31. Deutscher Krebskongress KON ntelligente Konzepte in der Onkologie

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1 Oncol Res Treat 7(suppl ) VI (0) 7 S print online ISSN e-issn 96 6 e-isbn Formerly Band 7, Supplement, Februar 0 ABSTRACTS. Deutscher Krebskongress KON ntelligente Konzepte in der Onkologie Berlin, 9.. Februar 0 Herausgeber Michael Hallek, Köln S. Karger Medical and Scientific Publishers Basel. Freiburg. Paris. London. New York. Chennai. New Delhi. Bangkok. Beijing. Shanghai. Tokyo. Kuala Lumpur. Singapore. Sydney

2 Band 7, Supplement, Februar 0 Offizielles Organ von DGHO Deutsche Gesellschaft für Hämatologie und Medizinische Onkologie ÖGHO Österreichische Gesellschaft für Hämatologie & Medizinische Onkologie DFaG Deutsche Fatigue Gesellschaft AIO Arbeitsgemeinschaft Internistische Onkologie in der Deutschen Krebsgesellschaft e.v. Mitglied der Deutschen Krebsgesellschaft e.v. Editors Editor-in-Chief M. Hallek, Köln Associate Editors S. Al-Batran, Frankfurt/M. C. Berking, München C. Bokemeyer, Hamburg M. Borner, Bern T. Cerny, St. Gallen H. T. Eich, Münster A. Engert, Köln M. Fassnacht, München B. Groner, Frankfurt/M. V. Heinemann, München M. Hentrich, München R. D. Issels, München W. Janni, Ulm U. R. Kleeberg, Hamburg H. Lang, Mainz M. Moehler, Mainz M. Schuler, Essen R. Stupp, Zürich M. Theobald, Mainz R. Thomas, Köln U. Wedding, Jena J. A. Werner, Marburg Editorial Board P. Albers, Düsseldorf C. Bausewein, München L. Bergmann, Frankfurt/M. J. Boos, Münster P. Brossart, Bonn W. Budach, Düsseldorf R. Büttner, Bonn E. Dippel, Ludwigshafen A. Du Bois, Essen T. Fehm, Düsseldorf F. Geiser, Bonn N. Harbeck, München A. Heidenreich, Aachen U. Herrlinger, Bonn A. Hochhaus, Jena R.-D. Hofheinz, Mannheim F. Honecker, St. Gallen V. Jacobs, Salzburg K. Jordan, Halle U. Keilholz, Berlin J. P. Klussmann, Gießen H. Kölbl, Wien W. Kuhn, Bonn H.-J. Lenz, Los Angeles P. Mallmann, Köln H. Moch, Zürich K. Possinger, Berlin P. Reichardt, Bad Saarow S. Reske, Ulm I. Runnebaum, Jena P. Schöffski, Leuven C. Spitzweg, München I. Strohscheer, St. Peter-Ording S. Ugurel, Graz R. Voltz, Köln M. Weller, Zürich Editorial Office S. Karger GmbH Attn. Dr. Steffi Hentzelt P.O. Box D-7909 Freiburg Basel Freiburg Paris London New York Chennai New Delhi Bangkok Beijing Shanghai Tokyo Kuala Lumpur Singapore Sydney

3 Disclosure Statement XXX Imprint ISSN Print Edition: ISSN Online Edition: 96 6 Journal Homepage: Publication Data: Volume 7, 0 of Oncology Research and Treatment appears with issues. Copyright: 0 by S. Karger Verlag für Medizin und Naturwissenschaften GmbH, Freiburg (Germany). All rights reserved. No part of the journal may be reproduced in any form without the written permission of the publisher. This includes digitalisation and any further electronic computing, like saving, copying, printing or electronic transmission of digitalized material from this journal (online or offline). Authorization to photocopy items for internal or personal use of specific clients is granted by Karger. Photocopying: This journal has been registered with the Copyright Clearance Center (CCC), as indicated by the code appearing on the first page of each article. For readers in the US, this code signals consent for copying of articles for personal or internal use, or for the personal or internal use of specific clients, provided that the stated fee is paid per copy directly to Copyright Clearance Center Inc., Rosewood Drive, Danvers, MA 09 (USA) A copy of the first page of the article must accompany payment. Consent does not extend to copying for general distribution, for promotion, for creating new works, or for resale. In these cases, specific written permission must be obtained from the copyright owner, S. Karger GmbH, Wilhelmstraße 0A, Freiburg (Germany). Disclaimer: The statements and data contained in this publication are solely those of the individual authors and contributors and not of the publisher and the editor(s). The appearance of advertisements in the journal is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting form any ideas, methods, instructions or products referred to in the content or advertisements. Distribution and Subscription: Karger offers three types of subscription: Print Only, Online Only and the combined Print + Online. The basic annual subscription rate is the same for all three delivery forms; however, a fee for the combined print and online subscription is levied, and there is a postage and handling charge for Print Only and Print + Online. Subscriptions run for a full calendar year. Prices are given per volume. Print subscription: EUR 6. + postage and handling. Online subscription: EUR 6.. Combined (print + online) subscription:. + postage and handling. For customers in Germany: Please turn to your bookshop or to S. Karger Verlag für Medizin und Naturwissenschaften GmbH Wilhelmstr. 0A, Freiburg (Germany) Tel , Fax For customers in all other countries: Please contact your bookshop or S. Karger AG Allschwilerstr. 0, 009 Basel (Switzerland) Tel , Fax Advertising: Correspondence should be addressed to the publisher. S. Karger Verlag für Medizin und Naturwissenschaften GmbH Attn. Ellen Zimmermann (Head of Marketing) Price list No. of January, 0 is effective. V.i.S.d.P. (Person responsible according to the German Press Law): Sibylle Gross Bibliographic Services Biological Abstracts Current Contents/Clinical Medicine Excerpta Medica/EMBASE Medicus/MEDLINE Medical Documentation Service Reference Update Research Alert Science Citation SCISEARCH Database 0 S. Karger GmbH, Freiburg Fax Accessible online at:

4 Band 7, Supplement, Februar 0. Deutscher Krebskongress KON ntelligente Konzepte in der Onkologie Berlin, 9.. Februar 0 ABSTRACTS Herausgeber Michael Hallek, Köln Basel Freiburg Paris London New York Chennai New Delhi Bangkok Beijing Shanghai Tokyo Kuala Lumpur Singapore Sydney

5 Oncol Res Treat 0;7(suppl ):IV Programmkomitee Gutachter Albers, P. (Düsseldorf), Bartsch, H.H. (Freiburg), Baumann, F. (Köln), Becker, J. (Graz), Bergmann, L. (Frankfurt/M), Bokemeyer, C. (Hamburg), Bruns, J. (Berlin), Büttner, R. (Köln), Cursiefen, C. (Köln), Dietel, M. (Berlin), Dietz, A. (Leipzig), Domagk, K. (Hamburg), Dunst, J. (Lübeck), Eggert, A. (Berlin), Engers, R. (Düsseldorf), Enghofer, E. (Leverkusen), Fehm, T. (Düsseldorf), Feyer, P. (Berlin), Fietkau, R. (Erlangen), Graeven, U. (Mönchengladbach), Gschwend, J. (München), Gutzmer, R. (Hannover), Hallek, M. (Köln), Hartmann, J. (Kiel), Hasch, G. (Darmstadt), Hegewisch-Becker. (Hamburg), Helbig, U. (Berlin), Hochhaus, A. (Jena), Hölscher, A. (Köln), Hübner, J. (Berlin), Issels, R. (München), Jackisch, C. (Offenbach), Katalinic, A. (Lübeck), Kerschgens, C. (Berlin), Kleeberg, U. (Hamburg), Klinkhammer-Schalke, M. (Regensburg), Kohlhuber, F. (Bonn), Kotzerke, J. (Dresden), Krege, S. (Krefeld), Kusch, M. (Köln), Lang, H. (Mainz), Lordick, F. (Leipzig), Mallmann, P. (Köln), Meier, K. (Soltau), Nettekoven, G. (Bonn), Neugebauer, E. (Witten), Ortmann, O. (Regensburg), Paradies, K. (Hamburg), Pfaff, H. (Köln), Reif, K. (Bochum), Retz, M. (München), Riemann, J.F. (Ludwigshafen), Röcken, C. (Kiel), Rüffer, J.U. (Köln), Schadendorf, D. (Essen), Schirren, J. (Wiesbaden), Schlag, P. (Berlin), Schmidberger, H. (Mainz), Schmutzler, R. (Köln), Singer, S. (Mainz), Souchon, R. (Tübingen), Stadler, R. (Minden), Steiner, T. (Erfurt), Stummer, W. (Münster), Sturm, D. (Chemnitz), Thomas, M. (Heidelberg), Thomas, R. (Köln), van, Oorschot. (Würzburg), Voltz, R. (Köln), vom, Hagen, U. (Berlin), Wallwiener, D. (Tübingen), Walther, J. (Heidelberg), Walter, S. (Bonn), Weisse, I. (Stuttgart), Wiedenmann, B. (Berlin), Wiegel, T. (Ulm), Wiestler, O. (Heidelberg), Wittekind, C. (Leipzig), Wolf, J. (Köln), Zander, T. (Köln) Albers, P. (Düsseldorf), Albus, C. (Köln), Arnold, D. (Freiburg), Bahra, M. (Berlin), Bamberg, M. (Tübingen), Beckmann, M.W. (Erlangen), Benzing, T. (Köln), Berdel, W.E. (Münster), Berthold, F. (Köln), Beuth, J. (Köln), Biersack, H.J. (Bonn), Bloch, W. (Köln), Bokemeyer, C. (Hamburg), Bootz, F. (Bonn), Brossart, P. (Bonn), Brüning, J. (Köln), Budach, W. (Düsseldorf), Cornely, O. (Köln), Debatin, K.M. (Ulm), Deckert, M. (Köln), Domagk, K. (Stadt), Emons, G. (Göttingen), Engenhart-Cabillic, R. (Marburg), Engers, R. (Neuss), Feyer, P. (Berlin), Fietkau, R. (Erlangen), Frank, K. (Köln), Friedel, G. (Gerlingen), Gabbert, H. (Düsseldorf), Gathof, B. (Köln), Geiser, F. (Bonn), Graeven, U. (Mönchengladbach), Harbeck, N. (München), Hartmann, G. (Bonn), Hegewisch-Becker, S. (Hamburg), Hellmich, M. (Köln), Henne-Bruns, D. (Ulm), Herden, J. (Köln), Herschbach, P. (München), Hertenstein, B. (Bremen), Heukamp, L. (Köln), Höffken, K. (Jena), Hohenberger, W. (Erlangen), Hölscher, A. (Köln), Hopt, U.T. (Freiburg), Howaldt, H.P. (Gießen), Hübner, J. (Berlin), Jonat, W. (Kiel), Kalff, J. (Bonn), Keller, M. (Heidelberg), Kiechle, M. (München), Klaschik, E. (Alfter), Klingebiel, T. (Frankfurt/M.), Koch, U. (Hamburg), Kortmann, R.D. (Leipzig), Krieg, T. (Köln), Kuhn, W. (Bonn), Lang, H. (Mainz), Lehmacher, W. (Köln), Liekweg, A. (Köln), Lutz, M. (Saarbrücken), Maintz, D. (Köln), Mallmann, P. (Köln), Malter, W. (Köln), Meier, K. (Soltau), Meyer, H.J. (Berlin), Molls, M. (München), Müller, S. (Bonn), Perner, S. (Bonn), Possinger, K. (Egling), Radbruch, L. (Bonn), Reif, K. (Bochum), Reinacher-Schick, A. (Bochum), Riemann, J.F. (Ludwigshafen), Rödel, C. (Frankfurt/M.), Scheid, C. (Stadt), Scheulen, M. (Essen), Schild, H. (Bonn), Schirren, J. (Wiesbaden), Schlegel, U. (Bochum), Schmidt-Wolf, I. (Bonn), Schmoll, H.J. (Halle/S.), Schmutzler, R. (Köln), Schuler, M. (Essen), Schulz, R.J. (Köln), Schütte, W. (Halle/S.), Seehofer, D. (Berlin), Seufferlein, T. (Ulm), Sterner-Kock, A. (Köln), Stürzl, M. (Erlangen), Stuschke, M. (Essen), Tannapfel, A. (Bochum), Thiel, E. (Berlin), Thomas, R. (Köln), Trümper, L. (Göttingen), Ukena, D. (Bremen), Unger, C. (Freiburg), Vanhoefer, U. (Hamburg), Vatter, H. (Bonn), Voltz, R. (Köln), vom, Hagen, U. (Berlin), Wahl, G. (Bonn), Wahlers, T. (Köln), Wallwiener, D. (Tübingen), Weis, J. (Freiburg), Welt, A, (Essen), Wenz, F, (Mannheim), Wiestler, O, (Heidelberg), Wittekind, C, (Leipzig), Zander, T, (Köln) 0 S. Karger GmbH, Freiburg Fax Accessible online at:

