynecology ,Cancer ,medicine.disease ,Metastatic breast cancer ,language.human_language ,German ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Quality of life (healthcare) ,030220 oncology & carcinogenesis ,Family medicine ,Maternity and Midwifery ,language ,medicine ,030212 general & internal medicine ,business - Abstract
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.
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- 2016
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25. Abstract P6-17-08: Brain metastases in breast cancer network Germany (BMBC, GBG 79): First analysis of 548 patients from the multicenter registry
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A Stefek, H-H Dohmen, Doris Augustin, I Witzel, T Neunhöffer, Matthias Frank, R Weide, E Laakmann, TW Park-Simon, Felix Flock, T. Hesse, Martina Schmidt, Volker Moebus, Atanas Ignatov, S. Loibl, F Würschmidt, G. von Minckwitz, G Durmus, Nicole Burchardi, Thorsten Kühn, Tanja Fehm, and Volkmar Mueller
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Oncology ,Cancer Research ,medicine.medical_specialty ,Tumor biology ,business.industry ,Incidence (epidemiology) ,Cancer ,Disease ,medicine.disease ,Primary tumor ,Surgery ,Breast cancer ,Internal medicine ,Cohort ,medicine ,In patient ,business - Abstract
Background: The incidence of brain metastases (BM) in breast cancer patients is rising and has become a major clinical challenge. So far, limited therapeutic options and insights into the biology of BM exist since only a few studies analyzed exclusively data of breast cancer patients. In order to improve this situation, our multicenter registry was initiated in 2014: Brain Metastases in Breast Cancer Network Germany (BMBC, GBG79). Materials and Methods: Patients with BM diagnosed since 2000, a history of breast cancer and no history of other malignant or neurologic disease can be included. Registration is allowed retrospectively as well as prospectively into a web–based database ("MedCodes"). Characteristics of the primary tumor, metastatic disease and BM as well as treatment details are documented. For this first analysis, 548 patients from 39 German centers were included. Results: Median age at first diagnosis of BM was 55 years (25 – 90 years). 43% of patients (233/548) were HER2 positive, 19% (n=105) were triple–negative and 25% (n= 138) had luminal primary tumors indicating a selection of patients with specific tumor biology who develop BM. 54 % of the patients (n=267) had up to three BM whereas 45% (n=223) had more than three BM. 19% of patients (n=106) had BM without evidence of extracranial disease. 27% of the patients (n=146) underwent surgery of the BM. Of these patients, 61% (n= 89) were treated with whole brain radiotherapy and 16% (n=23) with stereotactic radiotherapy. In patients without surgery (n=397), 73% (n=289) received whole brain radiotherapy and 7% (n=28) stereotactic radiotherapy. Median time from diagnosis of primary breast cancer to BM was 38.5 month for the entire cohort (CI95% 35.4 – 43.3). The time from first diagnosis to BM was shorter for triple–negative patients (20.9 month, CI95% 15.5 – 25.9) compared with patients with HER2–positive (37.0 month, CI95% 30.5 – 42.0) or luminal tumors (48.3 month, CI95% 38.2 – 54.0) (p Conclusion: This is so far the largest analysis of breast cancer patients with BM treated in Germany. In this cohort, triple–negative subtype or more than three BM were associated with shorter survival from the diagnosis of BM. HER2 positive patients with no HER2 directed therapy after the diagnosis of BM showed a shorter survival. The recruitment of the registry is ongoing and we aim to include more than 1000 patients by the end of 2015. Citation Format: Witzel I, Loibl S, Laakmann E, Augustin D, Flock F, Dohmen H-H, Durmus G, Frank M, Hesse T, Ignatov A, Kühn T, Neunhöffer T, Park-Simon T-W, Schmidt M, Stefek A, Weide R, Würschmidt F, Fehm T, Moebus V, von Minckwitz G, Burchardi N, Mueller V. Brain metastases in breast cancer network Germany (BMBC, GBG 79): First analysis of 548 patients from the multicenter registry. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-17-08.
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- 2016
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26. ABC4 Consensus: Assessment by a German Group of Experts
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Christoph Thomssen, Diana Lüftner, Michael Untch, Nadia Harbeck, Doris Augustin, Rachel Wuerstlein, Volkmar Müller, Norbert Marschner, Eugen Ruckhäberle, Renate Haidinger, Susanne Briest, Lothar Müller, and Johannes Ettl
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medicine.medical_specialty ,Consensus ,business.industry ,media_common.quotation_subject ,Cancer ,medicine.disease ,Precision medicine ,language.human_language ,German ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Alliance ,Oncology ,030220 oncology & carcinogenesis ,Voting ,Family medicine ,medicine ,language ,Surgery ,030212 general & internal medicine ,Personalized medicine ,business ,Human Epidermal Growth Factor Receptor 2 ,media_common - Abstract
The Advanced Breast Cancer Fourth Consensus (ABC4) on diagnosis and treatment of advanced breast cancer (ABC) again took place in Lisbon, on November 2-4, 2017, and was chaired by Fatima Cardoso, MD, PhD. This year's contents focused very much on new developments in the treatment of ABC. For example, the significance of inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) in hormone receptor (HR)-positive ABC, of dual antibody blockade in human epidermal growth factor receptor 2 (HER2)-positive ABC, and of poly(ADP-ribose) polymerase (PARP) inhibition in triple-negative ABC, as well as the potential therapeutic consequences, were discussed. Other key issues were BRCA-associated breast cancer, treatment of brain metastases, and personalized therapy decision-making using molecular testing (so-called ‘precision medicine'). As in past years, an important objective of the ABC conference was cooperation with representatives of patient organizations from around the world. This cooperation was further intensified during the ABC4. Following the main conference, the ‘Global Alliance' was founded, with the goal of publicizing and coordinating measures necessary worldwide from the patient advocates' standpoint. - The ABC consensus inevitably cannot accommodate country-specific needs, due to the truly global expert panel. Therefore, a working group of German breast cancer experts commented - as in the past years - on the on-site voting results by the ABC panelists upon which the final ABC4 consensus will be based, with particular consideration of the German guidelines on diagnosis and treatment of breast cancer for everyday treatment in Germany.
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- 2018
27. Predictive role of HER2/neu, topoisomerase-II-alpha, and tissue inhibitor of metalloproteinases (TIMP-1) for response to adjuvant taxane-based chemotherapy in patients with intermediate-risk breast cancer: results from the WSG-AGO EC-Doc trial
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Fritz Jänicke, Hans Kreipe, Walther Kuhn, Doris Augustin, Ronald E. Kates, Jens Huober, Arndt Hartmann, Volker Möbus, Nils Brünner, Annette Bartels, Ulrike Nitz, Svjetlana Mohrmann, Oleg Gluz, E Pelz, Nadia Harbeck, Christoph Thomssen, Ramona Erber, Zehra Moustafa, Marion Kiechle, and Cornelia Liedtke