6 Oncol Res Treat 0;7(suppl ):V Antiangiogenic or Antimetastatic Agents Biomarkers Breast Cancer Adjuvant Therapy 0 Breast Cancer Local-Regional Therapy Breast Cancer Metastatic Breast Cancer 7 Cancer Prevention Cell Cycle, Apoptosis, Angiogenesis Cell-Based Therapy Central Nervous System Tumors Clinical Trial Design 7 Developmental Therapeutics: Immunotherapy 9 Developmental Therapeutics: Molecular Therapeutics Economy Epidemiology Functional Imaging 8 Gastrointestinal (Colorectal) Cancer (including liver metastases) 9 Gastrointestinal (Noncolorectal) Cancer 0 Gastrointestinal Stromal Tumors 7 Genitourinary Cancer including Prostate Cancer 8 Gynecologic Cancer 6 Head and Neck Cancer 76 Health Services Research 79 Leukemia, Myelodysplasia, and Transplantation 8 Lung Cancer Adjuvant Therapy 86 Lung Cancer Local-Regional Therapy 86 Lung Cancer Metastatic Lung Cancer 87 Lymphoma and Plasma Cell Disorders 9 Miscellaneous 9 Molecular Pathology 9 Molecular Targets 96 Oncological Pharmacy 00 Paediatric Cancer 0 Palliative Care 0 Patient Care 0 Phase I Studies 0 Psychooncology 06 Quality-of-Life Management Radiation Biology 0 S. Karger GmbH, Freiburg Fax Accessible online at:

7 Oncol Res Treat 0;7(suppl ):VI Sarcoma Skin Cancer including Melanoma 8 Stem Cells in Cancer 9 Supportive Care 0 Surgical Oncology Tumor and Cell Biology 7 Tyrosine Kinase Inhibitors Pflegerische Beiträge Autorenindex Imprint II 0 S. Karger GmbH, Freiburg Fax Accessible online at:

8 Abstracts Oncol Res Treat 0;7(suppl ): Antiangiogenic or Antimetastatic Agents ID 8 Dimethylfumarate suppresses prostate cancer cell proliferation and fortifies chemotherapeutic action I. Hrgovic, E. Valesky, R. Rustemeyer, T. Hailemariam-Jahn, F. Roos, A. Pinter, R. Kaufmann, M. Meissner Universitätsklinik Frankfurt, Klinik für Dermatologie, Venerologie und Allergologie, Frankfurt, Universitätsklinik Mainz, Klinik für Urologie, Mainz, Recent evidence suggests, that Dimethylfumarate (DMF), known as a highly potent anti-psoriatic agent, might have anti-tumorigenic properties. To analyze, the effects of DMF on prostate carcinoma cell lines, we first performed cytotoxicity assays with the androgen dependent cell line LNCAP and the androgen independent cell line PC-. No LDH release could be demonstrated. In further analysis we could show, that DMF suppresses prostate carcinoma cell proliferation in a concentration dependent manner. These effect could be paralleled with reduced prostate specific antigen (PSA) expression. In functional tumor invasion assays we could demonstrate that DMF treatment reduces prostate cancer cell invasion almost as effective as the first-line chemotherapeutic Docetaxel. To examine whether these effects are conveyed by apoptotic mechanisms we performed apoptosis assays. There was no significant apoptosis induced by DMF in both cell lines. Therefore, we performed cell cycle analysis. DMF induced an G0/G arrest in both prostate carcinoma cell lines. Interestingly, in LNCAP DMF induced p, p and p7 whereas in PC-, which harbors a p mutation, only p and p7 were induced. In further experiments, possible additive effects of DMF treatment combined with Docetaxel, were evaluated. Here, it could be demonstrated, that the combination of both agents is more effective than the chemotherapeutic agent alone. These data provide first evidence, that DMF inhibits prostate cancer proliferation by reinduction of important cell cycle inhibitors. The combination of Docetaxel and DMF provides additive anti-cancer effects. Hence, DMF might be an interesting agent in the treatment of prostate cancer and is worth for further in vivo analysis. ID -Methoxyestradiol impairs lymphangiogenesis through G /M cell cycle arrest and apoptosis I. Hrgovic, M. Doll, A. Pinter, S. Kippenberger, E. Valesky, R. Kaufmann, M. Meissner Klinikum der Johann Wolfgang Goethe-Universität, Klinik für Dermatologie, Venerologie und Allergologie, Frankfurt am Main, Question: Lymphangiogenesis is a crucial step in the progression of cancer. Formation of new lymphatic vessels provides an additional route for tumor cells to metastasize. Therefore, inhibiting lymphangiogenesis represents an interesting target in cancer therapy. -Methoxyestradiol (-ME) is a physiological metabolite of estradiol with low cytotoxicity. As -ME promotes anti-angiogenic effects on endothelial cells, we hypothesized that -ME may have impact on lymphangiogenesis. Methods: Human lymphatic endothelial cells (LEC) were cultured in vitro and treated with or without -ME. Effects of -ME on proliferation, cell cycle progress and apoptosis were analyzed mainly by Bromdesoxyuridin assay, flow cytometry and immunoblotting. In vitro angiogenesis was investigated using the Matrigel tube formation assay. Results: We found that -ME inhibited cell proliferation in a concentration-dependent manner. Furthermore, we demonstrate that -ME induced both G/M arrest and apoptosis in LEC. Cell cycle arrest was accompanied by up-regulation of p and p, as well as down-regulation of Cyclin B, Cdcc and cdc. In addition, -ME induced apoptosis by cytochrome c release, activating Caspase-9, -7, and - and cleavage of poly-(adp-ribose) polymerase and up-regulation of the pro-apoptotic Protein Bim, whereas cleavage of Caspase 8 was unaffected by higher concentrations of -ME. Moreover, -ME induced in a time-dependent manner an activation of ERK/ and JNK in LEC. Inhibition of JNK- and ERK/-pathway reduced -ME-induced apoptosis of LEC. In further analysis, we could demonstrate an inhibition of the formation of capillary like structures by -ME treatment. Conclusion: Our results demonstrated that -ME has distinct anti-lymphangiogenic effects by arresting cell cycle in G/M phase and activating the intrinsic apoptotic pathway. ID 6 HDAC inhibitors decreases lymphangiogenesis by inducing apoptosis and cell cycle arrest via p/p-dependent pathways I. Hrgovic, M. Doll, A. Pinter, S. Kippenberger, E. Valesky, R. Kaufmann, M. Meissner Klinikum der Johann Wolfgang Goethe-Universität, Klinik für Dermatologie, Venerologie und Allergologie, Frankfurt am Main, Question: Lymphangiogenesis is a crucial step in the progression of cancer. Formation of new lymphatic vessels provides an additional route for tumor cells to metastasize. Therefore, inhibiting lymphangiogenesis represents an interesting target in cancer therapy. Recent evidence suggests that histone deacetylase inhibitors (HDACi) may mediate part of their antitumor effects by interfering with angiogenesis. We therefore examined the potential impact of three different HDACi, trichostatin A (TSA), sodium butyrate (NaB) and valproic acid (VPA) on cell proliferation in primary human lymphatic endothelial cells (LEC). Methods: Human lymphatic endothelial cells (LEC) were cultured in vitro and treated with or without HDACi. Effects of HDACi on proliferation, cell cycle progress and apoptosis were analyzed mainly by BrdU-Assay, flow cytometry and immunoblotting. Results: HDACi inhibited cell proliferation in a concentration-dependent manner. We found that TSA induced G0/G arrest in LEC. Cell cycle arrest was accompanied by up-regulation of p and p. Moreover, we found that p mrna was significantly up-regulated by TSA, while the protein and mrna half-life remains largely unaffected. The promoter activity of p was enhanced by TSA indicating a transcriptional mechanism. Subsequent EMSA analyses showed increased constitutive Sp/-dependent DNA binding in response to HDAC inhibition. We demonstrated that p was required for TSA induced p expression. Interestingly, sirna-mediated p depletion reduced the antiproliferative effects of TSA in LEC. In addition, TSA induced apoptosis by cytochrome c release, activating Caspase-9/-7 and down-regulating the anti-apoptotic proteins ciap-/-. Conclusion: In conclusion, we demonstrate that HDACi have distinct anti-lymphangiogenic effects by activating the intrinsic apoptotic pathway and cell cycle arrest via p/p-dependent pathways. 0 S. Karger GmbH, Freiburg Fax Accessible online at:

9 Biomarkers ID 07 Osteopontin, vascular endothelial growth factor and carbonic anhydrase 9 as potential biomarkers in the radiochemotherapy of non small-cell lung cancer C. Ostheimer, M. Bache, A. Güttler, M. Kotzsch, D. Vordermark Martin-Luther-Universität Halle-Wittenberg, Klinik für Strahlentherapie, Halle, Technische Universität Dresden, Institut für Pathologie, Dresden, Background: Prognosis and therapeutic outcome of advanced stage non small-cell lung cancer (NSCLC) remains poor and combined radiochemotherapy often is the definite treatment. However, hypoxic radioresistance limits the response to radiotherapy. This prospective study evaluated the inter-relationship and prognostic quality of hypoxia-related proteins in NSCLC patients treated by radiochemotherapy. Material and Methods: Pre-treatment osteopontin (OPN), vascular endothelial growth factor (VEGF) and carbonic anhydrase 9 (CA 9) plasma levels were determined by ELISA in NSCLC (M0) patients. Treatment consisted of a 66-Gy curative-intended radiotherapy ± chemotherapy. Biomarker correlation, association with clinicopathological parameters and the prognostic value of a biomarker combination was assessed. Results: All biomarkers linearly correlated and were linked to different clinical parameters including weight loss (OPN), gross tumor volume (VEGF) and T stage (CA 9). Single marker plasma levels of OPN (p = 0.0), VEGF (p = 0.0) and CA 9 (p = 0.0) significantly predicted overall survival. Biomarker combination correlated additively with prognosis and increased the risk of death by a factor. The effect was most pronounced with the triple combination OPN/VEGF/CA 9, yielding a 6-fold risk of death (p = 0.009). Combined plasma levels of OPN/VEGF/CA 9 were independent predictors of survival in a multivariate analysis (p = 0.0). Conclusions: These results suggest that a biomarker co-detection augments the prognostic value of single markers. The studied proteins should be considered for a hypoxic biomarker profile which might help identifying patients with hypoxic and radioresistant tumors. ID 00 Comparison of the prognostic significance of immunoglobulin kappa C, CD and CD8 in node-negative breast cancer M. Schmidt, B. Hellwig, I. Sicking,, M. Battista, S. Gebhard, A. Lebrecht, M. Gehrmann, R. Wirtz,, G. Hoffmann, C. Solbach, J. Rahnenführer,, J. Hengstler,, Universitätsmedizin Mainz, Frauenklinik, Mainz, Technische Universität, Institut für Statistik, Dortmund, Bayer GmbH, Leverkusen, Stratifyer, Köln, Technische Universität, Leibniz Research Centre for Working Environment and Human Factors (IfADo), Dortmund, Background: The prognostic significance of tumor-infiltrating lymphocytes in breast cancer is well accepted. We compared the prognostic relevance of immunoglobulin kappa C (IGKC), CD and CD8 in node-negative breast cancer using mrna expression. Methods: Microarray based gene-expression data for IGKC (669_x_ at), CD (07_at) and CD8 (078_at) were analyzed in four previously published cohorts (Mainz, Rotterdam, Transbig, Yu) of node-negative breast cancer patients not treated with adjuvant therapy (n = 8). The prognostic significance for metastasis-free survival (MFS) was compared using a likelihood-ratio-test in the whole cohort as well as in different molecular subtypes (luminal A, luminal B, basal-like, HER+). Results: IGKC (p < 0.00) had the strongest independent association with MFS in the whole cohort of node-negative breast cancer patients. CD (p < 0.0) and CD8 (p < 0.0) showed only a significant association with MFS in univariate analysis. In luminal A breast cancer, neither IGKC nor CD nor CD8 were associated with MFS. In luminal B tumors, only IGKC retained independent prognostic significance (p < 0.00). IGKC showed univariate significance in basal-like breast cancer (p < 0.0) and retained the significance when included in the model as second variable after CD. In HER+ breast cancer, IGKC (p < 0.00) as well as CD (p < 0.0) and CD8 (p < 0.0) displayed univariate significance but only IGKC maintained independent relevance (p < 0.0). Conclusion: IGKC as marker of the humoral immune system showed the strongest association with MFS in node-negative breast cancer as compared to CD or CD8. There were marked differences in the prognostic relevance between different molecular breast cancer subtypes. ID 079 Immunological parameters as predictive and prognostic biomarkers for chemoradioimmunotherapy of patients with pancreatic adenocarcinoma A. Bazhin, J. Werner, S. Karakhanova Chirurgische Uniklinik Heidelberg, Heidelberg, Pancreatic adenocarcinoma (PDAC) has a particularly poor prognosis with a median survival of 6 months. Nowadays the standard treatment today is surgical resection and subsequent adjuvant chemotherapy. This is possible in about 0% of all patients, and results in a median survival of over 0 months. Chemoradioimmunotherapy of patients with pancreatic adenocarcinoma (CapRitrial) did not show benefit of interferon-α adding to -fluorouracil based treatment protocol. However, the clinical outcome represented the best ever reported survival for patients with resected pancreatic cancer in adjuvant setting. The aim of the present work was to identify immunological parameters in a group of patients treated with chemoradioimmunotherapy, which could be useful for predictive and/ or prognostic purpose.here we provide evidence that high lymphocyte number before the therapy correlates positive with better disease-free and overall survivals. An increase in effector cytotoxic T cells or a high increase in effector memory CD8 + T cells after interferon-α injection have a positive correlation with the patients outcome during the therapy. Moreover a decrease in CD cells expressing immunosuppressive molecule CD is associated with better disease-free survival. Thus, tmmunological parameters, identified in this trial as possible surrogate blood markers, may be of interest and importance in context of the personalized medicine for improvement of PDAC patients treatment, after a validation in a prospective setting. ID 08 WTZ-Tumorprofil A preemptive biomarker profiling program in relation to personalized clinical drug development at a large German Comprehensive Cancer Center: Two years experience. M. Wiesweg, S. Ting, H. Reis, K. Worm, S. Kasper, S. Bauer, T.C. Gauler, A. Welt, H. Richly, M. Tewes, J. Meiler, J. Hense, W.E. Eberhardt, C. Derks, D. Cortes-Incio, S. Skottky, J. Wohlschläger, F. Breitenbücher, L. Freitag, G. Stamatis, K.W. Schmid, M. Schuler, Universität Duisburg-Essen, Westdeutsches Tumorzentrum, Innere Klinik (Tumorforschung), Essen, Universität Duisburg-Essen, Westdeutsches Tumorzentrum, Institut für Pathologie und Neuropathologie, Essen, Universität Duisburg-Essen, Westdeutsches Lungenzentrum, Ruhrlandklinik, Essen, Background: Biomarker-guided treatment of metastatic lung cancer, GIST or melanoma has set unprecedented examples for effective targeted therapies. Multiple investigational drugs are explored in patient populations defined by specific biomarkers of low prevalence, demanding a novel process of patient identification for early clinical trials. Here we Oncol Res Treat 0;7(suppl ): Abstracts