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Risk ,Oncology ,Cancer Research ,medicine.medical_specialty ,Receptor, ErbB-2 ,medicine.medical_treatment ,Aneuploidy ,Breast Neoplasms ,Kaplan-Meier Estimate ,Disease-Free Survival ,HER2/neu ,Breast cancer ,Antigens, Neoplasm ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Biomarkers, Tumor ,medicine ,Humans ,Proportional Hazards Models ,Gynecology ,Chemotherapy ,Tissue Inhibitor of Metalloproteinase-1 ,Taxane ,biology ,business.industry ,Middle Aged ,Prognosis ,medicine.disease ,DNA-Binding Proteins ,Chromosome 17 (human) ,DNA Topoisomerases, Type II ,Treatment Outcome ,Chemotherapy, Adjuvant ,Multivariate Analysis ,Cohort ,biology.protein ,Immunohistochemistry ,Female ,Taxoids ,business - Abstract
Taxane–anthracycline-based adjuvant chemotherapy is standard of care in patients with node-positive breast cancer (BC) but is also associated with severe side effects and significant costs. It is yet unclear, which biomarkers would predict benefit from taxanes and/or general chemoresistance. In this study, we investigate a large cohort of patients with intermediate-risk BC treated within the WSG EC-DOC Trial for the predictive impact of topoisomerase-II-alpha, HER2/neu, and TIMP-1. Tumor tissue was available in a representative cohort of 772 cases of the WSG EC-DOC Trial collective which compared 4xEC-4xDoc versus 6xCEF/CMF. In addition to hormone receptor status and Ki-67, HER2/neu+ and topoisomerase-II-alpha status using fluorescence in situ hybridisation (FISH) and immunohistochemistry, TIMP-1 using immunohistochemistry, and aneuploidy of chromosome 17 using FISH were evaluated and correlated with outcome and taxane benefit. There was significant superiority of EC-Doc over CEF regarding 5-year DFS (90 vs. 80 %, respectively, p = 0.006) particularly in patient subgroups defined by HR+, HER2/neu+, high proliferation (i.e., Ki-67 ≥ 20 %), patient age >50 years old and normal chromosome 17 status, high TIMP-1 and low topoisomerase-II-alpha protein expression. Significant prognostic factors in multivariate analysis were EC-Doc therapy (HR = 0.61; 95 %CI 0.38–0.986), age
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- 2015
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28. Meetings and Conferences
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Hans-Joachim Lück, Sherko Kümmel, Frederik Marmé, Eugen Ruckhäberle, Nadia Harbeck, Michael Untch, Martin Werner, Wolfgang J. Brauer, Marcus Schmidt, Diana Lüftner, Johannes Ettl, Renate Haidinger, Jose Maria Lasso, Doris Augustin, Angela A. García-Ruano, Christoph Thomssen, Esther Deleyto, Norbert Marschner, Urban Bromberger, Sylvia Timme, Mattea Reinisch, Marc Thill, Rachel Wuerstlein, Friedrich Overkamp, Lothar Müller, Martin Sillem, Barbara Heitzelmann, and Beyhan Ataseven
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Gynecology ,medicine.medical_specialty ,Oncology ,business.industry ,Family medicine ,medicine ,Surgery ,business - Published
- 2016
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29. Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study's primary analysis of 2573 patients
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Jose Chacon, Katja Ziegler-Löhr, Kamran Rashid, Stanley Madretsma, Hortense Laharie Mineur, Soo Hyeon Lee, Bohuslav Melichar, Jasna Pesic, Julia Hall, Jörg Schilling, Paola Morales Espinosa, Wendy Taylor, Francesco Cognetti, Doris Augustin, Ines Sandri, Laura Murillo Jaso, Alejandro Juarez Ramiro, Nora Artagaveytia, Rocio Reategui, Nataliia Voitko, Teresa Gamucci, Lisa H Barraclough, Jérôme Alexandre, Mohammed Butt, Frank Priou, A.J. van de Wouw, Cristina Marinela Oprean, Isabel Alonso, Suzana Vasovic, Fernando Roque, Marc Thill, Viktoria Dvornichenko, K. Bouzid, Idris Yucel, Andrea Stefek, Jose Manuel Lopez Vega, Daniil Stroyakovskiy, R. Chiara Forcignanò, Mohammed Harb, Andrzej Mruk, Jana Prausová, Lydia Dreosti, Prabir Chakraborti, Armando Santoro, Lee Wei Ching, Anna Tuczek, Jane Beith, Larisa Ciule, Hakan Bozcuk, Antonino Musolino, Hartmut Kristeleit, Clare Crowley, T.C. Kok, Dhurata Koroveshi, Natasha Mithal, Laura Garcia Sanchis, Stephan Henschen, Carmen Cañabate Arias, A. Contu, Antoaneta Tomova, Alper Sevinc, Helga Droogendijk, Gustavo Fernando Ismael, Konstantinos Papazisis, Laurent Gasnault, Sandra Bakker, Judit Kocsis, Bernd Christensen, Stephen Kelly, Rosana Jarcau, Christian Jackisch, George Fountzilas, Cyril Foa, Annebeth W. Haringhuizen, Silvia Neciosup, Juan Matos Santos, Finlander Rosales Osegueda, Robinson Rodriguez, Marcus Schmidt, Bart de Valk, Kathryn Wright, A.S. Dhadda, Elizabeth Sherwin, Sabino De Placido, Luigi Cavanna, Joelle Egreteau, Shazza Rehman, Giacomo Allegrini, Doerte Luedders, Poovandren Govender, Hugues Barletta, Iztok Takač, Yuraima Garcia, Michael Green, Geneviève Jolimoy, Marcela Urrego, Chanyoot Bandidwattanawong, Vito Lorusso, Annette van der Velden, Rene Muñoz, Djumhana Atmakusuma, Christos Papandreou, Craig Macmillan, Hassan Errihani, Iris Schrader, Isabelle Desmoulins, Jean-Marc Ferrero, Mohamed Idris, B. Ataseven, Andre Farrokh, Isabelle Moullet, Iain R. Macpherson, N. Al-Sakaff, Stephen Chia, Blanca Hernando Fernandez De Aranguiz, Lorena Lion, Alexandros Ardavanis, Ani Zlatareva-Petrova, Ernesto Pablo Korbenfeld, Hugo Castro, Mirta Garcia, Heike Passmann-Kegel, Lionel Uwer, Gary Richardson, Marion Paul, Georgia Demetriou, Andreas Köhler, V. Kovcin, Eliot Sims, Gerasimos Aravantinos, Adriana Dominguez, Daniel Rauch, Greta Beyer, Laurence J. C. van Warmerdam, Roberto Bordonaro, Raymond Ng, David Coeffic, Rostislav Vyzula, Bernard Leduc, Jozef Mardiak, Andrea Pigi, Ingo Runnebaum, Jose Angel Garcia Saenz, Areewan Somwangprasert, Cristina Llorca Ferrandiz, Coskun Hasan Senol, Martin Griesshammer, Friedrich Overkamp, Suzanne Nguyen, Maria Turdean, Udaiveer Panwar, Zsuzsanna Nagy, Francesco Giotta, Andreas Schneeweiss, Teresa Ramon y Cajal Asensio, Jae Hong Seo, Joohyuk Sohn, Jean-Philippe Jacquin, Daniela Grecea, Jasmina Nedovic, Arrate Plazaola Alcibar, Tadeusz Pienkowski, Jetske M. Meerum Terwogt, Elmar Stickeler, Hazem I. Assi, Vadim Shirinkin, Grzegorz Slomian, Etela Mišurová, Roberto Hegg, K. Friedrichs, Corinne Dagada, Jean-François Berdah, Fulden Yumuk, Alexandru Eniu, Amit Chakrabarti, Mathias Fehr, Christoph Salat, Dan Lungulescu, Heinrik Martin Strebel, Antonio Llombart Cussac, Rémy Largillier, Stefan Curescu, Albert von der Assen, Emmanuel Guardiola, Andras Csejtei, Tamas Hickish, Krzysztof Krzemieniecki, Yaroslav Shparyk, Ramon Perez Carrion, Michela Donadio, Purificacion Martinez del Prado, Sandra Franco, J.J. Braun, Michael Friedlander, Suhail Anwar, Thierry Petit, Sarah Smith, Rafael Gutierrez Pilarte, Laia Garrigos Cubells, Frans L. G. Erdkamp, Jedzada Maneechavakajorn, Mastura Yusof, Jocelyn Adams, Diana Cascallar, Luis Antonio Fernandez Morales, Max S. Mano, Simon Waters, Carlos Beato, Philippe Martin, Martin Hogg, Isabelle Sillet Bach, Monica Casalnuovo, Klara Mezei, Alexey Manikhas, Margarida Damasceno, Sergey Emelyanov, Gabriella Mariani, Kecman Gordana, Gianfilippo Bertelli, Ignacio Pelaez Fernandez, Damir Vrbanec, Maria Wagnerova, Johannes Petrus Jordaan, Marina Cazzaniga, Mustafa Deryal, Ruth Davis, Abdurrahman Isikdogan, Sanjay Raj, José Juan Illarramendi Mañas, Vinod Ganju, Maria Dolores Torregrosa Maicas, Glenda Ramos, Nugroho Prayogo, H. Orfeuvre, Filipovic S, Joke Tio, Andrew Redfern, M. Shing, Eduardo Yanez, Khalil Zaman, Jin-Seok Ahn, Dino Amadori, Bahriye Aktas, Miriam O'Connor, Uta Ringsdorf, Christophe Desauw, J. Gligorov, Jorge Corona, Michele De Laurentiis, Arthur Wischnik, Paolo Pedrazzoli, Katalin Boér, Caroline Archer, Anne Kendall, Ori Freedman, Maya Tsakova, Dana Lucia Stanculeanu, Kevin Patterson, Cathy Kelly, Nellie Lay Chin Cheah, X. Artignan, Anil A. Joy, Steffi Busch, Monica Nave, Bryan Hennessy, Lorenzo Livi, X. Pivot, R.J.B. Blaisse, Adolfo Murias Rosales, Juan Carlos Alcedo, Dalila Marcano, Emmanuel Beguier, Andreas Müller, László Csaba Mangel, Christina Schlatter, Fernando Gaion, Tjoung-Won Park-Simon, Sebastian Wojcinski, Ute Bückner, Florinel Badulescu, Cynthia Mayte Villarreal Garza, Rozenn Allerton, Mikhail Lichinitser, Damir Gugić, Manuela Rabaglio, Jens Kisro, Iris Scheffen, Vincent Phua, Marc A. Bollet, Giampaolo Biti, M. Verrill, Adrien Melis, Andrew M Wardley, Ali Arican, Hamdy A. Azim, Lelia-Eveline Bauer, Tsai-Wang Chang, Nik Hauser, René Lazaro González Mendoza, Dominique Jaubert, Samreen Ahmed, Mazhar Shah, János Szántó, Kunibert Latos, Xavier Pivot, Helen Gogas, Elona Juozaityte, Luca Moscetti, Helene Simon, Giacomo Carterni, Dan-Corneliu Jinga, Olivia Pagani, Elena Rota Caremoli, Esther Arbona, Cornelia Liedtke, Stylianos Kakolyris, Abdulla Alhasso, Omalkhair Abulkhair, Jose Ponce Lorenzo, Julian Singer, Tony Branson, Claudia Hänle, Ingvild Mjaaland, Chiun-Sheng Huang, Heri Fadjari, Jonathan Joffe, Laetitia Stefani, Dieter Lampe, Franck Burki, S. Lauer, Sabine Schmatloch, Gracieux Fernando, Dina Sakaeva, Christina Balser, Michael Martin, Nora Bittner, Andrea Heider, Antonio Frassoldati, Serafin Morales Murillo, Hakan Akbulut, Saad Tahir, Tilmann Lantzsch, Christine Brezden-Masley, Vanessa Helena, Tran Van Thuan, F.E. de Jongh, Roger K.C. Ngan, Elke Faust, Hugues Bourgeois, Flora Li Tze Chong, Nehal Masood, Keun Seok Lee, J. Bishop, Mathias Warm, Dimitris Mavroudis, Petrosian Veersamy, Judith Fraser, Andres Garcia-Palomo Perez, Heiko Graf, Vanesa Quiroga Garcia, Jyh-Cherng Yu, Maria Jose Villanueva Silva, Elke Simon, Diana Aleman, Kazim Uygun, Cosima Brucker, Michael Weigel, Volkmar Müller, Djohan Kurnianda, Duncan Wheatley, Amr Abdel Aziz, Benno Lex, Laura G. Estévez, Darren Teoh, María Isabel León, Noemia Afonso, Frances Yuille, Amelia Tienghi, Gernot Seipelt, Jose Alberto Nogueira, Dumitru Filip, Zafar Malik, Fatima Cardoso, Giorgio Cruciani, Winnie Yeo, Luis Vera, Santiago Gonzalez Santiago, Richard North, M.W. Dercksen, Zsolt Horváth, Noelia Martinez Jañez, Marta Mion, Marcela Ferrari, Natalia Valdiviezo, Oana Zveltlana Cojocarasu, Alessandra Morelle, Medy Tsalic, Sonia Pernas Simon, Christoph Maintz, Daniele Farci, Alvaro Edson Lessa, Jeremy Monge, Joseph Gligorov, Anthony Neal, Norberto Batista Lopez, Piotr Tomczak, Yesim Eralp, Kasan Seetalarom, Thitiya (Sirisinha) Dejthevaporn, Jamal Zekri, Steven John Proctor, Saira Nasim, Muireann Kelleher, Eftal Yucel, Quirine Clementine van Rossum-Schornagel, Linda Coate, Paolo Marchetti, Theresa Howe, Carlos Alberto Hernandez, Roberto Torres, Konstanta Timcheva, Evaristo Maiello, Anita Prechtl, Jamil Asselah, Branislav Bystricky, Kate Scatchard, Zeba Aziz, Jaroslava Leskova, Sherko Kuemmel, Paolo Bidoli, Richard Ashford, Piotr Sawrycki, Claude Bressac, Alberto Bottini, Pilar Lopez Alvarez, Nadine Dohollou, Alejandro Andres Acevedo Gaete, M. De Laurentiis, T.J. Smilde, Andrew Proctor, Catherine Prady, Michele Aieta, Jan Henry Svensson, Reda Garidi, Erik Wist, Antonia Perello Martorell, Mohammed Jaloudi, Graeme Lumsden, Eva-Maria Grischke, Ali Youssef, Annemieke van der Padt, Kadri Altundag, Christina Bechtner, Mireille Mousseau, Heba El Zawahry, Maartje Los, Alvydas Česas, Alfredo Falcone, Salima Hamizi, Franchette W P J van den Berkmortel, Cesar Estuardo Hernandez-Monroy, K.H. Jung, Swati Kulkarni, R.K. Agrawal, Hwei Chung Wang, Hany Eldeeb, Fredrika Killander, Jose Luis Alonso Romero, Antonio Pazzola, Daan ten Bokkel Huinink, Mario Campone, Beena C.R. Devi, Florence Dalenc, Pedro Jimenez Gallego, Mawin Vongsaisuwon, Timur Ceric, Chantal Bernard Marty, R. A. Popescu, J. van den Bosch, Luis Matamala, Sylvia Ruth, Maria Litwiniuk, Maria Lomas Garrido, Mark Churn, Christian Kersten, Francesco Del Piano, Eddie Herman Tanggo, Antonio Fernandez Aramburo, Kyung Hae Jung, Christos Papadimitriou, Hamdy Abdel Azeem, Patricia Bastick, Tobias Hesse, Maree Colosimo, Lucia Gonzalez Cortijo, Mark Verrill, Gligorov, J, Ataseven, B, Verrill, M, De Laurentiis, M, Jung, K. H, Azim, H. A, Al-sakaff, N, Lauer, S, Shing, M, Pivot, X., de Laurentiis, M, Jung, K, Azim, H, Al-Sakaff, N, Pivot, X, Koroveshi, D, Bouzid, K, Casalnuovo, M, Cascallar, D, Korbenfeld, E, Bastick, P, Beith, J, Colosimo, M, Friedlander, M, Ganju, V, Green, M, Patterson, K, Redfern, A, Richardson, G, Ceric, T, Gordana, K, Beato, C, Ferrari, M, Hegg, R, Helena, V, Ismael, G, Lessa, A, Mano, M, Morelle, A, Nogueira, J, Timcheva, K, Tomova, A, Tsakova, M, Zlatareva-Petrova, A, Asselah, J, Assi, H, Brezden-Masley, C, Chia, S, Freedman, O, Harb, M, Joy, A, Kulkarni, S, Prady, C, Gaete, A, Matamala, L, Torres, R, Yanez, E, Franco, S, Urrego, M, Gugic, D, Vrbanec, D, Melichar, B, Prausova, J, Vyzula, R, Pilarte, R, Leon, M, Munoz, R, Ramos, G, Azeem, H, Aziz, A, El Zawahry, H, Osegueda, F, Alexandre, J, Artignan, X, Barletta, H, Beguier, E, Berdah, J, Marty, C, Bollet, M, Bourgeois, H, Bressac, C, Burki, F, Campone, M, Coeffic, D, Cojocarasu, O, Dagada, C, Dalenc, F, Del Piano, F, Desauw, C, Desmoulins, I, Dohollou, N, Egreteau, J, Ferrero, J, Foa, C, Garidi, R, Gasnault, L, Guardiola, E, Hamizi, S, Jarcau, R, Jacquin, J, Jaubert, D, Jolimoy, G, Mineur, H, Largillier, R, Leduc, B, Martin, P, Melis, A, Monge, J, Moullet, I, Mousseau, M, Nguyen, S, Orfeuvre, H, Petit, T, Priou, F, Bach, I, Simon, H, Stefani, L, Uwer, L, Youssef, A, Aktas, B, von der Assen, A, Augustin, D, Balser, C, Bauer, L, Bechtner, C, Beyer, G, Brucker, C, Buckner, U, Busch, S, Christensen, B, Deryal, M, Farrokh, A, Faust, E, Friedrichs, K, Graf, H, Griesshammer, M, Grischke, E, Hanle, C, Heider, A, Henschen, S, Hesse, T, Jackisch, C, Kisro, J, Kohler, A, Kuemmel, S, Lampe, D, Lantzsch, T, Latos, K, Lex, B, Liedtke, C, Luedders, D, Maintz, C, Muller, V, Overkamp, F, Park-Simon, T, Paul, M, Prechtl, A, Ringsdorf, U, Runnebaum, I, Ruth, S, Salat, C, Scheffen, I, Schilling, J, Schmatloch, S, Schmidt, M, Schneeweiss, A, Schrader, I, Seipelt, G, Simon, E, Stefek, A, Stickeler, E, Thill, M, Tio, J, Tuczek, A, Warm, M, Weigel, M, Wischnik, A, Wojcinski, S, Ziegler-Lohr, K, Aravantinos, G, Ardavanis, A, Fountzilas, G, Gogas, H, Kakolyris, S, Mavroudis, D, Papadimitriou, C, Papandreou, C, Papazisis, K, Castro, H, Hernandez-Monroy, C, Ngan, R, Yeo, W, Bittner, N, Boer, K, Csejtei, A, Horvath, Z, Kocsis, J, Mangel, L, Mezei, K, Nagy, Z, Szanto, J, Atmakusuma, D, Fadjari, H, Kurnianda, D, Prayogo, N, Tanggo, E, Coate, L, Hennessy, B, Kelly, C, Martin, M, Nasim, S, O'Connor, M, Aieta, M, Allegrini, G, Amadori, D, Bidoli, P, Biti, G, Bordonaro, R, Bottini, A, Carterni, G, Cavanna, L, Cazzaniga, M, Cognetti, F, Contu, A, Cruciani, G, Donadio, M, Falcone, A, Farci, D, Forcignano, R, Frassoldati, A, Gaion, F, Gamucci, T, Giotta, F, Livi, L, Lorusso, V, Maiello, E, Marchetti, P, Mariani, G, Mion, M, Moscetti, L, Musolino, A, Pazzola, A, Pedrazzoli, P, Pigi, A, de Placido, S, Caremoli, E, Santoro, A, Tienghi, A, Ahn, J, Lee, K, Lee, S, Seo, J, Sohn, J, Cesas, A, Juozaityte, E, Cheah, N, Chong, F, Devi, B, Phua, V, Teoh, D, Ching, L, Yusof, M, Corona, J, Dominguez, A, Mendoza, R, Hernandez, C, Ramiro, A, Santos, J, Espinosa, P, Villarreal Garza, C, Errihani, H, Bakker, S, van den Berkmortel, F, Blaisse, R, Huinink, D, van den Bosch, J, Braun, J, Dercksen, M, Droogendijk, H, Erdkamp, F, Haringhuizen, A, de Jongh, F, Kok, T, Los, M, Madretsma, S, Terwogt, J, van der Padt, A, van Rossum-Schornagel, Q, Smilde, T, de Valk, B, van der Velden, A, van Warmerdam, L, van de Wouw, A, North, R, Kersten, C, Mjaaland, I, Wist, E, Aziz, Z, Masood, N, Rashid, K, Shah, M, Alcedo, J, Aleman, D, Neciosup, S, Reategui, R, Valdiviezo, N, Vera, L, Fernando, G, Roque, F, Strebel, H, Krzemieniecki, K, Litwiniuk, M, Mruk, A, Pienkowski, T, Sawrycki, P, Slomian, G, Tomczak, P, Afonso, N, Cardoso, F, Damasceno, M, Nave, M, Badulescu, F, Ciule, L, Curescu, S, Eniu, A, Filip, D, Grecea, D, Jinga, D, Lungulescu, D, Oprean, C, Stanculeanu, D, Turdean, M, Dvornichenko, V, Emelyanov, S, Lichinitser, M, Manikhas, A, Sakaeva, D, Shirinkin, V, Stroyakovskiy, D, Abulkhair, O, Zekri, J, Filipovic, S, Kovcin, V, Nedovic, J, Pesic, J, Vasovic, S, Ng, R, Bystricky, B, Leskova, J, Mardiak, J, Misurova, E, Wagnerova, M, Takac, I, Demetriou, G, Dreosti, L, Govender, P, Jordaan, J, Veersamy, P, Romero, J, Lopez, N, Arias, C, Chacon, J, Aramburo, A, Morales, L, Garcia, M, Estevez, L, Garcia-Palomo