10 describe a biomarker program linked to the standard diagnostic algorithm which has been initiated at the West German Cancer Center, one of German Oncology Centers of Excellence. Methods: In addition to standard diagnostic procedures, profiling is offered to all patients with advanced lung or colorectal cancer, who meet generic study inclusion criteria. Biomarkers comprise oncogenic driver mutations (KRAS, NRAS, EGFR, BRAF, PIKCA, DDR), gene amplifications and translocations (HER, ALK, FGFR, PIKCA, ROS), and PTEN loss, following prespecified algorithms. The clinical course of profiled patients is closely monitored offering trial participation whenever applicable. Results: 0 patients (0 NSCLC, 09 CRC) have been profiled in 0 months. The most prevalent biomarkers were KRAS mutations (9%) for adeno NSCLC, FGFR amplification (%) for squamous NSCLC, and KRAS (8%) and BRAF (6%) mutations for CRC. patients have entered biomarker-guided clinical trials, while therapeutic decisions for approved drugs were guided in 68 patients. Conclusion: Preemptive biomarker profiling was established as part of the diagnostic algorithm of a large Comprehensive Cancer Center, enabling the prospective identification of patients eligible for biomarker-guided trials. High patient numbers and substantial investments are mandatory. ID 09 The detection of excision repair cross-complementing rodent repair deficiency, complementation group -positive circulating tumor cells in the blood of ovarian cancer patients as a predictive biomarker for platinum-resistance J.D. Kuhlmann, P. Wimberger, A. Bankfalvi, T. Keller, S. Schöler, B. Aktas, P. Buderath, S. Hauch, R. Kimmig, S. Kasimir-Bauer Universitätsklinikum Dresden, Klinik für Frauenheilkunde und Geburtshilfe, Dresden, Universitätsklinikum Essen, Institut für Pathologie und Neuropathologie, Essen, Acomed Statistics, Leipzig, Universitätsklinikum Essen, Klinik für Frauenheilkunde und Geburtshilfe, Essen, Adnagen AG, Langenhagen, Platinum-resistance constitutes one of the most recognized clinical challenges for ovarian cancer. Primary tumor-based ERCC-detection by immunhistochemistry was recently shown to be inaccurate for the prediction of platinum-resistance. Considering our previous finding that circulating tumor cells (CTC) in the blood of ovarian cancer patients are prognostically significant and hypothesizing that negative prognostic impact of CTC may arise from a cellular phenotype, being associated with platinum-resistance, we now inquired, whether ERCC-expression in CTC may be a suitable biomarker for stratifying response to platinum-based chemotherapy. In total, patients were studied. The presence of CTC was analyzed by immunomagnetic CTC-enrichment, targeting the epithelial epitopes GA 7. (EpCAM) and MUC-, followed by multiplex RT-PCR to detect the transcripts GA7- (EpCAM), MUC- and Ca, including ERCC in a separate approach. ERCC-expression in the primary tumor was assessed by immunhistochemistry (antibody 8F). At primary diagnosis ERCC + CTC were observed in 8% of patients and associated with decreased progression-free survival (PFS) and overall survival (OS) (p = 0.07, p = 0.0, respectively). Moreover, multivariate analysis revealed ERCC + CTC to be an independent predictor for a poor PFS (p = 0.007). Most interestingly, the presence of ERCC + CTC at primary diagnosis was an independent predictor for platinum-resistance (p < 0.007), whereas ERCC-expression in corresponding primary tumor tissue predicted neither platinum-resistance, nor prognosis. This is the first report, suggesting a blood-based assay for predicting platinum-resistance at primary diagnosis of ovarian cancer. ID 099 Validation of plasma proneurotensin as a novel biomarker for the prediction of incident breast cancer O. Melander, M. Belting, P. Almgren, J. Manjer, B. Hedblad, G. Engström, J. Struck, U. Kilger, P. Nilsson, A. Bergmann, M. Orho-Melander Skåne University Hospital, Malm, Clinical Research Center, Ent 7, bldg 9, floor, Malmö, Schweden Lund University, Section of Oncology, Lund, Schweden Sphingotec GmbH, Hennigsdorf, Context: Experimental settings have indicated that Neurotensin regulates both satiety and breast cancer growth. In a first study (Malmö Diet and Cancer Study) increasing fasting plasma Proneurotensin -7, a stable peptide derived from the same precursor as Neurotensin, was significantly associated with the development of breast cancer. Objective: To validate in an independent second study the initial finding of proneurotensin being a risk prediction marker for the development of breast cancer. Design, Setting, and Participants: The Malmö Preventive Project (MPP) is a general population study and comprised 8,00 subjects at the timepoint of first re-examination (00 006). Of these subjects 69 women including all women of the entire re-examination cohort who developed breast cancer until 0 were randomly selected for baseline plasma proneurotensin assessment. The mean age of the women at baseline was 70.0±. years, and all women were free from breast cancer at baseline. Proneurotensin was measured in samples from these fasting women and related to the risk of later breast cancer development, which had occurred until 0 (0 incident breast cancer events), using multivariate Cox proportional hazards models. Results: In the women of the MPP study, Proneurotensin (hazard ratio [HR] per SD increment of log-transformed proneurotensin) was related to incident breast cancer (0 events; HR,.07; 9% CI,.77.; P <.00; adjusted for age, BMI and smoking). This Hazard ratio was even stronger than initially observed in the Malmö Diet and Cancer Study ( events; HR,.; 9% CI,..7; P <.00). The women investigated in the MPP study were about 0 years (mean) older than in the Malmö Diet and Cancer Study. Conclusion: Proneurotensin has been validated in a second cohort as a novel risk stratification marker for the development of breast cancer. ID 00 A biomarker based detection and characterization of carcinomas exploiting two fundamental biophysical mechanisms in mammalian cells M. Grimm, P. Teriete, S. Schmitt, T. Biegner, A. Stenzl, J. Hennenlotter, H.-J. Muhs 6, A. Munz, T. Nadtotschi, K. König 7, J. Sänger 8, O. Feyen 9, H. Hofmann 9, S. Reinert, J.F. Coy 9 University Hospital Tuebingen, Department of Oral and Maxillofacial Surgery, Tuebingen, Cancer Research Center, Sanford-Burnham Medical Research Institute, La Jolla, CA, USA, Vereinigte Staaten von Amerika University Hospital Heidelberg, German Cancer Research Center (DKFZ) Flow Cytometry Core Facility, Heidelberg, University Hospital Tuebingen, Department of Pathology, Tuebingen, University Hospital Tuebingen, Department of Urology, Tuebingen, 6 Clemenshospital Muenster, Department of Gynecology, Muenster, 7 University Hospital Tuebingen, Department of Anaesthesiology and Intensive Care Medicine, Tuebingen, 8 Institute of Pathology, Bad Berka, 9 TAVARLIN AG, Pfungstadt, Background: Biomarkers allowing the characterization of malignancy and therapy response of oral squamous cell carcinomas (OSCC) or other types of carcinomas are still outstanding. The biochemical suicide mole- Abstracts Oncol Res Treat 0;7(suppl ):