Perez, A, Garcia Saenz, J, Garcia Sanchis, L, Cubells, L, Cortijo, L, Santiago, S, De Aranguiz, B, Manas, J, Gallego, P, Cussac, A, Ferrandiz, C, Garrido, M, Alvarez, P, Vega, J, Del Prado, P, Janez, N, Murillo, S, Rosales, A, Jaso, L, Fernandez, I, Martorell, A, Carrion, R, Simon, S, Alcibar, A, Lorenzo, J, Garcia, V, Asensio, T, Maicas, M, Villanueva Silva, M, Killander, F, Svensson, J, Fehr, M, Hauser, N, Muller, A, Pagani, O, Passmann-Kegel, H, Popescu, R, Rabaglio, M, Rauch, D, Schlatter, C, Zaman, K, Chang, T, Huang, C, Wang, H, Yu, J, Bandidwattanawong, C, Maneechavakajorn, J, Seetalarom, K, Dejthevaporn, T, Somwangprasert, A, Vongsaisuwon, M, Akbulut, H, Altundag, K, Arican, A, Bozcuk, H, Eralp, Y, Idris, M, Isikdogan, A, Senol, C, Sevinc, A, Uygun, K, Yucel, E, Yucel, I, Yumuk, F, Shparyk, Y, Voitko, N, Jaloudi, M, Adams, J, Agrawal, R, Ahmed, S, Alhasso, A, Allerton, R, Anwar, S, Archer, C, Ashford, R, Barraclough, L, Bertelli, G, Bishop, J, Branson, T, Butt, M, Chakrabarti, A, Chakraborti, P, Churn, M, Crowley, C, Davis, R, Dhadda, A, Eldeeb, H, Fraser, J, Hall, J, Hickish, T, Hogg, M, Howe, T, Joffe, J, Kelleher, M, Kelly, S, Kendall, A, Kristeleit, H, Lumsden, G, Macmillan, C, Macpherson, I, Malik, Z, Mithal, N, Neal, A, Panwar, U, Proctor, A, Proctor, S, Raj, S, Rehman, S, Sandri, I, Scatchard, K, Sherwin, E, Sims, E, Singer, J, Smith, S, Tahir, S, Taylor, W, Tsalic, M, Wardley, A, Waters, S, Wheatley, D, Wright, K, Yuille, F, Alonso, I, Artagaveytia, N, Rodriguez, R, Arbona, E, Garcia, Y, Lion, L, Marcano, D, and Van Thuan, T
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0301 basic medicine ,Oncology ,Cancer Research ,Receptor, ErbB-2 ,medicine.medical_treatment ,Medizin ,Antineoplastic Agent ,0302 clinical medicine ,Breast cancer ,Trastuzumab ,Adjuvant ,Aged, 80 and over ,education.field_of_study ,Middle Aged ,HER2/neu ,Tolerability ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Herceptin ,Subcutaneous ,subcutaneous ,Female ,Survival Analysi ,Breast Neoplasm ,medicine.drug ,Human ,Adult ,medicine.medical_specialty ,Injections, Subcutaneous ,Population ,Socio-culturale ,Antineoplastic Agents ,Breast Neoplasms ,Injections, Subcutaneou ,03 medical and health sciences ,Young Adult ,Internal medicine ,medicine ,Adjuvant therapy ,Humans ,Subcutaneou ,education ,Adverse effect ,Aged ,Chemotherapy ,Adjuvant, breast cancer, HER2/neu, herceptin ,trastuzumab ,business.industry ,medicine.disease ,Survival Analysis ,Surgery ,Discontinuation ,030104 developmental biology ,business - Abstract
Aim To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin ® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Methods Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. Results In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. Conclusion SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC.
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- 2017
30. Patients' preferences for subcutaneous trastuzumab versus conventional intravenous infusion for the adjuvant treatment of HER2-positive early breast cancer: final analysis of 488 patients in the international, randomized, two-cohort PrefHer study
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Thomas Bachelot, Alberto Ballestrero, Marco Colleoni, José Valero Alvarez, Amer Sami, Celalettin Camci, Rodrigo Lastra del Prado, Luis De La Cruz Merino, Antonio Bernardo, Peter Barrett-Lee, Yolanda Fernández Pérez, Vladimir Semiglazov, Thierry Petit, Mette Holck Nielsen, C. Langridge, Guillermo López Vivanco, Nik Hauser, Ignacio Porras Quintela, José Manuel Pérez García, Anna-Karin Wennstig, Victoria Dvornichenko, Erik Jakobsen, Guzel Mukhametshina, Heiko Graf, V. Jenkins, Mireille Mousseau, Alfonso Sanchez Muñoz, Pehr Lind, Irina Bulavina, Alexey Manikhas, Bengt Norberg, Xavier Pivot, Per Edlund, Sandeep Sehdev, Valerie Jenkins, Santos Enrech Frances, Nadia Califaretti, V. Müller, G. Curigliano, Duncan Wheatley, Stephen L. Chan, Enrique Espinosa Arranz, S. Osborne, Soeren Linnet, Nana Scotto, J. Gligorov, Volkmar Müller, Tjoung-Won Park-Simon, Karen McAdam, Ann Knoop, Giuseppe Curigliano, X. Pivot, Justine Kilkerr, Georg Heinrich, L. Fallowfield, Francisco Carabantes Ocon, Christopher Wolf, Robert El-Maraghi, Hugues Bourgeois, Christelle Levy, Luca Gianni, Russell Burcombe, Vadim Shirinkin, Huseyin Abali, Etienne Brain, Christoph Tausch, Lidia Perlova-Griff, Claudia Plesse Lefeuvre, Joseph Gligorov, Mikhail Lichinitser, Friedrich Overkamp, S. Verma, Kathryn Monson, Angela Stefania Ribecco, Doris Augustin, Lesley Fallowfield, Saad Tahir, Javier Cassinello Espinosa, Marcus Schmidt, Jacek Jassem, Laurent Zelek, Ruchan Uslu, Richard Simcock, Sherko Kuemmel, Javier Salvador Bofill, A. Knoop, Hervé Bonnefoi, Fikret Arpaci, Silvana Spadafora, Sunil Verma, Hendrik Kroening, and Elżbieta Brewczynska
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Adult ,Male ,medicine.medical_specialty ,Receptor, ErbB-2 ,Injections, Subcutaneous ,medicine.medical_treatment ,RC0280.B8 ,Population ,Breast Neoplasms ,Antibodies, Monoclonal, Humanized ,Disease-Free Survival ,HER2/neu ,Cohort Studies ,RC0254 ,RM0147 ,Breast cancer ,Trastuzumab ,Internal medicine ,Clinical endpoint ,medicine ,Humans ,skin and connective tissue diseases ,Infusions, Intravenous ,Adverse effect ,education ,neoplasms ,Aged ,education.field_of_study ,biology ,business.industry ,Hematology ,Middle Aged ,medicine.disease ,Surgery ,Treatment Outcome ,Oncology ,Cohort ,biology.protein ,Female ,business ,Adjuvant ,medicine.drug - Abstract
Patients with HER2-positive early breast cancer (EBC) preferred subcutaneous (s.c.) trastuzumab, delivered via single-use injection device (SID), over the intravenous (i.v.) formulation (Cohort 1 of the PrefHer study: NCT01401166). Here, we report patient preference, healthcare professional satisfaction, and safety data pooled from Cohort 1 and also Cohort 2, where s.c. trastuzumab was delivered via hand-held syringe.Patients were randomized to receive four adjuvant cycles of 600 mg fixed-dose s.c. trastuzumab followed by four cycles of standard i.v. trastuzumab, or vice versa. The primary endpoint was overall preference proportions for s.c. or i.v., assessed by patient interviews in the evaluable ITT population.A total of 245 patients were randomized to receive s.c. followed by i.v. and 243 received i.v. followed by s.c. (evaluable ITT populations: 235 and 232 patients, respectively). s.c. was preferred by 415/467 [88.9%; 95% confidence interval (CI) 85.7-91.6; P0.0001; two-sided test against null hypothesis of 65% s.c. preference]; 45/467 preferred i.v. (9.6%; 95% CI 7-13); 7/467 indicated no preference (1.5%; 95% CI 1-3). Clinician-reported adverse events occurred in 292/479 (61.0%) and 245/478 (51.3%) patients during the pooled s.c. and i.v. periods, respectively (P0.05; 2 × 2 χ(2)); 16 patients (3.3%) in each period experienced grade 3 events; none were grade 4/5.PrefHer revealed compelling and consistent patient preferences for s.c. over i.v. trastuzumab, regardless of SID or hand-held syringe delivery. s.c. was well tolerated and safety was consistent with previous reports, including the HannaH study (NCT00950300). No new safety signals were identified compared with the known i.v. profile in EBC. PrefHer and HannaH confirm that s.c. trastuzumab is a validated and preferred option over i.v. for improving patients' care in HER2-positive breast cancer.NCT01401166.
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- 2014
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31. Prospective multi-center study for quantification of chemotherapies and CTX-related direct medication costs avoided by use of biomarkers uPA and PAI-1 in primary breast cancer
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Volker R. Jacobs, A Wischnik, Cornelia Höss, Doris Augustin, Marion Kiechle, Oliver Steinkohl, Thomas Kapitza, Peter Krase, and Brigitte Rack
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Adult ,Oncology ,medicine.medical_specialty ,Cost-Benefit Analysis ,Antineoplastic Agents ,Breast Neoplasms ,Drug Costs ,Indirect costs ,Breast cancer ,Quality of life ,Internal medicine ,Granulocyte Colony-Stimulating Factor ,Plasminogen Activator Inhibitor 1 ,medicine ,Humans ,Prospective Studies ,Chemotherapy-Induced Febrile Neutropenia ,health care economics and organizations ,Aged ,Aged, 80 and over ,Gynecology ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,Urokinase-Type Plasminogen Activator ,Chemotherapy, Adjuvant ,Concomitant ,Multi center study ,Practice Guidelines as Topic ,Biomarker (medicine) ,Female ,Surgery ,Guideline Adherence ,Primary breast cancer ,business ,Febrile neutropenia - Abstract
Biomarkers uPA/PAI-1 as recommended by ASCO and AGO are used in primary breast cancer to avoid unnecessary CTX in medium risk-recurrence patients. This study verified how many CTX cycles and CTX-related direct medication costs can be avoided by uPA/PAI-1 testing. A prospective, non-interventional, multi-center study was performed among six Certified Breast Centers to analyze application of uPA/PAI-1 and consecutive decision-making. CTX avoided were identified and direct costs for CTX, CTX-related concomitant medication and febrile neutropenia (FN) prophylaxis with G-CSF calculated. In n = 93 breast cancers n = 35 CTX (37.6%) with 210 CTX cycles were avoided according to uPA/PAI-1 test result. uPA/PAI-1 testing saved direct medication costs for CTX of 177,453 €, CTX-related concomitant medication of 27,482 € and FN prophylaxis of 20,599 €, overall 225,534 €. At test costs at 287.50 € uPA/PAI-1 testing resulted in additional costs of 26,737.50 €. uPA/PAI-1 has proven to be cost-effective at a return-on-investment ratio of 8.4:1. Indirect cost savings further increase this ROI. These results support decision-making for cost-effective diagnostics and therapy in breast cancer.
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- 2013
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32. Final analysis of the prospective WSG-AGO EC-Doc versus FEC phase III trial in intermediate-risk (pN1) early breast cancer: efficacy and predictive value of Ki67 expression
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Jens Huober, Michael Scholz, G. Hoffmann, S. Böhmer, Oleg Gluz, D. Wallwiener, A. du Bois, Ronald E. Kates, E. Weiss, Hans Kreipe, Doris Augustin, B. Lisboa, Walther Kuhn, R. Kreienberg, Fritz Jänicke, Nadia Harbeck, A. Hartmann, D. Sattler, U. Nitz, C Thomssen, Marion Kiechle, Svjetlana Mohrmann, Ramona Erber, and Volker Möbus
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0301 basic medicine ,Oncology ,Adult ,medicine.medical_specialty ,Cyclophosphamide ,Adolescent ,Breast Neoplasms ,Docetaxel ,03 medical and health sciences ,Young Adult ,Breast cancer ,0302 clinical medicine ,Predictive Value of Tests ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Clinical endpoint ,Biomarkers, Tumor ,Medicine ,Humans ,Early breast cancer ,Aged ,Epirubicin ,Neoplasm Staging ,Gynecology ,Taxane ,business.industry ,Hazard ratio ,Hematology ,Middle Aged ,medicine.disease ,Chemotherapy regimen ,Predictive value ,030104 developmental biology ,Ki-67 Antigen ,Treatment Outcome ,Chemotherapy, Adjuvant ,030220 oncology & carcinogenesis ,Disease Progression ,Female ,Taxoids ,Fluorouracil ,business ,Intermediate risk ,medicine.drug - Abstract
Background Taxane-based adjuvant chemotherapy is standard in node-positive (N+) early breast cancer (BC). The magnitude of benefit in intermediate-risk N+ early BC is still unclear. WSG-AGO epiribicine and cyclophosphamide (EC)-Doc is a large trial evaluating modern taxane-based chemotherapy in patients with 1–3 positive lymph nodes (LNs) only. Patients and methods A total of 2011 BC patients (18–65 years, pN1) were entered into a randomized phase III trial comparing 4 × E90C600 q3w followed by 4 × docetaxel100 q3w (n = 1008) with the current standard: 6 × F500E100C500 q3w (n = 828) or C600M40F600 d1, 8× q4w (n = 175). Primary end point was event-free survival (EFS); secondary end points were overall survival (OS), toxicity, translational research, and quality of life. Central tumor bank samples were evaluable in a representative collective (n = 772; 40%). Ki-67 was assessed centrally in hormone receptor-positive disease as a surrogate marker for the distinction of luminal A/B-like tumors. Results Baseline characteristics were well balanced between study arms in both main study and central tumor bank subset. At 59-month median follow-up, superior efficacy of EC-Doc [versus FEC (a combination of 5-fluorouracil, epirubicin, and cyclophosphamide)] was seen in EFS and OS: 5-year EFS: 89.8% versus 87.3% (P = 0.038); 5-year OS: 94.5% versus 92.8% (P = 0.034); both tests one-tailed. EC-Doc caused more toxicity. In hormone receptor-positive (HR)+ disease, only high-Ki-67 tumors (≥20%) derived significant benefit from taxane-based therapy: hazard ratio = 0.39 (95% CI 0.18–0.82) for EC-Doc versus FEC (test for interaction; P = 0.01). Conclusion EC-Doc significantly improved EFS and OS versus FEC in intermediate-risk BC (1–3 LNs) within all subgroups as defined by local pathology. In HR+ disease, patients with luminal A-like tumors may be potentially over-treated by taxane-based chemotherapy. Clinical Trial number ClinicalTrials.gov, NCT02115204.
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- 2016
33. Prospektive Phase-III PlanB-Studie: 5 Jahres Daten zum prognostischen Stellenwert von 21-Gen Recurrence-Score, zentralpathologischem Grading, ER, PR, Ki-67 Review beim frühem Hochrisiko HR+/HER2-negativen Mammakarzinom
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Rachel Würstlein, R Kates, S Kümmel, Bahriye Aktas, M Clemens, U Nitz, Benno Nuding, Stefan Krämer, N Harbeck, Doris Augustin, Christer Svedman, F Lorenz-Salehi, Toralf Reimer, Petra Krabisch, O Gluz, Marianne Just, S Shak, HH Kreipe, Cornelia Liedtke, and Matthias Christgen
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- 2016
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34. ABC3 Consensus: Assessment by a German Group of Experts
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Nadia Harbeck, Renate Haidinger, Christoph Thomssen, Norbert Marschner, Rachel Wuerstlein, Michael Untch, Doris Augustin, Eugen Ruckhäberle, Lothar Müller, Marc Thill, Hans-Joachim Lück, Diana Lüftner, Johannes Ettl, Friedrich Overkamp, and Frederik Marmé
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medicine.medical_specialty ,Coping (psychology) ,Consensus ,media_common.quotation_subject ,German ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,Breast cancer ,Voting ,medicine ,030212 general & internal medicine ,media_common ,Gynecology ,business.industry ,Cancer ,medicine.disease ,Metastatic breast cancer ,language.human_language ,Oncology ,030220 oncology & carcinogenesis ,Scale (social sciences) ,Family medicine ,language ,Surgery ,business - Abstract
The Advanced Breast Cancer Third International Consensus Conference on the diagnosis and treatment of advanced breast cancer took place in Lisbon, Portugal, on November 5-7, 2015. This year's conference (ABC3) was focused on the treatment of metastatic breast cancer (stage IV), as it was 4 years ago at the first consensus meeting (ABC1). A matter of particular interest was the patients' perspective. Thus, patient-relevant issues were addressed by the consensus discussions, such as those on treatment goals, quality of life, care of long-term survivors (‘survivorship issues'), and coping with disease-related symptoms and the side effects of treatment. Further important issues on the agenda were the use of standardized instruments for the assessment of individual treatment success (‘patient-reported outcome measures') and the evaluation of the benefit of novel drugs (e.g. the European Society for Medical Oncology (ESMO) Magnitude of Clinical Benefit Scale). Diagnosis and treatment of inoperable locally advanced breast cancer had already been discussed 2 years earlier at the ABC2 Consensus and were not dealt with in the framework of this year's ABC3 Consensus. With regard to country-specific peculiarities, which unavoidably found their way into the ABC Consensus, a working group of German breast cancer experts commented on the voting results of the ABC panelists. As for the past consensus, the group specially considered the German guidelines for the diagnosis and treatment of breast cancer (AGO (Gyneco-Oncology Working Group), S3, DGHO (German Society of Hematology and Medical Oncology)) in order to adapt the ABC3 consensus for everyday therapy in Germany.