11 cule endonuclease DNaseX (DNaseI-like ) has been used to identify the Apo0 protein epitope that marks tumour cells with abnormal apoptosis and proliferation. The transketolase-like protein (TKTL) represents the enzymatic basis for an anaerobic glucose metabolism even in the presence of oxygen (aerobic glycolysis/warburg effect), which is concomitant with a more malignant phenotype due to invasive growth/metastasis and resistance to radical and apoptosis inducing therapies. Methods: Expression of Apo0 and TKTL was analysed retrospectively in OSCC specimen (n = 6) by immunohistochemistry. Both markers represent independent markers for poor survival. Furthermore Apo0 and TKTL have been used prospectively EDIM-blood test in patients with OSCC (n = 0), breast cancer (n = 8), prostate cancer (n = ), and blood donors/controls (n = 7). Results: Positive Apo0 and TKTL expression were associated with recurrence of the tumor. Multivariate analysis demonstrated Apo0 and TKTL expression as an independent prognostic factor for reduced tumor-specific survival. Apo0+/TKTL+ subgroup showed the worst disease-free survival rate in OSCC. EDIM-Apo0 and EDIM-TKTL blood tests allowed a sensitive and specific detection of patients with OSCC, breast cancer and prostate cancer before surgery and in after care. A combined score of Apo0+/TKTL+ led to a sensitivity of 9.8% and a specificity of 97.% for the detection of carcinomas independent of the tumor entity. Conclusions: The combined detection of two independent fundamental biophysical processes by the two biomarkers Apo0 and TKTL allow a sensitive and specific detection of neoplasia in a noninvasive and cost-effective way. ID 0 Plasma Pro-Enkephalin, a stable peptide of the precursor to the endogenous opioid Enkephalin, predicts breast cancer risk O. Melander, M. Orho-Melander, P. Almgren, J. Manjer, B. Hedblad, G. Engström, J. Struck, P. Nilsson, A. Bergmann, M. Belting Skåne University Hospital, Malm, Clinical Research Center, Ent 7, bldg 9, floor, Malmö, Schweden Sphingotec GmbH, Hennigsdorf, Context: Opioid peptides may negatively regulate carcinogenesis and the growth of breast tumors by various mechanisms. Little is known about their role in the development of breast cancer in humans. Pro-Enkephalin A 9-9 (pro-enk), a peptide derived from the same precursor as Enkephalin, has been developed as a reliable surrogate plasma marker for the unstable Enkephalin. Objective: To test if fasting plasma levels of pro-enk are associated with development of incident breast cancer. Design, Setting, and Participants: We measured pro-enk in fasting plasma from women (mean age 8±.9 years) of the population based Malmö Diet and Cancer Study (MDCS) free from breast cancer prior to the baseline exam in pro-enk was related to first breast cancer events (n = ) during a median of.8 years of follow-up. For replication, we related pro-enk to risk of later breast cancer development (0 incident events) in an independent sample from the Malmö Preventive Project (MPP) consisting of 69 women (mean age 70.0±. years), all free from breast cancer at baseline. Results: In the MDCS, pro-enk was inversely related to risk of incident breast cancer [HR 0.76 ( ), P = 0.00)]. Women belonging to quartiles, and compared to women belonging to the th quartile of plasma pro-enk had hazard ratios of. (0.7.0),.0 (..) and.8 (.6.) (P < 0.00). In the MPP, the odds ratio was 0.6 (0. 0.7) (P<0.00). As compared to women belonging to the th quartile of plasma pro-enk, women belonging to quartiles, and had odds ratios for breast cancer of. (..88),.9 (.9.7) and.79 (. 9.) (P<0.00). Conclusion: In two large general population studies low fasting plasma concentration of pro-enk is strongly associated with increased risk of future breast cancer development in middle aged and post-menopausal women. ID 6 Specific mirna signatures characterize distant metastases of clear cell renal cell carcinoma at different sites J. Heinzelmann,, U. Wickmann, S. Baumgart,, F. Stolzenbach, R. Schneeweiss, M. Gajda, M. Stöckle, K. Junker Universitätsklinikum des Saarlandes, Klinik für Urologie, Homburg, Universitätsklinikum Jena, Klinik für Urologie, Jena, Universitätsklinikum Jena, Institut für Pathologie, Jena, Background: mirnas are regulators of gene expression in tumorigenesis and progression. To identify mirnas associated with metastases mir- NA expression in distant metastases was compared to primary ccrcc. Material and Methods: Total RNA of 7 primary ccrcc samples and distant metastases (lung, bone and brain) was isolated from formalin-fixed paraffin-embedded (FFPE) samples Microarray analyses were performed for a global mirna expression profiling. Results were validated by qpcr. Results: We identified 9 mirnas (including mir-0c and mir-6) with a similar expression in metastatic primary ccrcc and distant metastases from different metastatic sites compared to non-metastatic primary ccrcc. mirnas (including mir-0b and mir-0) were differently expressed in distant metastases compared to primary ccrcc. Furthermore, each metastatic site is characterized by a specific mirna signature. Results were verified on selected mirnas using qpcr. Ongoing in vitro studies are investigating the functional role of mirnas in metastatic processes of ccrcc. Discussion: These data suggest that mirnas play an important role in metastatic processes of ccrcc. Furthermore, our results regarding different metastatic sites suggest to two important statements: Specific mirnas characterize distant metastases in general. On the other hand, mirna expression is associated with specific conditions at different metastatic sites. Thus, the data presented in this study give the base for a better understanding of the involvement of mirnas as regulators of metastasis which opens new possibilities for new targeted therapy options. ID 77 A new diagnostic test for monitoring of breast cancer patients A.-R. Rotmann Praxis für Gynäkologie, Rodgau-Nieder-Roden, Background: Impaired glucose metabolism and elevated blood glucose levels have been linked with increased cancer risk and cancer mortality. New therapies have been established addressing new targets controlling glucose metabolism in breast cancer patients. Recently it has been shown that the detection of the biomarker transketolase-like- (TKTL) in monocytes allows the detection of upregulated glucose metabolism in cancer patients. The epitope detection in monocytes (EDIM) has been established as a new technology for a non-invasive biomarker based detection and characterization of tumors as well as early detection of recurrence and/or metastasis. The biomarker Apo0 is highly specifically expressed in tumor cells irrespective of the tumor entity and is accumulated in due to blocked apoptosis. Thus, the combined use of the biomarkers Apo0 and TKTL offers the possibility to detect abnormal cell proliferation and up-regulated glucose metabolism, indicating neoplasias and the degree of malignancy. This new technology also could be used to identify breast cancer patients that will benefit from existing and new therapeutic approaches. Just re- Oncol Res Treat 0;7(suppl ): Abstracts

12 cently the mtor inhibitor everolimus has been approved and Metformin has been shown to reduce the incidence of invasive breast cancer. Methods: In a routine gynecological practice we use the test for early detection, for monitoring of patients during treatment and in aftercare. Conclusion: Our data from more than 00 patients with breast cancer for a period up to years are promising results worth to be further validated. This new diagnostic test could be a useful tool to identify and monitor cancer patients and the use of new therapies. ID 8 Expression of progesterone receptor membrane component (PGRMC) in tissues of breast cancer patients I. Wurster, C. Meisner, H. Seeger, U. Vogel, H. Schneck, C. Blassl, S. Schultz, T. Fehm, H. Neubauer University of Tuebingen, Institute for Clinical Epidemiology and Applied Biometry, Tuebingen, University of Tuebingen, Department of Obstetrics and Gynaecology, Tuebingen, University of Tuebingen, Institute of Pathology, Tuebingen, Heinrich Heine University of Duesseldorf, Department of Obstetrics and Gynaecology, Duesseldorf, Objectives: Progesterone receptor membrane component (PGRMC) may be important in tumorigenesis and may thus increase the risk for developing breast cancer under certain circumstances e.g. during hormone therapy. The main purpose of this study was to investigate the expression of PGRMC in benign and malignant tissues of breast cancer patients. Methods: Matching baseline tissue biopsies of 69 breast cancer patients undergoing pre-surgery therapy were analyzed by immunohistochemistry for expression levels of PGRMC and its phosphorylated version at serine 80 (ppgrmc). Associations with clinicopathological parameters, e.g. tumour grading and receptor expression, and patient s characteristics such as the patient s age were calculated. Results: PGRMC and ppgrmc are expressed in breast cancer tissue as well as in connective tissue and are co-expressed with estrogen receptors, but not with progesterone receptor. Every breats cancer specimen showed expression of PGRMC and ppgrmc with a very strong expression in the cytoplasm of tumour cells. A much weaker signal was detected in connective tissue surrounding the actual carcinoma tissue (p < 0.00). No correlation was observed forthe expression of PGRMC and ppgrmc with histopathological status, menopausal status, tumour grading or the patient s age. However, the expression of PGRMC and ppgrmc appears to be correlated with the expression of certain hormone receptors, especially in the age group of years. Stratification for age revealed that ppgrmc is significantly higher expressed in elderly patients > 70 years than in the age groups 0 9 and years. Conclusion: PGRMC is highly expressed in breast tumour tissues and thus may play a decisive role in breast cancer development. Further studies are necessary to reveal how PGRMC may be involved in breast carcinogenesis probably triggered by hormone therapy. ID 8 Medroxyprogesterone acetate-driven increase in breast cancer risk might be mediated via cross-talk with growth factors in the presence of progesterone receptor membrane component- H. Neubauer, H. Seeger, H. Schneck, A. Mueck, T. Fehm Heinrich Heine University of Duesseldorf, Department of Obstetrics and Gynaecology, Duesseldorf, University of Tuebingen, Department of Obstetrics and Gynaecology, Tuebingen, Background: The WHI trial suggests an increase of breast cancer in postmenopausal women probably according to the progestogenic compound, i.e. medroxyprogesterone acetate (MPA). However, the mechanism for a possible carcinogenic effect of MPA remains unclear so far. Progesterone receptor membrane component- (PGRMC) may be important in tumorigenesis and thus may increase breast cancer risk. We investigated the influence of MPA alone and in combination with growth factors on breast cancer cells overexpressing PGRMC. Methods: MCF-7 cells were stably transfected with PGRMC expression plasmid (WT- cells). Cells transfected only with the vector were used as control cells (EVC-cells). Medroxyprogesterone acetate (MPA), norethisterone (NET) and progesterone (P) were tested alone and in combination with a mixture of growth factors. Cell proliferation was measured by MTT assay. Results: The growth factor mixture (GF) was able to induce cell proliferation in both cell types, however, the effect was much higher in the WT- cells. In WT- cells both MPA and NET alone significantly increased cell proliferation with values of 0% and 97%, respectively. Progesterone, however, had no effect. In combination with GF MPA significantly further enhanced cell proliferation as compared to the effect of MPA alone and GF alone in both cell lines. NET showed no further increase as compared to NET alone and P had no effect. Conclusions: We could demonstrate a significant proliferative effect of MPA when combined with high concentrations of growth factors. This effect was more pronounced in breast cancer cells overexpressing PGRMC. These results may be of clinical relevance since in the combined WHI trial an increased breast cancer risk was found during treatment with conjugated equine estrogens plus MPA. ID 90 Analysing the mutational status of PIKCA in circulating tumor cells from metastatic breast cancer patients F. Meier-Stiegen, H. Schneck, C. Blassl, R. Pedro Neves, W. Janni, T. Fehm, H. Neubauer Universitäts-Frauenklinik Düsseldorf, Forschungslabor Life Science Center, Düsseldorf, Heinrich-Heine Universität Düsseldorf, Düsseldorf, Universitäts-Frauenklinik Ulm, Ulm, The frequently altered phosphatidylinositol--kinase (PIK)/Akt signaling pathway is involved in the regulation of cellular processes required for breast carcinogenesis. The aim of the project was to develop a method to identify hotspot mutations in the PIKCA gene in circulating tumor cells (CTCs) of metastatic breast cancer (metbc) patients. From enrolled CTC-positive metbc patients a total number of 7 peripheral blood samples were analysed by CellSearch. Genomic DNA of enriched CTCs was isolated, amplified and analyzed for PIKCA mutations in exons 9 and 0 which lead to EK, EK or H07R amino acid changes and result in increased PIK activity. The mutations were detected by using SNaPshot-methodology comprising PCR amplification and single nucleotide primer extension. SNaPshot analysis was established using genomic DNA from different breast cancer cell lines and then successfully transferred to investigate blood samples and single cells. Overall, twelve hotspot mutations in either exon 9/EK (6/, 0%) or exon 0/H07R (6/, 0%) could be determined within 9 out of 7 (.8%) blood samples from 7 out of (.9%) patients; CTC counts ranged from to 978. PIKCA variants EK, EG and EA were not detected. Analysing the PIKCA genotype of CTCs has clinical relevance with respect to drug resistance, e.g. against HER-targeted therapy. The herein described approach including SNaPshot technology provides a simple method to characterize hotspot mutations within CTCs. Abstracts Oncol Res Treat 0;7(suppl ):