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- 2016
35. Update on Female Cancer in Africa: The AORTIC Conference 2015, Morocco
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Christoph Thomssen, Renate Haidinger, Doris Augustin, Mattea Reinisch, Diana Lüftner, Angela A. García-Ruano, Wolfgang J. Brauer, Michael Untch, Norbert Marschner, Sylvia Timme, Urban Bromberger, Eugen Ruckhäberle, Hans-Joachim Lück, Frederik Marmé, Rachel Wuerstlein, Jose Maria Lasso, Nadia Harbeck, Johannes Ettl, Martin Werner, Friedrich Overkamp, Esther Deleyto, Marcus Schmidt, Sherko Kümmel, Lothar Müller, Martin Sillem, Marc Thill, Barbara Heitzelmann, and Beyhan Ataseven
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Gynecology ,medicine.medical_specialty ,business.industry ,Cancer ,medicine.disease ,Congress Report ,03 medical and health sciences ,0302 clinical medicine ,Oncology ,030220 oncology & carcinogenesis ,Family medicine ,medicine ,Surgery ,030212 general & internal medicine ,skin and connective tissue diseases ,business - Published
- 2016
36. Abstract P5-15-04: CTX and CTX-related direct medication costs saved by testing biomarkers uPA and PAI-1 in primary breast cancer: Results of a prospective multi-center study at Certified Breast Centers in Germany
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Doris Augustin, Marion Kiechle, C Hoess, P Krase, T Kapitza, O Steinkohl, A Wischnik, Brigitte Rack, and Volker R. Jacobs
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Gynecology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Cancer ,Guideline ,medicine.disease ,Indirect costs ,Regimen ,Breast cancer ,Oncology ,Quality of life ,Internal medicine ,Concomitant ,Health care ,medicine ,business - Abstract
Background: Biomarkers uPA and PAI-1 are guideline recommended by ASCO, USA, and AGO, Germany, to be used in primary breast cancer to avoid unnecessary CTX in medium risk recurrence patients [G2, N−, HR+, HER2neu−, >35 years]. This study was performed to verify in normal clinical settings how many CTX cycles and how much CTX-related direct medication costs can be avoided by uPA/PAI-1 testing. Methods: Prospective, non-interventional, multi-center study over two years among six Certified Breast Centers in Germany to analyze application of uPA/PAI-1 and consecutive decision making in the clinical setting for AOK Bayern-insured patients. CTX regimen and cycles avoided were identified for each case and direct costs for CTX and CTX-related medication costs for concomitant medication calculated for each patient individually according to body weight and body surface as well as potential FN prophylaxis according to physicians' decision. All medication costs were taken from the pharmaceutical price list for Germany Rote Liste of 2012. EURO [€] to US Dollar conversion rate as of June 12 2012: € 1.00 = US$ 1.25. Results: In n=93 breast cancers n=35 CTX (37.6%; FEC n=25, FEC+DOC n=8 and TC n=2) were avoided according to uPA/PAI-1 test result. Consecutively 210 CTX cycles or 12.1 years of CTX application were saved improving patients' quality of life. uPA/PAI-1 testing saved direct medication costs for avoided CTX of US$ 221.816, CTX-related concomitant medication of US$ 34.353 and G-CSF prophylaxis of US$ 25.749, overall US$ 281.918. At process costs for a single uPA/PAI-1 test calculated at US$ 359, uPA/PAI-1 testing resulted in additional costs of US$ 33.387 for all breast cancer cases. Overall, testing of uPA/PAI-1 has been proven to be cost-effective regarding direct medication costs alone at a return-on-investment ratio of 8.4:1. Indirect cost savings further increase this ROI. Conclusions: Innovative and individual cancer diagnostics like biomarkers uPA/PAI-1 can decrease need of CTX and increase patients' quality of life and thereby reduce costs for health care systems. Since application of this test is inadequate at present time measures are suggested to fully implement such cost-effective diagnostics. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-15-04.
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- 2012
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37. Abstract P1-13-13: First planned efficacy analysis of the NNBC 3-Europe trial: Addition of docetaxel to anthracycline containing adjuvant chemotherapy in high risk node-negative breast cancer patients
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Martina Schmidt, Nadia Harbeck, Corinne Veyret, Daniela Paepke, M. Schmitt, C. Thomssen, EJ Kantelhardt, W Meinerz, G. von Minckwitz, W. Wiest, Martina Vetter, P M Martin, Fcgj Sweep, Volker Hanf, G Hoffmann, Fritz Jaenicke, Doris Augustin, and Christoph Meisner
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Oncology ,Cancer Research ,medicine.medical_specialty ,education.field_of_study ,Chemotherapy ,Anthracycline ,business.industry ,medicine.medical_treatment ,Population ,Cancer ,medicine.disease ,Surgery ,Breast cancer ,Docetaxel ,Internal medicine ,medicine ,Clinical endpoint ,business ,education ,Mastectomy ,medicine.drug - Abstract
Background: Risk assessment in node-negative (N0) breast cancer patients (pts) is routinely performed by established clinico-pathological algorithms (CP) (Schmidt et al. Ann Oncol 2009). ASCO guidelines also recommend invasion markers uPA/PAI-1 (UP; Harris et al. JCO 2007). The prospective randomized multicenter NNBC 3-Europe trial had two questions: 1) Does UP compared to the CP algorithm improve identification of low-risk node-negative breast cancer patients? 2) Does addition of taxanes to adjuvant chemotherapy improve DFS probability in high-risk node-negative breast cancer? Data are mature to report on the second question only. Methods: Between 2002 and 2009, 4,147 node-negative breast cancer pts were recruited. Risk assessment was performed by CP (43 %) or by UP (57 %). High-risk pts were randomized to receive FE100C*3-Doc*3 (FEC-D) versus FE100C*6 (FEC) as adjuvant chemotherapy. Primary endpoint was disease-free survival probability (DFS). It was planned to accrue 2,572 pts allowing detection of 4% reduction in recurrence probability at 5 years with a power of 80 % at a level of α=0.05 (LogRank) after a minimum observation time of 2.5 years for every recruited patient. Results: In the intent-to-treat population (ITT, n=2,541), 1,286 high-risk pts received FEC-D, and 1,255 received FEC. In July 2012, 90.8 % of patients had reached the minimum observation time – median follow-up was 43.8, and 44.4 months. Main patients' characteristics were distributed similarly between the two chemotherapy arms: median age was 53 yrs, 37.4 % of pts were premenopausal, median tumor size was 1.90 cm, grade 3 was seen in 53.8 %, hormone receptor status was negative in 30.1 % and HER2 was overexpressed in 20.0 %. Mastectomy was performed in 11 %. All planned courses of FEC-D were given in 84.4 %, of FEC in 91.4 % (p < 0.0001). DFS after 2.5 yrs was for FEC-D 97.5 % (+/− 0.45 %) and for FEC 97.3 % (+/− 0.47 %). Overall-survival probability (OS) after 2.5 yrs was 99.0 % (+/− 0.29 %) for FEC-D and 99.5 % (+/− 0.20 %) for FEC. The survival differences between the two arms were not statistically significant. Per-protocol analysis did not reveal any additional results. Conclusions: Use of taxanes does not further reduce the rate of early recurrences and led to significantly more treatment discontinuation. Today, with adequate adjuvant chemotherapy even high-risk node-negative breast cancer patients have an excellent prognosis. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-13.
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- 2012
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38. Abstract P1-13-02: Analysis of the NNBC 3-Europe trial: Addition of docetaxel to anthracycline containing adjuvant chemotherapy in high risk node-negative breast cancer patients
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Manfred Schmitt, Doris Augustin, Daniela Paepke, Christoph Meisner, Corinne Veyret, Gunter von Minchwitz, EJ Kantelhardt, Volker Hanf, Martina Vetter, Nadia Harbeck, Pierre-Marie Martin, Fritz Jaenicke, Marcus Schmidt, Fred C.G.J. Sweep, and Christoph Thomssen
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Oncology ,Cancer Research ,medicine.medical_specialty ,Anthracycline ,Adjuvant chemotherapy ,business.industry ,medicine.disease ,Node negative ,Breast cancer ,Docetaxel ,Internal medicine ,medicine ,business ,medicine.drug - Abstract
Withdrawn by Author Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P1-13-02.
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- 2012
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39. Abstract P2-10-08: Prospective comparison of Recurrence Score and different definitions of luminal subtypes by central pathology assessment of single markers in early breast cancer: results from the phase III WSG-planB Trial
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Michael J. Clemens, Nadia Harbeck, S Markmann, S Shak, O Gluz, Bahriye Aktas, Ronald E. Kates, U. Nitz, Doris Augustin, M Salem, Cornelia Liedtke, Matthias Christgen, C. Thomssen, Christoph Uleer, H.H. Kreipe, and B Liedtke
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Cancer Research ,Chemotherapy ,Pathology ,medicine.medical_specialty ,business.industry ,Concordance ,medicine.medical_treatment ,Recurrence score ,Cancer ,Guideline ,Gene signature ,medicine.disease ,Oncology ,Medicine ,Clinical significance ,business ,Early breast cancer - Abstract
Background: Routine use of multigene RT-PCR based assays as Recurrence Score (RS) vs. single markers (grade, uPA/PAI-1, HR, HER2, Ki-67) is controversially discussed in early BC. Several definitions of luminal A/B subtypes have been proposed by St. Gallen guidelines and individual researchers (grade 1/2 vs. 3, Ki-67 cut-offs 14 or 20%). Recently, integration of PR>20% was proposed as an immunhistochemical luminal A subtype definition (Ki-67 Methods: planB trial (04/09 to 11/11: n=2,449 randomized for 6xTC vs. 4xEC-4xDOC in locally HER2− BC; n=3197 registered; n=3072 available for central tumor bank). RS was used as selection criterion for chemotherapy (CTx) omission in HR+ BC (if RS Results: RS distribution in 2569 HR+ tumors: 0–11 (18%), 12–25 (60%), >25 (22%) (RS1853%/34%/13%). Luminal A subtype based on Ki-67 cut-off of 20% was included in the luminal A/Ki-67 Luminal A/B based on local/central grade: 79%/21%; 67.9%/32.1%. In 354 pN0-1 patients, CTx was omitted based on low RS (88% compliance). In this group, 62% were high-risk by clinical-pathological criteria. Allocation to luminal A/B subtypes based on local/central grade varied substantially: overall concordance was 72%, but 40% of locally luminal B (HR+/G3) were luminal A (HR+/G1/2) by central and 60% of centrally luminal B were luminal A locally. Moderate correlations were found between RS and central grade (Spearman correlation rs=0.317; p < 0.001), local grade (0.321; p < 0.001) and Ki-67 (rs = 0.374; p < 0.001), particularly due to poor correlations in the RS group Inclusion of PR>20% moderately improved the correlation between luminal subtypes and RS to rs=0.34; p < 0.001. Data on allocation to luminal subtypes by local/central Ki-67 will be presented at the meeting. Conclusions: Our results represent the first prospective correlation of different luminal A/B definitions vs. a guideline mentioned gene signature (RS). High RS usually implies high grade and luminal B classification, the converse is not true. There is substantial heterogeneity in risk assessment by luminal A/B classification and grade in low/intermediate RS groups. Concordance for central/local assessment of grade and luminal A/B status was limited. There is strong need for standardization of molecular subtype's immunhistochemical/clinical definition prior to implementation into daily routine. Clinical significance of these findings will be addressed by further follow up of the WSG-planB trial. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-10-08.
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- 2012
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40. Abstract P5-14-06: Analysis of test-therapy concordance for biomarkers uPA and PAI-1 in primary breast cancer in clinical hospital routine: Results of a prospective multi-center study at Certified Breast Cancers in Germany
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A Wischnik, C Hoess, Doris Augustin, Volker R. Jacobs, T Kapitza, P Krase, O Steinkohl, Brigitte Rack, and Marion Kiechle
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Gynecology ,Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Concordance ,Cancer ,Guideline ,medicine.disease ,Negative Test Result ,Test (assessment) ,Internal medicine ,Multi center study ,medicine ,Medium Risk ,Primary breast cancer ,business - Abstract
Objective: Biomarkers uPA and PAI-1 are guideline recommended by ASCO, USA, and AGO, Germany, to be used in primary breast cancer to avoid unnecessary CTX in medium risk recurrence patients [G2, N−, HR+, Her2neu−, >35 years]. For quality assurance of uPA/PAI-1 testing an analysis of test-therapy concordance was performed. Methods: Prospective, non-interventional, multi-center study over two years among six Certified Breast Centers in Germany to analyze application of uPA/PAI-1 and use of the result in consecutive decision making in Tumor Board decision and actual therapy in the clinical setting for AOK Bayern-insured patients. Concordance and discordance rates of uPA/PAI-1 testing in daily clinical setting were calculated and individual reasons for decision making analyzed. Results: Among n=93 uPA/PAI-1 tests evaluated n=42/93 (45.2%) were uPA+PAI-1 negative and n=51/93 (54.8%) uPA and/or PAI-1 positive. In the group of uPA+PAI-1 negative test result in n=35/42 (83.3%) CTX was avoided and and in n=7/42 (16.7%) CTX performed. In the group of uPA and/or PAI-1 positive test result in n=26/51 (51.0%) CTX was performed and in n=25/51 (49.0%) not. Concordance of uPA/PAI-1 test result vs. consecutive therapy was (35+26)/93=65.6% and discordance of uPA/PAI-1 test-therapy (7+25)/93 = 34.4%. However, discordance of uPA/PAI-1 test result vs. Tumor Board recommendation was only n=21/93 (22.6%). As reasons for discordance a variety of influencing and/or interference factors were indentified, affecting use of test and test results or even changing therapy decision, e.g. individual therapy decision by physician, parallel use of competitive biomarkers, study participation, missing CTX therapy option in advance (like advanced age), wrong target group, timing of uPA/PAI-1 test too early, test result in contradiction of physicians' expectations (expected negative result) and rejection of CTX recommended by patients despite uPA/PAI-1 test-proven benefit. Conclusions: Individual process optimization of uPA/PAI-1 test indication, performance and result assessment could improve quality of care, reduce costs and lead to an improved application of uPA/PAI-1 test results as well as more stringency and consistency of test-therapy decisions in daily clinical setting. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-14-06.
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- 2012
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41. The Membership Problem for finitely generated quadratic modules in the univariate case
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Doris Augustin
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Combinatorics ,Discrete mathematics ,Semialgebraic set ,Polynomial ,Quadratic equation ,Algebra and Number Theory ,Bounded function ,Boundary (topology) ,Order (group theory) ,Isotropic quadratic form ,Element (category theory) ,Mathematics - Abstract
We prove that the Membership Problem is solvable affirmatively for every finitely generated quadratic module Q of R[X1]. For the case that the associated semialgebraic set S is bounded we show that a polynomial f is an element of Q if and only if f is nonnegative on S and fulfills certain order conditions in the boundary points of S. This leads us to the definition of generalized natural generators of the quadratic module Q.
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- 2012
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42. 30 Jahre Österreichische Gesellschaft für Senologie
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Tony Ng, Ulrike Freitag, Goran Azanjac, Martin Radespiel-Tröger, Anton Scharl, Volkan Kaynarog lu, Christoph Thomssen, Marion Kiechle, Sybille Loibl, Gabriele Klühs, Viktoria Aivazova-Fuchs, Ulrike Braisch, Karla Geiss, Dragan Čanović, Christine Mau, Philip Hepp, Julia Jückstock, Alexandra Schönherr, Derya Karakoc, Wolfgang Janni, W. Simon, Ali Konan, Fabrice Andre, Martin Meyer, Jasmina Nedovic, Michael Untch, Sherene Loi, Carmen Criscitiello, Ulrich Andergassen, Giuseppe Curigliano, Sheeba Irshad, İsmail Doğan, A Wischnik, Cristina Pirvulescu, Sedat Kiraz, Andrew Tutt, Klaus Friese, Ali Akdogan, Katherine Lawler, Brigitte Rack, Doris Augustin, Milan Knezevic, Nadia Harbeck, Katja Annecke, Barbara Fleige, J. Salmen, Demirali Onat, Umut Kalyoncu, Srdjan Ninkovic, Yusuf Alper Kilic, Davide Serrano, Holger Schultz, Slobodanka Mitrovic, Matteo Lazzeroni, Peter Dubsky, John Stagg, Thomas Zwingers, Nadja Harbeck, Dragce Radovanovic, Annette Isbruch, Heike Renner-Lützkendorf, Anita Grigoriadis, Nikolaos S. Salemis, Svjetlana Mohrmann, and Antje Sperfeld
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Oncology ,business.industry ,Medicine ,Surgery ,business ,Humanities - Published
- 2012
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43. Toxicity Analysis in the ADEBAR Trial: Sequential Anthracycline-Taxane Therapy Compared with FEC120 for the Adjuvant Treatment of High-Risk Breast Cancer
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A Wischnik, Viktoria Aivazova-Fuchs, Svjetlana Mohrmann, Julia Jückstock, Philip Hepp, Brigitte Rack, Thomas Zwingers, Alexandra Schönherr, Wolfgang Janni, W. Simon, J. Salmen, Klaus Friese, Doris Augustin, Nadia Harbeck, Ulrich Andergassen, Marion Kiechle, and Katja Annecke
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medicine.medical_specialty ,Taxane ,Cyclophosphamide ,Anthracycline ,business.industry ,Breast cancer ,Toxicity ,ADEBAR trial ,medicine.disease ,Gastroenterology ,ddc ,Surgery ,Original Article • Originalarbeit ,Regimen ,Oncology ,Docetaxel ,Internal medicine ,Medicine ,business ,Febrile neutropenia ,medicine.drug ,Epirubicin - Abstract
Data from meta-analyses have shown taxane-containing therapies to be superior to anthracycline-based treatments for high-risk breast cancer.The ADEBAR trial was a multicenter phase III trial in which patients with lymph node-positive breast cancer were prospectively randomized for either sequential anthracycline-taxane or FEC120 therapy. Patients received 4× epirubicin (90 mg/m(2)) and cyclophosphamide (600 mg/m(2)) every 3 weeks (q3w), followed by 4× docetaxel (100 mg/m(2)) q3w (EC-Doc arm), or 6× epirubicin (60 mg/m(2)) and 5-fluorouracil (500 mg/m(2)) on days 1 and 8 and cyclophosphamide (75 mg/m(2)) on days 1-14, q4w (FEC arm). We compared both arms with respect to toxicity and feasibility.Hematological toxicity was found significantly more often in the FEC arm. Febrile neutropenia was seen in 11.3% of patients in the FEC arm and in 8.4% of patients in the EC-Doc arm (p = 0.027). Non-hematological side effects of grade 3/4 were rarely seen in either arm. Therapy was terminated due to toxicity in 3.7% of the patients in the EC-Doc arm and in 8.0% of the patients in the FEC arm (p = 0.0009).The sequential anthracycline-taxane regimen is a well-tolerated and feasible alternative to FEC120 therapy.Metaanalysen zeigten die Überlegenheit von taxanhaltigen Chemotherapien gegenüber rein anthrazyklinbasierten Therapieregimen bei Hochrisiko-Mammakarzinompatientinnen.Die ADEBAR-Studie, als multizentrische Phase-III-Studie, randomisierte nodalpositive Mammakarzinompatientinnen entweder in den sequentiellen Anthrazyklin-Taxan-Arm oder in den FEC120-Arm. Die Patientinnen erhielten 4× Epirubicin (90 mg/mHämatologische Toxizität fand sich signifikant häufiger im FEC-Arm. Febrile Neutropenie trat bei 11,3% der Patientinnen im FEC-Arm auf sowie bei 8,4% der Patientinnen im EC-Doc-Arm (p = 0,027). Schwere nicht-hämatologische Nebenwirkungen Grad 3/4 traten in beiden Armen selten auf. Aufgrund von Toxizitäten musste die Therapie bei 3,7% der Patientinnen im EC-Doc-Arm sowie bei 8,0% der Patientinnen im FEC-Arm abgebrochen werden (p = 0,0009).Das sequentielle Anthrazyklin-Taxan-Regime ist eine gut verträgliche Alternative zu FEC120.