13 ID 9 CTCtrap Circulating Tumor Cells TheRapeutic APheresis: A novel biotechnology enabling personalized therapy for all cancer patients N. Kasprowicz, F. Farace, G. Attard, B. Rack, C. Vizler, R. Zamarchi 6, M. Scholz 7, A. Aaspõllu 8, A. Ventola 9, L. Terstappen 0, T. Fehm Heinrich Heine University of Duesseldorf, Department of Obstetrics and Gynaecology, Duesseldorf, Institut de Cancérologie Gustave Roussy, Villejuif, Frankreich Institute of Cancer Research, Großbritannien Ludwig-Maximilians University München, Munich, Biological Research Centre Hungarian Academy of Science (BRC), Ungarn 6 Oncology Institute of Veneto IRCCS, Italien 7 LEUKOCARE AG, Munich, 8 Asper Biotech Ltd, Estland 9 Aquamarijn Micro Filtration BV, The Netherlands 0 Twente University, Medical Cell Biophysics, Faculty of Science and Technology, The Netherlands Chemotherapy is slowly being supplemented by a new generation of drugs that recognize specific targets in or on cancer cells and has proven to be more effective with markedly fewer side effects. As a consequence renewed tumor analysis is required to redefine the optimal treatment regiment. However a biopsy can frequently not be obtained without risk and or discomfort to the patient. Circulating tumor cells (CTC) may circumvent this problem. CTC refer to cells that detach from a primary tumor or metastatic site, circulate in the peripheral blood and may form metastasis. CTC represent a liquid biopsy that can be used to tailor treatment for individual patients. CTC are however rare and can only be obtained for further characterization in a small fraction of patients. In the CTCtrap consortium universities, research institutions and SMEs are linked in a common effort, starting from the simple, but innovative view of using Therapeutic Apheresis (TA), as a way to collect CTC from peripheral blood in cancer patients. A new TA column will be developed to capture CTC and then reintroduce the blood devoid of tumor cells back into the body with the promise to obtain CTC in all patients at risk for recurrence or diagnosed with metastatic disease. The molecular characterization of these CTC is expected to gather new knowledge on metastasis mechanism, provide a risk assessment and the optimal therapy choice during the course of the disease of cancer patients. The new knowledge on CTC heterogeneity within cancer type and within individuals will allow for the tuning of CTCapheresis to specific cancer types. Prospective pilot studies will be setup to investigate the feasibility of the CTCapheresis in the clinic and their potential therapeutic benefit. Success of CTCapheresis will lead to a radical change in the diagnosis and treatment of solid tumors. ID 8 Plasma Pro-Enkephalin adds value to Proneurotensin for the risk prediction of incident breast cancer O. Melander, M. Orho-Melander, P. Almgren, J. Manjer, B. Hedblad, G. Engström, J. Struck, P. Nilsson, A. Bergmann, M. Belting Skåne University Hospital, Malm, Clinical Research Center, Malmö, Schweden Sphingotec GmbH, Hennigsdorf, Lund University, Section of Oncology, Malmö, Schweden Context: Neurotensin regulates breast cancer growth, and plasma Proneurotensin -7 (pro-nt), a stable peptide derived from the Neurotensin precursor, is associated with the development of breast cancer. Enkephalin may negatively regulate carcinogenesis and the growth of breast tumors and can be assessed in plasma by measuring a stable surrogate marker, Pro-Enkephalin A 9-9 (pro-enk). Objective: To test if plasma levels of pro-enk add value to pro-nt for the risk prediction of incident breast cancer. Design, Setting, and Participants: We measured pro-enk and pro-nt in fasting plasma from 99 women (mean age 8±.9 years) of the population based Malmö Diet and Cancer Study (MDCS) free from breast cancer prior to the baseline exam. We used Cox proportional hazards models to relate pro-enk and pro-nt to first breast cancer events (n = ) within years of follow-up. Results: Pro-ENK: Women belonging to quartiles, and of pro-enk compared to those of quartile had HRs for breast cancer of. (0.7.69),. (.7.) and.9 (.8.6). Pro-NT: As compared to women belonging to the st quartile of pro-nt, women belonging to quartiles, and of pro-nt had HRs for breast cancer of. (0.69.),.6 (0.9.8) and.7 (..0). Adding pro-enk to pro-nt provided added predictive value (p < 0.000), and HR for women with pro-enk in the st quartile and pro-nt in the th quartile (high risk group) were.7 (.8 7.0) as compared to women with pro-enk in quartiles and pro-nt in quartiles (low risk group). Women with one of the biomarkers in high risk still had a slightly increased risk (HR.7 (.6.)) as compared to the low risk group. Conclusion: Biomarker based risk prediction for the development of breast cancer is significantly improved, when plasma pro-enk is added to pro-nt. ID 60 Analysis of hypoxia-associated mirna in oral squamous cell carcinoma M. Kappler, J. Kotrba, U. Pabst, H. Wichmann, S. Rot, M. Bache, H. Taubert, A.W. Eckert Martin-Luther-Universität Halle-Wittenberg, Universitätsklinik und Poliklinik für Mund-, Kiefer- und Plastische Gesichtschirurgie, Halle (Saale), Martin-Luther-University Halle-Wittenberg, Department of Radiation Oncology, Halle (Saale), Friedrich Alexander University Erlangen, Department of Molecular Urology, Erlangen, Introduction: Tumor hypoxia plays a pivotal role in tumor progression. Hypoxic tumors are more insensible to radiation or chemotherapy. The identification of hypoxic tumors can improve the overall and disease free survival of oral squamous cell carcinoma [OSCC] patients. Micro RNA [mirna] are a class of small non-coding mrna s. Out of more than 600 mirna s only mirna 0 has been described as hypoxia-related in OSCC. The aim of the present investigation was to analyze tumor-specific and hypoxia-related mirna in OSCC and to compare with the expression level of Hypoxia-inducible factor α [HIF- α]. Materials and Methods: All expression profiles were performed at commercially available OSCC cell lines [XF, Cal, SAS and FaDu]. All cell lines were incubated under normoxic (% oxygen) and hypoxic conditions (% oxygen) over hours. The total amount of HIF-α protein was analyzed by real time protein managing system. Cell lines were investigated by deep sequencing and specific real-time PCR for each cell line in detail after cultivating under different oxygen pressures. Results: MiRNA 0 was upregulated in all cell lines under hypoxic conditions in comparision to normoxia. We found a -fold increase of mirna 0 (p < 0,00). Two other mirna (mirna 9, p = 0,0 and mirna, p = 0,07) were also hypoxia-associated in OSCC cell lines with marginal significance. Conclusion: To our knowledge, this is the first investigation detecting mirna 9 and mirna as hypoxia-related mirna in OSCC. We hypothesize, that OSCC tissues have a unique and specific mirna profile pattern. The detection of hypoxia-related mirna may help to stratify the therpeutical options in OSCC. 6 Oncol Res Treat 0;7(suppl ): Abstracts

14 ID 6 Circulating micrornas to monitor preoperative CRT in rectal cancer patients A. Azizian, J. Salendo, P. Jo, M. Grade, H. Wolff, M. Ghadimi, J. Gaedcke Universitätsmedizin Göttingen, Allgemein-, Viszeral- und Kinderchirurgie, Göttingen, Universitätsmedizin Göttingen, Strahlentherapie, Göttingen, Aim: Preoperative chemoradiotherapy (CRT) is the standard treatment for locally advanced rectal cancer. However tumorresponse is heterogenous. An early estimation of response during CRT is desirable as it could enable a modification of therapy at an early stage. To this day there is no reliable biomarker to monitor therapy response. MicroRNAs represent master regulators of gene expression and may therefore contribute to the diversity of response to CRT. The purpose of this investigation is the evaluation of micrornas as biomarkers for response monitoring during CRT in patients with locally advanced rectal cancer. Methods: In preliminary work five micrornas (mir-7, mir-8b, mir-0a, mir- and mir-9a_p) were identified as being differently expressed prior to preoperative CRT compared to healthy controls. MicroRNAs were analyzed in the plasma of patients (n = ) with locally advanced rectal cancer at four time points, namely: prior to-, during-, and after the CRT, and after the surgical resection. Isolation was carried out using Qiagen RNeasy mini kit columns after adding C. elegans mirna mimics as spike-ins. Expression levels between these time points were compared and correlated to clinical parameters. Results: mir- was excluded due to Ct values beyond 0. The remaining mirnas showed different expression levels over the time period. The reduction of the expression of mir-8b and mir-0a during CRT correlated significantly with a negative postoperative nodal state (p < 0,0). Conclusion: Circulating micrornas illustrate the potential to monitor the response to CRT in patients with locally advanced rectal cancer. The development of their expression could predict the nodal state of patients even before surgery. Further genome-wide analyses in a larger patient cohort is necessary. ID 7 DNA Methylation Biomarkers SHOX and SEPT9 in Blood for Monitoring Disease Progression in Cancer Patients D. Dietrich, A. Schröck, A. Leisse, F. Bootz, G. Kristiansen Institut für Pathologie, Uniklinikum Bonn, Bonn, Klinik und Poliklinik für Hals-, Nasen-, und Ohrenkrankheiten, Uniklinikum Bonn, Bonn, Diagnostic tests for monitoring the course of malignant diseases are of tremendous value for personalized treatment decisions. The identification of patients who are at increased risk for recurrence might allow subjecting them to an adjuvant treatment, i.e. radio- or chemotherapy. Free-circulating tumor DNA in blood holds great potential to detect postoperative residual tumor and occurrence of local and distant metastases. This study aimed to develop and validate a non-invasive biomarker test, to help monitoring the course of patients suffering from head and neck squamous cell carcinomas (HNSCC). Samples from HNSCC patients (cases) were obtained from patients who underwent clinical work-up for confirmed HNSCC at the University Hospital Bonn, Department of Otolaryngology, Head and Neck Surgery, University Hospital Bonn. 6 patients (controls) who underwent clinical work-up for suspected HNSCC without any evidence of presence of any malignancy. The HNSCC patients were followed up for up to one year. A sensitive and accurate qpcr assay was used to quantify methylation levels of the methylation biomarkers SHOX and SEPT9 in plasma. Increased copy numbers of free circulating methylated SHOX and SEPT9 were found in plasma from patients with HNSCC as compared to patients without malignant diseases. A significant decrease of biomarker level was found 0 days after tumor resection. Disease recurrence and survival was associated with an increase of SHOX and SEPT9 methylation in blood during follow-up. This assay may be used to monitor the disease progression in HNSCC patients and therefore identify patients which might benefit from adjuvant therapy. ID 7 Diagnostic and Prognostic Value of SHOX and SEPT9 DNA Methylation and Cytology in Benign, Paramalignant, and Malignant Pleural Effusions M. Jung, D. Dietrich, G. Kristiansen Institut für Pathologie, Uniklinikum Bonn, Bonn, Pleural effusions (PE) are a common clinical problem. The discrimination between benign (BPE), malignant (MPE) and paramalignant (PPE) pleural effusions is highly important to trigger the appropriate patients treatment. Cytology is the gold standard for diagnosing malignant pleural effusions. However, its sensitivity is limited due to the sometimes low abundance of tumor cells and the challenging assessment of cell morphology in cytological samples. This study aimed to develop and validate a diagnostic test, which allows for the highly specific detection of malignant cells in pleural effusions based on the DNA methylation biomarkers SHOX and SEPT9. A quantitative real-time PCR assay was developed which enabled the accurate and sensitive detection of SHOX and SEPT9 in PEs In a case control study comprising of patients (8 cases, 6 controls) PEs were analyzed by means of cytology and DNA methylation biomarkers. Cytological analysis as well as SHOX and SEPT9 methylation resulted in 00% specificity. The combined analysis of cytology and DNA methylation resulted in an increase of 7% positively classified PEs from cancer patients as compared to cytological analysis alone. Furthermore, DNA methylation analysis in PEs allowed predicting the overall survival in cancer patients (Kaplan-Meier analysis, p = 0.0 (SHOX), p = (SEPT9)). The developed test may be used as a diagnostic and prognostic adjunct to existing clinical and cytopathological investigations in patients with PEs of unclear etiology. ID 9 Assessment of breast volume changes during human pregnancy using a threedimensional surface assessment technique in the prospective CGATE study S.M. Jud, L. Haeberle, M.O. Schneider, J. von Wilucki, A. Hein, M.C. Koch, I. Linde, C.M. Bayer, F. Faschingbauer, E. Raabe, U. Dammer, R. Schulz-Wendtland, M.W. Beckmann, P.A. Fasching Universitäts-Frauenklinik Erlangen, Erlangen, Universität Erlangen, Radiologisches Institut Gynäkologische Radiologie, Erlangen, Objectives: Pregnancies and breastfeeding are two important protective factorsconcerning breast cancer risk, especially in younger age.molecular effect are rarely known.the aim of the present study was todocument changes in breast volume during pregnancy prospectively. Methods: In the prospective Clinical Gravidity Association Trial and Evaluation (CGATE) programme, pregnant women were followed up prospectively from gestational week to birth. Three-dimensional breast surface imaging andsubsequent volume assessments were performed. Factors influencing breast volumeat the end of the pregnancy were assessed using linear regression models. Results: 06 women were prospectivley followed from early pregnancy to birth. Breast volumes averaged 0 ml at the start of pregnancy and 6 ml at the end of pregnancy. The first, second and third quartiles of the volume increase were, 9, and ml, respectively. Breast size increased on average by 96 ml, regardless of the initial breast volume. Conclusions: Breast volume measurementduring pregnancyusing D-technique is feasible. Breast volume increases during pregnancy, but not all womens breastsrespond to pregnancy in the same way. Breast Abstracts Oncol Res Treat 0;7(suppl ): 7

15 volume changes during pregnancy arean interesting phenotype that can be easily assessed in further studies to examinebreast cancer risk. ID 07 Ki-67 is a prognostic factor in breast cancer patients findings of a large population-based cohort of a cancer registry E.C. Inwald, M. Klinkhammer-Schalke, F. Hofstädter, F. Zeman, M. Koller, M. Gerstenhauer, O. Ortmann Lehrstuhl für Frauenheilkunde und Geburtshilfe der Universität Regensburg am Caritas-Krankenhaus St. Josef, Regensburg, Tumorzentrum Regensburg, An-Institut der Universität Regensburg, Regensburg, Institut für Pathologie, Universität Regensburg, Regensburg, Zentrum für Klinische Studien, Universität Regensburg, Regensburg, Introduction: Beside the conventional established histopathological parameters the assessment of proliferation is an emerging field regarding treatment decisions in breast cancer patients. In this respect, the proliferation marker Ki-67 is intensely discussed. The intention of this population-based study was to evaluate routine use and value of Ki-67 as a prognostic parameter, and to analyze associations between Ki-67 and common histopathological and outcome parameters in routine clinical setting. Methods: This study included data from the clinical cancer registry Regensburg (Bavaria, Germany). Patients with primary, non-metastatic (M0), not neo-adjuvant treated breast cancer were considered. Within the total data pool of,69 patients who had been diagnosed between 00 and 0, in,68 (78%) cases Ki-67 was routinely determined. Results: Ki-67 expression was associated with all common histopathological factors (P < 0.00). Regarding survival analyses, Ki-67 was classified into five categories (reference category Ki-67 %) due to a non-linear relationship to overall survival (OS). In multivariable analyses, Ki-67 was identified as an independent prognostic parameter both for disease-free survival (DFS) (Ki-67>%, P = 0.00) and OS (Ki-67: 6 %, P = 0.07; Ki-67: 6 %, P = 0.0; Ki-67>%, P = 0.00) in breast cancer patients. The -year DFS (OS) rate was 86.7% (89.%) in patients with Ki-67 % in comparison with 7.8% (8.8%) in patients with a Ki-67 value >%. Conclusion: The current study was able to demonstrate that Ki-67 is already widely applied in routine clinical work. Ki-67 is associated with conventional histopathological parameters and, even more important, is an independent prognostic parameter for DFS and OS in breast cancer patients. ID 7 Detection and clinical relevance of hematogenous tumor cell dissemination in patients with ductal carcinoma in situ N. Krawczyk, M. Banys, I. Gruber, A. Hartkopf, D. Wallwiener, A. Staebler, S. Becker, T. Fehm, Universität, Frauenklinik, Düsseldorf, Marienkrankenhaus, Frauenklinik, Hamburg, Universität, Frauenklinik, Tübingen, Universität, Pathologie, Tübingen, Universität, Frauenklinik, Frankfurt, Background: Hematogenous tumor cell dissemination is considered a crucial step in systemic disease progression and predicts reduced clinical outcome in breast cancer patients. Only invasive cancers are assumed to shed tumor cells into the bloodstream and infiltrate lymph nodes. However, recent studies have revealed that disseminated tumor cells (DTCs) may be detected in the bone marrow of patients with preinvasive lesions, i.e. in ductal carcinoma in situ (DCIS). The purpose of this analysis was to examine the incidence and clinical value of DTC detection in DCIS patients. Methods: 0 patients treated for DCIS at the University Hospital Tuebingen, Germany between 00 and 0 were included into this analysis. Bone marrow (BM) aspirates were analyzed by immunocytochemistry (pancytokeratin antibody A-B/B) according to the ISHAGE evaluation criteria. Sentinel nodes were analyzed in 6 of these patients by extensive step sectioning and hematoxylin-eosin staining. Results: In 6 of 0 patients (6%) DTCs could be detected. No correlation was observed between BM status and tumor size, grading, histology or Van Nuys prognostic index. In two cases metastatic spread into lymph nodes was observed; isolated tumor cells in a sentinel node were found in one patient. A median follow up of months (range: months) was obtained for 6 patients. The differences in overall survival (OS) and disease-free survival (DFS) calculated by log-rank test were not statistically significant (OS: p = 0.088, DFS: p = 0.98). Conclusions: Tumor cell dissemination may be detected in patients diagnosed with DCIS. Whether these cells disseminate from real preinvasive mammary lesions or represent the earliest step of microinvasion, remains unclear. A longer follow-up may be necessary to accurately assess clinical value of these cells in DCIS patients. ID 6 The importance of MACC in colon cancer stem cells and adult stem cell signaling M. Hardt,, C. Lemos, D. Schumacher, C. Regenbrecht, E. Heiden, U. Stein, Max-Delbrück-Centrum für Molekulare Medizin, AG Prof. Dr. Ulrike Stein, Berlin, Charite Universitätsmedizin Berlin, Experimental and Clinical Research Center, Berlin, Charite Universitätsmedizin Berlin, Institut für Pathologie, Berlin, Charite Comprehensive Cancer Center, Berlin, The gene MACC (Metastasis-Associated in Colon Cancer ) has been affirmed as a biomarker for metastasis in colorectal cancer (CRC). Only a subset of cells within a tumor is endowed with the potential to propagate the latter and concomitantly drives metastasis. Following this cancer stem cell hypothesis, MACC s role at the level of the stem cell is of crucial importance and investigated herein. We seek to analyze the expression of MACC directly in the stem cell population of CRC patient material, cell lines as well as mouse models available in our lab. For this purpose, primary cultures of patient-derived organoids are currently being expanded to allow for efficient fluorescent-activated cell sorting. Likewise, the intestinal stem cell populations of wild type and mouse models with engineered MACC expression will be assessed. At the cell line level, we could already show that the sorting of SW60 cells via CD enables differential enrichment of the intestinal stem cell marker Lgr together with MACC. In parallel, we aim to elucidate MACC s role in stem cell signaling. Of note, we found that MACC levels modulate the expression of Oct in CRC cell lines. Overexpression of MACC in CaCo and SW80 cells was related to an increase in Oct mrna and protein expression. Consistently, knockdown of MACC in CaCo and SW60 cells resulted in decreased levels of Oct. In conclusion, we provide here the first molecular link between MACC and stem cells. Additional studies will help clarify the nature of the MACC and Oct interaction and its functional relevance. The finding that the expression of MACC is indeed focused in cancer stem cells might further increase its prognostic value and accentuate the importance of MACC in carcinogenesis. 8 Oncol Res Treat 0;7(suppl ): Abstracts

16 ID Detection of somatic mutations by next-generation sequencing in a clinical setting C. Schroeder,, M. Sturm, S. Junker, M. Bitzer, N. Malek, B. Sipos, H.-G. Rammensee, O. Rieß,, P. Bauer, Institute of Medical Genetics and Applied Genomics, Tübingen, Genes and Therapy, Tübingen, University Hospital Tübingen, Department of Internal Medicine I, Tübingen, University Hospital Tübingen, Department of Pathology, Tübingen, Institute for Cell Biology, Department of Immunology, Tübingen, Next-generation-sequencing (NGS) is a key technology for high-throughput identification of genomic biomarkers that are of prognostic or therapeutic relevance. An increasing number of biomarkers, either of prognostic or therapeutic relevance, are reported by case reports and clinical trials. To face these developments, we founded an interdisciplinary clinical-oncogenetic tumor board at our hospital to coordinate sequencing efforts and discuss sequencing results. Specialists involved in this process are pathologists, geneticists and oncologists. Currently, we offer two cancer gene panels (8 genes hotspot panel, 8 genes complete coding sequence) and exome/transcriptome sequencing to selected patients. Up to now, we analyzed tumor samples with our hotspot panel and a total of samples with our 8 cancer gene panel. The analysis included both FFPE material and native tumor tissue from different cancer entities. Our analysis workflow is automated and variants are tracked by our inhouse database. We were able to identify mutations in common cancer genes like KRAS, TP, CTNNB, PIKCA and ERBB. Each variant was validated to be somatic (comparison to reference sample, e.g. blood) and confirmed by a second independent sequencing method (e.g. Sanger sequencing). Medical reports were generated within four weeks summarizing variants and current literature. Our data suggest that detection of somatic mutations can be highly automated and standardized. Though, clinical interpretation of the majority of somatic mutations remains challenging and functional studies are needed for translation of somatic mutations into therapeutic decisions. ID Changes in the level of plasma micrornas in rectal cancer patients J. Salendo Universitätsmedizin Göttingen, Klinik für Allgemein Chirurgie, Göttingen, Background: The identification of response in locally advanced rectal cancer (RC) to a -FU based chemoradiotherapy (CRT) is a crucial step towards an individualization of the therapy. Recently, the impact of micrornas (mirnas) on progression or resistance in cancer has been described. Although their expression changes in patients blood has recently been described in different cancer types data in rectal cancer are scarce. Materials/Methods: mirnas were extracted from patient and healthy control plasma. The 0 differentially regulated mirnas were retrieved from the comparison of rectal cancer and normal tissue based on mirna microarray analyses. They were analysed in a first plasma set materials of RC patients and gender matched- healthy controls. Furthermore, a subset of mirnas was further analysed in plasma of 78 individuals, inclusive the expressions before and after the treatment. Results: Eight mirnas were chosen for further analyses. Subsequently, in the analysis using larger cohort three mirnas could be further confirmed. Interestingly, all mirnas that were overexpressed in tumor tend to have lower expressions in the plasma of RC patients than healthy patients. Comparing pre- and post-therapeutical expressions of patients that underwent neoadjuvant CRT all mirnas were significantly differentially expressed. Conclusion: Our study demonstrated changes on the level of circulating mirna between RC and healthy patients. Furthermore we identified mirnas responsive to the neoadjuvant CRT, highlighting the potential of plasma mirna to observe the response in RC patients. The impact of the level changes after treatment on prognosis will be shown in a comprehensive approach. ID Run-in phase of prospective WSG ADAPT HR+/HER- trial demonstrates feasibility of early endocrine sensitivity prediction by Recurrence Score and conventional parameters in clinical routine. N. Harbeck, O. Gluz,, D. Hofmann, H.H. Kreipe, M. Christgen, C. Svedman, S. Shak, S. Kümmel 6, B. Nuding 7, N. Rezai 8, H. Forstbauer 9, R. Würstlein,0, R.E. Kates, U. Nitz, Universitätsfrauenklinik Großhadern, Brustzentrum der LMU München, München, Westdeutsche Studiengruppe GmbH, Mönchengladbach, Ev. Bethesda Krankenhaus, Brustzentrum Niederrhein, Mönchengladbach, Medizinische Hochschule Hannover, Institut für Pathologie, Hannover, Genomic Health, Inc., Redwood City, 6 Kliniken Essen-Mitte, Klinik für Senologie/Brustzentrum, Essen, 7 Ev. Krankenhaus Bergisch Gladbach, Brustzentrum, Bergisch Gladbach, 8 Luisenkrankenhaus Düsseldorf, Brustzentrum, Düsseldorf, 9 Praxisnetzwerk Troisdorf, Hämatologie/Intern. Onkologie, Troisdorf, 0 Universitätsfrauenklinik Großhadern, Brustzentrum der LMU München, München, Background: Endocrine sensitivity by proliferation response to shortterm preoperative endocrine therapy (ET) is currently not included in adjuvant chemotherapy (CTx) decisions in early breast cancer (ebc). Methods: The ADAPT HR+/HER- trial includes N0- ebc patients (pts) being candidates for adjuvant CTx; it aims to spare CTx by combining genomic assessment by Oncotype DX and endocrine sensitivity testing. Pts receive -week preoperative ET: aromatase inhibitors (AI) or tamoxifen. Pts with low (0 ) Recurrence Score (RS) or intermediate RS ( ) and ET response (central Ki-67 post <0%) are recommended to forego adjuvant CTx («low-risk»). Results: By 9/0, 6 pts (median age y) from study sites were enrolled. At st pre-planned analysis (/0; n = 6): RS low.6%, RS intermediate 7.7%, RS high 0.7%; respective risk group responders (Ki 67 post <0%): 8.%, 7.9%, 0.0% (p < 0.00 comparing low/intermediate vs. high). Median Ki 67 level drop (percentage of pre-treatment value) was % in pre- (n = 0) vs. 7% in postmenopausal pts (n = ) (p < 0.00); median drop by RS group was similar: low 6%, intermediate %, high 6% (p = 0.8). Ki-67 pre, endocrine regimen/menopausal status, and RS were independent predictors for Ki 67 post. Conclusions: The ADAPT Run-In Phase confirms design estimates of RS and proliferation response to induction ET with >70% ET responders with intermediate genomic risk who could potentially be spared CTx. It indicates feasibility of combining static and dynamic biomarker assessment for individualized therapy in ebc. Survival non-inferiority of intermediate RS/responders vs. low RS pts (active control) will be tested in the ADAPT main phase. Abstracts Oncol Res Treat 0;7(suppl ): 9