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- 2012
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44. Abstract P2-09-05: Risk Group Selection in Primary Breast Cancer According to ASCO Recommended Biomarkers Onkotype DX and uPA/PAI-1: First Experience from Prospective Multicenter WSG Plan B Trial
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Nadia Harbeck, Ronald E. Kates, C. Thomssen, S Shak, Martina Vetter, Tom Degenhardt, Christoph Uleer, M Kusche, Stefan Paepke, M Warm, J. Dünnebacke, O Gluz, U. Nitz, Michael Untch, and Doris Augustin
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Gynecology ,Oncology ,Cancer Research ,medicine.medical_specialty ,Chemotherapy ,medicine.diagnostic_test ,business.industry ,medicine.medical_treatment ,Concordance ,Cancer ,medicine.disease ,Risk groups ,Internal medicine ,medicine ,Hormonal therapy ,Clinical significance ,Risk factor ,business ,Oncotype DX - Abstract
Background: Both the Oncotype DX multi-gene assay and invasion factors uPA/PAI-1 are guideline-recommended (ASCO, AGO) biomarkers for decision support regarding adjuvant chemotherapy in primary breast cancer (BC). Material and Methods: The West German Study Group (WSG) Plan B trial (planned n=2,448) is evaluating anthracyline-free adjuvant chemotherapy (6x TC) vs. standard 4xEC-4xDOC in HER2- negative BC with 0-3 positive lymph nodes, Oncotype DX is used as selection criterion where pts with RS> 11 are randomized to one of the two chemotherapy arms and pts with RS ≥11 treated with hormonal therapy alone. uPA/PAI-1 (both low vs. either/both high), measured by ELISA, is obtained as an optional risk factor. Results: By June 2010, 1064 patients had been randomized in Plan B (96 recruiting centers). In 153 patients (27 centers), uPA and PAI-1 had been measured; for 131 (84 N0, 47 N+) of these, Oncotype DX Recurrence Score® (RS) results were also available. When considered as continuous variables, RS was weakly positively correlated (Spearman's coefficient) with uPA (rs=0.18, p=0.04) and with PAI-1 (rs=0.23, p=0.01). When considered as risk categories/(Table 1), there was a weak concordance between RS and uPA/PAI-1, using either the standard RS cutoff points (18 and 30) or the TAILORx trial cutoff points (11 and 25). Table T: Association between RS and uPA/PAI-1 categories Assignment of high risk was most strongly concordant between uPA/PAI-1 and RS (RS > 25: 22/25 patients had high uPA/PAI-1; RS >30: 14/15 patients had high uPA/PAI-1). This high-risk concordance extends to N0 patients (RS>25: 17/19 N0 pts had high uPA/PAI-1; RS>30: 11/12 pts had high uPA/PAI-1). Discussion: For the first time, risk groups in primary breast cancer according to both Oncotype DX and uPA/PAI-1 have been compared. These preliminary data show that the high RS group seems highly concordant with the prospectively assessed invasion markers uPA/PAI-1. However, within low and intermediate RS, uPA/PAI-1 could still identify a substantial collective at risk; low uPA/PAI-1 could define a clinically relevant low-risk collective within risk groups that would be classified as “intermediate” according to the multigene assay Oncotype DX. Additional recruitment and outcome assessment of the ongoing multicenter WSG Plan B trial will address the clinical significance of these findings. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-09-05.
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- 2010
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45. Impact of PIK3CA mutation status on immune marker response and pCR in the WSG-ADAPT HER2+/HR+ phase II trial
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Cornelia Liedtke, Sanne de Haas, Anke Kleine-Tebbe, Wolfram Malter, Michael Braun, Bahriye Aktas, Ronald E. Kates, Helmut Forstbauer, Regula Deurloo, Matthias Christgen, Nadia Harbeck, J. Tio, Ulrike Nitz, Rachel Wuerstlein, Hans Kreipe, Oleg Gluz, Doris Augustin, Sherko Kümmel, Claudia Schumacher, and Jochem Potenberg
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Oncology ,Cancer Research ,medicine.medical_specialty ,business.industry ,Pik3ca mutation ,Medizin ,Endocrine therapy ,Immune system ,Trastuzumab ,Internal medicine ,medicine ,skin and connective tissue diseases ,business ,neoplasms ,medicine.drug - Abstract
572Background: The ADAPT HER2+/HR+ phase II trial (NCT01745965) compared for the first time 12 wks. neoadjuvant T-DM1 (+/- endocrine therapy (ET)) with trastuzumab (T)+ET; pCR (ypT0/is ypN0) was > ...
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- 2018
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46. SABCS: Neues zur Adjuvanz und Immuntherapie des Mammakarzinoms
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Christoph Thomssen, Lothar Müller, Diana Lüftner, Doris Augustin, Norbert Marschner, Michael Untch, Nadia Harbeck, Renate Haidinger, Susanne Briest, Eugen Ruckhäberle, Johannes Ettl, Volkmar Müller, Druck, and Rachel Wuerstlein
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Gynecology ,medicine.medical_specialty ,Oncology ,business.industry ,medicine ,Surgery ,business - Published
- 2018
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47. Quadratic modules in $R[[X]]$
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Doris Augustin and Manfred Knebusch
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Ring (mathematics) ,Pure mathematics ,Quadratic equation ,Formal power series ,Applied Mathematics ,General Mathematics ,Euclidean field ,Variable (mathematics) ,Mathematics - Abstract
We give a complete list of all quadratic modules and inclusions between them in the ring R[[X]] of formal power series in one variable X over a euclidean field R.
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- 2010
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48. Impact of guideline-based use of uPA/PAI-1 on patient outcome in intermediate-risk early breast cancer
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Tom Degenhardt, Rachel Wuerstlein, Theresa M. Kolben, M Burgmann, Nina Ditsch, Thomas Kolben, Nadia Harbeck, R. Armbrust, C. Goess, Doris Augustin, and R Kates
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0301 basic medicine ,Oncology ,Adult ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Estrogen receptor ,Breast Neoplasms ,Kaplan-Meier Estimate ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Plasminogen Activator Inhibitor 1 ,Biomarkers, Tumor ,Medicine ,Humans ,Early breast cancer ,Aged ,Neoplasm Staging ,Gynecology ,Aged, 80 and over ,Chemotherapy ,business.industry ,Guideline ,Middle Aged ,medicine.disease ,Prognosis ,Urokinase-Type Plasminogen Activator ,030104 developmental biology ,Treatment Outcome ,030220 oncology & carcinogenesis ,Upa pai 1 ,Cohort ,Female ,business ,Intermediate risk - Abstract
The purpose of this study was to evaluate the influence of guideline-based prospective use of uPA/PAI-1 on clinical outcome in an intermediate-risk cohort of breast cancer patients. We analyzed 381 consecutive primary breast cancer patients (2003-2011) at the breast center Ostbayern meeting the following criteria: M0/N0/estrogen receptor (ER)+/G2. Clinical-pathological data, uPA/PAI-1, and follow-up data were collected. Decisions for adjuvant chemotherapy were made upon consideration of prospectively measured uPA/PAI-1. Observed disease-free survival (DFS) and overall survival (OS) were calculated by Kaplan-Meier estimates. Using guideline-based analysis of uPA/PAI-1, treatment with adjuvant chemotherapy was avoided in 86.5 % of patients with low uPA/PAI-1, i.e., 38.8 % of the total patient collective. Median follow-up was 52.5 months. Five-year relapse-free survival in intermediate-risk patients (N0, G2) without chemotherapy was 99 %. Five-year overall survival including all causes of death was 95 %. By using uPA/PAI-1, adjuvant chemotherapy can be avoided in a major part of patients with intermediate-risk breast cancer. Nevertheless, DFS and OS of these patients at 5 years remain excellent. The potential, but hardly measurable, benefit of adjuvant chemotherapy has to be set in contrast with its associated side effects and increased morbidity. Patients with high uPA/PAI-1 show benefit from chemotherapy. In this subgroup, a very good OS was observed as well. These findings strongly support the use of uPA/PAI-1 together with clinic-pathological parameters as an evidence-based, clinically relevant and inexpensive decision tool in the routine of a breast center.
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- 2015
49. Final results from the prospective phase III WSG-ARA trial: impact of adjuvant darbepoetin alfa on event-free survival in early breast cancer
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Ronald E. Kates, J. Dünnebacke, O Gluz, U. Nitz, V Runde, Toralf Reimer, John Hackmann, N. Belzl, C. Oberhoff, Doris Augustin, Claudia Schumacher, I. Zuna, Nadia Harbeck, Christoph Uleer, and M. Warm
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medicine.medical_specialty ,Darbepoetin alfa ,Anemia ,medicine.medical_treatment ,Medizin ,Breast Neoplasms ,Gastroenterology ,Disease-Free Survival ,Breast cancer ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Erythropoietin ,Proportional Hazards Models ,Chemotherapy ,Surrogate endpoint ,business.industry ,Hematology ,Middle Aged ,medicine.disease ,Chemotherapy regimen ,Surgery ,Pulmonary embolism ,Treatment Outcome ,Oncology ,Chemotherapy, Adjuvant ,Lymphatic Metastasis ,Hematinics ,Female ,business ,Adjuvant ,medicine.drug - Abstract
Background: WSG-ARA plus trial evaluated the effect of adjuvant darbepoetin alfa (DA) on outcome in node positive primary breast cancer (BC). Patients and methods: One thousand two hundred thirty-four patients were randomized to chemotherapy either with DA (DA+; n = 615) or without DA (DA-; n = 619). DA (500\textgreekmg q3w) was started at hemoglobin (Hb) levels \15g/dl were reported in 0.8\% of cycles. QoL parameters did not significantly differ between arms. At 39 months, DA had no significant impact on EFS (DA+: 89.3\%, DA-: 87.5\%; Plog-rank = 0.55) or OS (DA+: 95.5\%, DA-: 95.4\%; Plog-rank = 0.77). Conclusions: DA treatment did not impact EFS or OS in routine adjuvant BC treatment. \copyright The Author 2013. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved.
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- 2013
50. Febrile Neutropenien (FN) und Infektionen unter adjuvanter Chemotherapie des Mammakarzinoms mit 6xTC vs. 4xEC-4xDoc: Toxizitätsdaten der WSG planB Studie
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Bahriye Aktas, Ronald E. Kates, Michael J. Clemens, R von Schumann, Daniel Hofmann, Andrea Stefek, Nadia Harbeck, Toralf Reimer, Doris Augustin, F Lorenz-Salehi, M Salem, U. Nitz, Petra Krabisch, A Pollmanns, Christoph Uleer, B Liedtke, and O Gluz
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- 2013
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