17 Breast Cancer Adjuvant Therapy ID 078 Endoxifen and fulvestrant regulate gene expression of estrogen receptor alpha and its co-activators DEADbox and 7 M. Hirschfeld, V. Neumann, M. Jäger, T. Erbes, E. Stickeler Universitätsfrauenklinik Freiburg, Molekulare Onkologie, Freiburg, Background: Application of anti-estrogens remains a standard therapy in ERα -positive breast cancer. Endoxifen acts as a selective receptor down-modulator of ERα function, while fulvestrant acts as a selective receptor down-regulator via an increased ERα inhibition and degradation. RNA helicases p68 (DDX) and p7 (DDX7) act as co-activators of ERα. DDX7 expression correlates with decreased Her/neu levels, extended relapse-free periods, and an increase in overall survival rates. In contrast, DDX expression is associated with increased Her/neu levels and higher tumor grading, but not correlated with relapse-free or overall survival. This study aimed for the investigation of potential regulatory effects of the anti-estrogens on the expression of ERα, DDX and 7. Methods: In vitro application of endoxifen and fulvestrant. Results: Both drugs created a significant decrease of mrna and protein expression levels of all target genes. DDX and 7 expression levels generally decreased, whereat endoxifen treatment triggered a stronger effect than fulvestrant. While both ERα antagonists caused a uniform decrease in ERα protein levels, DDX protein levels were differentially affected. Fulvestrant triggered a uniform downregulation of DDX and 7. In contrast, endoxifen stimulation resulted in an up-regulation of DDX and 7 protein. Conclusion: Both ERα antagonists show regulatory effects on ERα, DDX and 7 expression. The in vitro data might explain individual therapeutic efficacy or the occurrence of resistance against endocrine therapy dependent on cellular context. The elucidation of DDX status might serve as a useful prognostic tool to estimate efficacy of anti-estrogen treatment in breast cancer therapy. ID 0 Chemotherapy in breast cancer patients predictors of non-adherence to guidelines L. Schwentner, A. Wöckel, R. Van Ewijk, W. Janni, R. Kreienberg, M. Blettner, S. Singer, Universität Ulm, Frauenheilkunde und Geburtshilfe, Ulm, Universität Mainz, IMBEI, Mainz, Background: Guideline (GL) adherence in breast cancer is a significant survival predictor. We investigate what patient-related and physician-related factors predict guideline non-adherence. Methods: 6 primary breast cancer patients were followed from hospital admission till systemic treatment beginning. Multi-disciplinary tumorboard chemotherapy (CT) decisions were documented. Patients completed the Patient Health Questionnaire for psychiatric comorbidities, EORTC Quality of Life (QoL) core questionnaire and questions on specific fears of receiving CT. Somatic comorbidity was assessed by ASA score. Potential predictors of a) treatment decision and b) GL non-adherence were tested in multivariate logistic regressions. Results: GL indicated no CT in 8.% of cases. Tumorboards suggested CT-administration in 9.8%. Reasons for GL deviations were rarely given. 8.% of patients agreed with CT-decisions. Reasons for patient non-agreement were fear and cost-benefit unbalance. Actual patient treatment was GL-conform in 98.%: there were cases of under- and 0 of over-treatment. 0.% of patients had somatic and.6% psychiatric comorbidity. 6% reported being very afraid of CT. Tumorboards less often prescribed CT to patients >7 years (OR 0.), with somatic comorbidities (OR 0.) or high fear (0.6). Actual treatment more often deviated from GL for >7 years (OR 0.) and poor QoL (OR 0.7). Neither tumorboard decisions nor actual treatment correlated with education or psychiatric comorbidity. Conclusions: Age, somatic comorbidity, fears regarding CT and QoL are related to CT-decisions. ID Vaginal estriol-lactobacilli combination (Gynoflor ) therapy and sexual quality of life in breast cancer patients on aromatase inhibitors with atrophic vaginitis M. Mögele, S. Buchholz, A. Lintermans, G. Bellen, V. Prasauskas, O. Ortmann, P. Grob, P. Neven, G. Donders Lehrstuhl für Frauenheilkunde und Geburtshilfe der Universität Regensburg am Caritas Krankenhaus St. Josef, Regensburg, University Hospital Gasthuisberg Leuven, Belgium, Leuven, Belgium, Belgien Femicare vzw, Clinical Research for Women, Tienen, Belgium, Belgien Medinova AG, Zurich, Switzerland, Zurich, University Antwerp, Belgium, Antwerp, Belgien Besides the pharmacology parameters this clinical study investigated also effect on sexual domain of QOL during the treatment of BC survivors on AI with vaginal ultra-low-dose estriol-lactobacilli combination tablets Gynoflor. This was an open label bicentric clinical study in 6 postmenopausal BC survivors on AIs suffering from vaginal atrophy induced sexual disorders. Clinical vaginal atrophy symptoms were assessed by scoring with an -point estimation scale (0 = not at all, 0 = worst imaginable feeling). Sexuality parameters of QOL and medication compliance were recorded in patient s diary. Recruited women underwent an initial treatment for weeks ( vaginal tablet daily) followed by maintenance therapy ( vaginal tablets weekly) for 8 weeks. Vaginal dryness continuously improved from a median of score 8 at entry to score at the end of initial therapy, and median score at the end of maintenance therapy. Previous normal sexual activity before the BC diagnosis reported (88%) women. During the BC treatment with AIs this number was dramatically decreased, at study entry only (9%) of women were sexually active, whereas at the end of the study already 7 (%) women reported sexual intercourse. The FSSEI demonstrated clear trend for improvement of main domains of sexual QOL (desire, arousal, orgasm and satisfaction), whereas the statistically significant result due to a small number of subjects were seen only for few parameters. Local vaginal ultra-low-dose estriol-lactobacilli therapy (Gynoflor ) in postmenopausal breast cancer (BC) survivors on aromatase inhibitors (AIs) with atrophic vaginitis is a safe treatment (presented earlier) with a positive impact on the sexual domain of quality of life (QOL). ID Guideline Adherence in the Therapy of Young Mothers with Breast Cancer in Germany D. Fischer, M. Hedderich, A. Heinrich, K. Baumann, A. Rody, A. Waldmann Uni Lübeck, Frauenklinik, Lübeck, UKE, Hamburg, Uni Lübeck, Institut für Sozialmedizin und Epidemiologie (ISE), Lübeck, Background and Objective: The aim of the study is to analyse the guideline adherence in the treatment of young breast cancer patients in an adjuvant setting. Materials and Methods: A retrospective study analyzed the treatment of 0 young mothers first diagnosed between 00 and 0 with primary breast cancer according to the AGO guideline adherence. The patients participated in a resident mother-child program and were compared to age-heterogeneous cohorts. Results: The median age of the young cohort was 9 years. Their tumors were significantly higher in stage and grading than the older group (% 0 Oncol Res Treat 0;7(suppl ): Abstracts

18 vs. % >T stage, 7% vs. 6% N+, % vs. 9% G). The biology of the tumors was significantly worse. Therefore young patients got a significantly more aggressive therapy than older women. The percentage of guideline adherence for the therapeutic modalities for BCT, mastectomy, axillary dissection, hormone therapy, chemotherapy and antibody therapy was >9% in the young patients. However, chemotherapy results differ significantly in comparison to the older group. Conclusion: Young breast cancer patients participating in a resident mother-child program are diagnosed in a worse stage and their carcinomas are more aggressive. Their treatment shows a high level of AGO guideline adherence. It remains unclear to what extent the guideline adherence improves overall survival and disease free survival in this group. ID 76 Long-term results of trastuzumab in the adjuvant treatment of breast cancer, with focus on elderly patients P. Dall, G. Lenzen, T. Göhler, G. Feisel-Schwickeradi, T. Koch, V. Heilmann 6, C. Schindler 7, J. Wilke 8, H. Tesch 9, J. Selbach 0, J. Eggert, A. Hinke Städt. Klinikum, Frauenklinik, Lüneburg, Practice, Osnabrück, Practice, Dresden, Klinikum Kassel, Kassel, Klinikum Nürnberg Nord, Frauenklinik, Nürnberg, 6 Practice, Günzburg, 7 Practice, Leipzig, 8 Practice, Fürth, 9 Onkologie Bethanien, Frankfurt, 0 Practice, Duisburg, Practice, Moers, WiSP, Langenfeld, Trastuzumab (T) is a standard treatment in patients (pts) with HER+ early breast cancer in addition to (neo)adjuvant chemotherapy (CT). This German prospective observation study examined the generalizability of the results from pivotal randomized studies, with the focus on benefits and risks for elderly patients (EP) in the present analysis. 07 pts were enrolled from 006 to 0, unselected regarding age or concomitant/sequential adjuvant CT. Among 90 evaluable pts, 0 were EP 6 years (y) of age (6%). This contrasts to the pivotal studies, with only 6% beyond 6 y in the NSABP/NCCTG studies. More than half of the pts had pt, with EP more often presenting with a larger tumor (6 vs. 8%, p <.000). As expected, performance status was more impaired in EP (ECOG 0: vs 6%, p <.000). 9% received CT, 78% as adjuvant, % as neoadjuvant treatment (in EP only 8%). The proportion without any (neo)adjuvant CT was higher in EP (8 vs. %). T was stopped prematurely more often in EP ( vs 8%, p =.0). After up to a maximum follow-up of 8 y, 70 relapses were reported so far. Recurrence-free survival is 9.7, 89.8 and 8.9% after, and y, respectively, in EP only slightly lower with 9.9, 89. and 8.6%, not statistically significant (p =.8, HR =.7, 9% CI 0.9.7). In the EP subgroup the incidence of cardiac events of all grades was only slightly increased (.6 vs..9% overall). The maturing follow-up data confirm the beneficial results from the randomized studies. Moreover, the data show that a similar anti-tumor efficiency can be achieved in EP, and suggest that minor age-related differences detected with respect to adjuvant treatment duration, aggressiveness and toxicity do not impair the long-term outcome. ID 9 Suitable patients for IORT at the Interdisciplinary Breast Cancer Center Mannheim D. Astor, E. Sperk, A. Keller, G. Welzel, A. Gerhardt, M. Sütterlin, F. Wenz Medical Center Mannheim, University of Heidelberg, Department of Radiation Oncology, Mannheim, Medical Center Mannheim, University of Heidelberg, Department of Obstetrics and Gynecology, Mannheim, Background: Recommendations for suitable patients for intraoperative radiotherapy (IORT) alone are available from the ESTRO (European Society for Radiotherapy and Oncology) and ASTRO (American Society for Radiation Oncology). Several TARGIT (TARGeted Intraoperative radiotherapy) trials under guidance of the Interdisciplinary Breast Cancer Center Mannheim (TARGIT E elderly, TARGIT C consolidation, TARGIT BQR boost quality registry ) also include patients with other characteristics. Methods: Between 0/0 and /09, 0 cases were treated. Complete data sets for age, stage (T, N, M), histology, hormone receptor status and metastasis were available in 08 cases. Recommendations are as follows: ESTRO: >0 years, invasive ductal carcinoma/other favourable histology (IDC), T- ( cm), N0, any hormone receptor status, M0; ASTRO: 60 years, IDC, T- ( cm), N0, M0; TARGIT E: 70 years, IDC, T, N0, any hormone receptor status, M0; TARGIT C: 0 years, IDC, T- ( cm), N0, positive hormone receptor status, M0; TARGIT BQR: every age, every histology, T- (.cm), any hormone receptor status, N0/+, M0/+. Results: Out of the 08 available cases, 79 cases (.%) are suitable for IORT regarding the ESTRO and 7 (.8%) regarding the ASTRO recommendations. 8 (7.%) patients were suitable for the TARGIT E trial, 8 (.%) for TARGIT C and 67 (60.6%) for TARGIT BQR. Conclusion: The TARGIT E and C inclusion criteria for IORT alone are more conservative than the ESTRO recommendations. Nearly two thirds of the treated patients could be allocated to an IORT boost. ID 6 The prognostic relevance of disseminated tumor cells in primary breast cancer patients results from a large single-center study A. Hartkopf, T. Fehm, M. Wallwiener, M. Hahn, D. Wallwiener, S. Becker, E. Solomayer, F.-A. Taran Universität Tübingen, Tübingen, Background: The presence of disseminated tumor cells (DTC) in the bone marrow (BM) of primary breast cancer (PBC) patients is associated with a worsened prognosis. This is the largest single-center study that determines the impact of DTC on disease free (DFS) and overall survival. Methods: BM aspirates were collected from patients that underwent surgery for PBC at Tuebingen University Hospital, Germany, between 0/00 and 0/0. DTC were identified by immunocytochemistry (pancytokeratin antibody A/B) and cytomorphology. The DTC-status was compared to other prognostic factors by use of the chi-squared test and survival was analyzed in an univariate (log-rank test) and multivariate analysis (cox regression). Results:, patients were available for this retrospective analysis. Of these 80 (6%) were DTC-positive. DTC-positivity was associated with larger tumors (p < 0.00), positive lymph nodes (p = 0.00), ER-negative (p = 0.0) and PR-negative (p < 0.00) patients. DTC-positive patients were at an increased risk of death (median OS of DTC- vs. DTC+ patients: n. r. (not reached) vs. (9% CI: 8) months, p = 0.00) and disease relapse (median DFS was n. r. in either groups, p < 0.00). Independent factors for OS / DFS were DTC-status, menopausal-status, tumor size, nodal-status, ER-status and PR-status / DTC-status, tumor size, nodal-status and ER-status. Abstracts Oncol Res Treat 0;7(suppl ):

19 Conclusion: This study confirms the strong and independent prognostic value of DTC-determination in primary breast cancer patients. The DTC-status might help to identify patients that are at an increased risk of death or disease relapse and thus in need for an aggressive adjuvant treatment. ID 70 Application of integrative medicine by postmenopausal breast cancer patients in the PreFace Phase IV study a prospective, longitudinal trial C.C. Hack, M.W. Beckmann, A. Hein, C.M. Bayer, C. Rauh, K. Almstedt, N.B.M. Hüttner, W. Janni, T. Fehm, N. Maass, A. Rody, N. Fersis 6, D. Wallwiener 7, J. Hübner 8, P.A. Fasching,9 Frauenklinik University Hospital Erlangen, Department of Gynecology and Obstetrics, Erlangen, University Hospital Ulm, Department of Gynecology and Obstetrics, Ulm, University Hospital Düsseldorf, Department of Gynecology and Obstetrics, Düsseldorf, University Hospital Aachen, Department of Gynecology and Obstetrics, Aachen, University Hospital Schleswig-Holstein, Campus Lübeck, Department of Gynecology and Obstetrics, Lübeck, 6 Hospital Chemnitz, Department of Gynecology and Obstetrics, Chemnitz, 7 University Hospital Tübingen, Department of Gynecology and Obstetrics, Tübingen, 8 German Cancer Society, Berlin, 9 University of California at Los Angeles, David Geffen School of Medicine, Department of Medicine, Division of Hematology/Oncology, Los Angeles, CA, USA Aim: It is known, that a relevant number of breast cancer patients applies integrative medicine in addition to conventional cancer therapy. In particular modern cancer therapies as aromatase inhibitors are associated with considerable adverse effects like ostealgia and arthralgia, what could trigger above all the application of integrative medicine to alleviate the pain. Aim of this presented trial is the registration of the usage of integrative medicine in the adjuvant therapy status during the course of treatment. Methods: The PreFace Study is a Phase IV Study, where postmenopausal and hormone-receptor-positive breast cancer patients are medicated with the aromatase inhibitor Letrozol. As part of a patient diary all patients have been asked to document which integrative medicine has been applied at the time before Letrozol therapy (month 0), at month 6 and at month after start of therapy. For this purpose the PRIO questionnaire was used. Results: 9 patients of in all gave particulars to the application of integrative medicine within the total study. Respectively 0%, % and % of the patients have stated to use actively integrative medicine at month 0, 6 and. Before start of therapy the motivation at % of the users was the promotion of cancer healing and at 6% the improvement of quality of life. During the course of the PreFace study this motivation dwindled significantly. The most frequently documented methods at start of therapy was nutritional supplement (%), intake of vitamins (%) and the devotions (9%). Mistletoe therapy was only mentioned from % of the patients. The frequency of usage of the most integrative methods did not change during the observation period. Conclusion: Integrative medicine is still frequently used by breast cancer patients. Some methods such as the mistletoe therapy are conducted today only in rare cases from postmenopausal breast cancer patients. ID 80 Radiation-induced modulation in the distribution of lymphocytes in breast cancer patients E.K. Sage, M. Sedelmayr, M. Gehrmann, C. Bayer, D. Schilling, M.N. Duma, T.E. Schmid, H. Geinitz, G. Multhoff Klinikum rechts der Isar der TU München, Klinik und Poliklinik für Strahlentherapie und Radiologische Onkologie, München, Krankenhaus der Barmherzigen Schwestern, Radio-Onkologie, Linz, Background: Mounting evidence indicates that radiotherapy has a modulating impact on the immune system. We examined immune cells in peripheral blood of breast cancer patients with or without chemotherapy (ChT) before radiotherapy (RT) with respect to percentual distribution. Methods: Blood samples of 0 patients with breast cancer were collected before, at 0 Gy and at the end of RT, as well as six weeks and six months after RT. Eight of these patients received adjuvant chemotherapy before RT. Five healthy volunteers were used as control. Lymphocyte subpopulations were analysed by flow-cytometry. Results: Our results show that ChT affects the lymphocytes count more than RT. Particularly B cells are impacted by ChT. Compared to the control (.8 ±.%) the number of B cells is reduced significantly to 0.8 ± 0.% by ChT. There was a partial recovery during RT. Regarding patients with RT only, a significant decrease in B cell count from.8 ± 0.8% before RT to 8.0 ± 0.7% at the end of RT was observed. Six months after RT the percentage of B cells almost reaches control level (.0 ± 0.6%). The fraction of Natural killer cells was elevated after ChT (.8 ±.7%) and decreased to normal levels (9. ±.%) at the end of RT. During RT there was a transient increase in the amount of regulatory T cells of ± % of the initial level, which was more pronounced without previous ChT ( ± %). Conclusion: Our results indicate that B and T cells are differently sensible to RT and ChT. There are also differences in the recovery time of immune cells after chemo- and radiotherapy. A clearer understanding of the impact of radiation and chemotherapeutic agents on immune cells and activation markers could lead towards new innovative therapy concepts combining RT and ChT with immunotherapy. ID 0 Effects of estriol on growth, gene expression and estrogen response element activation in human breast cancer cell lines C. Lattrich, M. Diller, S. Schüler, S. Buchholz, O. Treeck, O. Ortmann Lehrstuhl für Frauenheilkunde und Geburtshilfe der Universität Regensburg am Caritas-Krankenhaus St. Josef, Regensburg, Introduction: Local application of estradiol (E) to treat vulvovaginal atrophy in postmenopausal breast cancer patients receiving aromatase inhibitors is known to elevate serum estradiol levels and thereby might counteract breast cancer therapy. Thus, vaginal application of estriol (E) has been recommended for these patients. However, it is unclear to what extent E stimulates breast cancer cell growth. In this study, we examined the effect of E on growth and gene expression of two human breast cancer cell lines. Methods: We used an established in vitro cell culture assay and compared the effect of E and E on growth of the estrogen receptor alpha-positive breast cancer cell lines MCF-7 and T-7D testing a wide range of hormone concentrations of 0 - to 0-7 M. E effects on gene expression were examined by means of reporter gene assays, RT-qPCR and Western blot analysis. Results: E acted as a potent estrogen and exerted a mitogenic effect on T-7D and MCF-7 cells at concentrations of 0-9 M (88 pg/ml) and higher. With regard to activation of an estrogen response element (ERE) in breast cancer cells, effects of E were visible at 0-0 M. The same concentrations of E activated expression of the estrogen-responsive gene PR and of the proliferation genes cyclin A, cyclin B, Ki-67, c-myc and b-myb, providing molecular mechanisms underlying the observed growth increase. Oncol Res Treat 0;7(suppl ): Abstracts

20 Conclusions: Like E, low levels of E were able to trigger an robust estrogenic response in breast cancer cells. Thus, E treatment for postmenopausal breast cancer patients with vulvovaginal atrophy has to be indicated with caution. ID SEPTEMBRA a pilot study to detect and analyze circulating tumor cells in breast cancer patients N.S. Kasprowicz, E. Honisch, S. Mohrmann, J. Fischer, D. Niederacher, N.H. Stoecklein, T.N. Fehm Universitätsklinikum, Frauenklinik, Düsseldorf, Universitätsklinikum, Institut für Transplantationsdiagnostik und Zelltherapeutika, Düsseldorf, Universitätsklinikum, Klinik für Allgemein-, Viszeral- und Kinderchirurgie, Düsseldorf, Background: Circulating tumor cells (CTC) are promising biomarkers for diagnosis and systemic therapy in breast, colon and prostate cancer. However, their low detection rates especially in non-metastatic patients limit currently their clinical use. Leukapheresis may provide a method to increase CTC yields by analyzing an increased blood volume. Methods: To evaluate leukapheresis in non-metastastic breast cancer (BC) patients, we initiated a prospective pilot-study, SEPTEMBRA. Before and after primary surgery of BC, the patients underwent diagnostic leukapheresis (DLA). Simultaneously, 7. ml of peripheral blood was drawn to be analyzed by the current gold-standard, the CellSearch-System (Veridex, USA). We compared DLA products with peripheral blood samples regarding prevalence and quantity of CTC. Statistical analysis was performed with exact Fisher-test and Mann-Withney-U-test. P-value of <0.0 was regarded as significant. Results: So far, we have included 6 patients with non-metastatic breast cancer. Analysis was performed on peripheral blood samples and DLA products. Analysis shows a significant higher prevalence of CTC in DLA products than in the peripheral blood samples (8% versus 9% p < 0.00). Furthermore, the number of CTCs was higher in DLA products (median, range 0 0 vs. median 0, range 0 ; p < 0,00). Conclusion: Our results suggest that leukapheresis (DLA) seems to be able to increase both CTC detection rate as well as CTC yields. Thus we believe that leukapheresis will help to exploit the full clinical potential of CTC as biomarkers for diagnosis and systemic therapy. In the future, we plan to extend this study to metastatic patients and those with neoadjuvant treatment. ID 90 Bilateral breast cancer: Risk factors with impact on clinical outcome A. Meyer,, A. Köhler, R. Hermann,, H. Christiansen Gemeinschaftspraxis für Strahlentherapie, Hildesheim, Medizinische Hochschule Hannover, Klinik für Strahlentherapie, Hannover, Zentrum für Strahlentherapie und Radioonkologie, Westerstede, Introduction: Unilateral breast cancer patients have a fold increased risk of the development of contralateral breast cancer. Little is known about the prognostic outlook after treatment of second primary cancer. Patients and Methods: pat. with bilateral metachronous or synchronous breast cancer were treated with radiotherapy of the breast or the thoracic wall between 0/998 and /008. Median follow-up was 7 months. Synchronous bilateral breast cancer was defined as occurence of second contralateral tumour within 6 months of diagnosis of first tumor. Results: Further outcome after and years regarding overall survival was 8% and 66%, local recurrence-free survival 8% and 7% and metastasis-free survival 77% and 60%. Synchronous or metachronous occurence of contralaeteral breast cancer had no impact on further outcome regarding the above mentioned end points (p > 0,0). In patients with metachronous contralateral breast cancer the interval between the two breast cancer events had no impact on further outcome (p > 0,0). Statistically significant impact factors for the whole cohort were application of endocrine therapy on local recurrence-free survival (p = 0,06), age > 60 at time of occurence of contralateral breast cancer (p = 0,009) and stage (p < 0,00) on metastasis-free survival, and stage (p < 0,00) on overall survival. Conclusions: Patients with synchronous or metachronous bilateral breast cancer do not differ regarding further outcome. However, age at occurence of contralateral breast cancer has strong impact on metastasis-free survival. ID 00 Impact of adjuvant treatment decisions for survival outcomes in very elderly breast cancer patients ( 7 years) J. Bonacker, A. Stachs, S. Hartmann, J. Stubert, M. Dieterich, B. Gerber, T. Reimer Universität Rostock, Gynäkologie, Rostock, Background: The optimal management of adjuvant breast cancer in very elderly women is controversial. The lack of data from clinical trials reduces the value of published guidelines. The aim of our study was to evaluate the impact of prognostic factors and therapeutic applications on survival. Methods: This unicentric study included breast cancer patients aged 7 years who received adjuvant therapy between 000 and 009. Reported treatment modalities were categorized as optimal or suboptimal standard. Factors with impact on survival (disease-free [DFS], breast cancer-specific [BCSS], and overall survival [OS]) were identified by logrank test and Cox regression. Results: Among patients, 7 women (8.%) refused any surgery. The rates of suboptimal standard treatment were higher for endocrine (.8%), systemic (0.8%), and radiation therapy (8.8%). Using log-rank test standard radiotherapy, hormone receptor status, grading, tumor size, and nodal status were significantly related with DFS. The corresponding factors with an impact on BCSS were: standard endocrine therapy, hormone receptor, HER, and nodal status. Age was significantly associated with OS. Various treatment modalities and prognostic factors maintained their statistical impact on OS. The multivariate analysis will be presented at the DKK 0. Conclusions: Among this selected cohort, 6.7% of patients were treated with suboptimal standard. The general acceptance of published guidelines showed only a marginal effect on BCSS. However, standard radiation (DFS) and endocrine therapy (BCSS) revealed a significant impact on survival outcomes. Both should be considered in treatment decisions with respect to patient s health status. ID 7 Pathological complete response rates in patients with BRCA/-associated breast cancer after neoadjuvant chemotherapy L. Richters,, K. Rhiem, B. Wappenschmidt, M. Kiechle, R. Schmutzler Universitätsklinkum Köln, Zentrum für Familiären Brust- und Eierstockkrebs, Köln, Universitätsklinikum Köln, Klinik und Poliklinik für Gynäkologie und Geburtshilfe, Köln, Frauenklinik rechts der Isar, München, Purpose: As shown in previous studies, hereditary breast cancer responds differently to diverse chemotherapeutics. Therefore the present paper investigates retrospectively the rate of pathological complete response (pcr: ypt0 ypn0) and overall response (ORR) in Patients with BRCA/-associated breast cancer after differing neoadjuvant regimens. Methods: cases of BRCA/-associated breast cancer (BRCA: n = 0; BRCA: n = ) treated with neoadjuvant chemotherapy could be identified in our collective between 996 and 0. Mainly inva- Abstracts Oncol Res Treat 0;7(suppl ):

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