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CP Breast & Gynecological

Summary

Heidelberg is among the leading certified breast cancer centers in Germany. The Division of Gynecologic Oncology plays a key role in the German Breast Group. The program coordinates more than 70 phase I-IV trials with concomitant translational research programs. Significant achievements include the discovery and evaluation of prognostic markers and the development and implementation of new treatment strategies, including intensity-modulated radiotherapy. Additional achievements are the evaluation of prophylactic treatment measures against side effects, outcome research of a certified BC unit, and demonstration of circulating metastasis-initiating cells.

Coordinator

Prof. Dr. Schneeweiss
Gynecology & Medical Oncology

Prof. Herrmann Brenner
Division of Clinical Epidemiology and Aging Research, German Cancer Research Center

Prof. Dr. Barbara Burwinkel
Division of Molecular Epidemiology, German Cancer Research Center

Prof. Jenny Chang-Claude
Unit of Genetic Epidemiology, Division of Cancer Epidemiology, German Cancer Research Center 

Prof. L. Edler, Prof. A. Benner, Dr. W. Werft
Biometric Consulting and Experimental Design

Prof. Dr. Dirk Jäger, Dr. Inka Zörnig, Dr. Niels Halama
Tumor Immunology, NCT

Prof. Dr. Peter Lichter PD Dr. Marc Zapatka  
Division of Molecular Genetics, German Cancer Research Center

Dr. S. P. Luntz
Coordinating Centre for Clinical Trials Heidelberg, Medical Faculty of the Ruprecht Karls University Heidelberg

Prof. Dr. Frederik Marmé 
Dept. Gyn. Oncology / Medical Faculty of University Hospital Mannheim

Prof. Dr. Oliver Mueller 
Dept. of Cardiology, Angiology and Pneumology, Heidelberg University Hospital

Prof. Dr. Andreas Schneeweiss
Dept. of Gynecology & Medical Oncology, NCT/ Heidelberg University Hospital

Prof. Dr. Hans-Peter Sinn
Dept. of Pathology, Heidelberg University Hospital

Prof. Dr. Karen Steindorf
Division of Physical Activity, Prevention and Cancer, German Cancer Research Center 

PD Dr. Albrecht Stenzinger 
Dept. of Pathology, Heidelberg University Hospital  

Prof. Dr. Andreas Trumpp 
Division of Stem Cells and Cancer, German Cancer Research Center

PD Dr. Stefan Wiemann
Division of Molecular Genome Analysis, German Cancer Research Center

Dr. Joachim Wiskemann
Exercise Oncology, NCT/Heidelberg University Hospital

Departments
 

  • Diagnostic Radiology, Heidelberg University Hospital 
  • Hematology, Oncology and Rheumatology, Heidelberg University Hospital
  • Medical Oncology, NCT/ Heidelberg University Hospital
  • NCT Social Services
  • Obstetrics and Gynecology, Heidelberg University Hospital
  • Institute of Pharmacology, Medical Faculty of Heidelberg University
  • Preventive Oncology, NCT/German Cancer Research Center
  • Radiooncology, Heidelberg University Hospital 
  • Surgery, Heidelberg University Hospital

Expand current translational and early clinical trials program to improve personalized treatment of patients with BC and GC e.g.
 

  • Comprehensive assessment of clinical features and biomarkers to identify patients with advanced or metastatic breast cancer for marker driven trials in humans (CATCH study).
  • Integration of high throughput technology platforms and systems biology approaches into translational and clinical trials program to accelerate the development of personalized treatment options.
  • Expansion of early clinical trials program to explore antibodies and small molecules targeting key receptors and pathways in breast and gynecological cancer e.g. HER2, IGFR1, FGFR, cMET, PI3K/AKT/mTOR, MEK, CDKs, PARP and breast cancer stem cell specific pathways.
  • Exploration of immunological approaches targeting the tumor microenvironment e.g. CSF1R-blocking agents, immunocheckpoint blockers, anti-IL10, anti-IL4 and adoptive T cell transfer.
  • Characterization of circulating tumor cells and evaluation of their prognostic and predictive value.
  1. Thewes V, Simon R, Hlevnjak M, Schlotter M, Schroeter P, Schmidt K, Wu Y, Anzeneder T, Wang W, Windisch P, Kirchgäßner M, Melling N, Kneisel N, Büttner R, Deuschle U, Sinn HP, Schneeweiss A, Heck S, Kaulfuss S, Hess-Stumpp H, Okun JG, Sauter G, Lykkesfeldt AE, Zapatka M, Radlwimmer B, Lichter P, Tönjes M. The branched-chain amino acid transaminase 1 sustains growth of antiestrogen-resistant and ERα-negative breast cancer. Oncogene. 2017 Mar 20. doi: 10.1038/onc.2017.32. [Epub ahead of print] (Impact factor 2014: 8.459).
  2. Hennigs A, Riedel F, Marmé F, Sinn P, Lindel K, Gondos A, Smetanay K, Golatta M, Sohn C, Schuetz F, Heil J, Schneeweiss A. Changes in chemotherapy usage and outcome of early breast cancer patients in the last decade. Breast Cancer Res Treat 2016, 160:491-499. (Impact factor 2014: 5.490).
  3. Hofheinz RD, Gencer D, Schulz H, Stahl M, Hegewisch-Becker S, Loeffler LM, Kronawitter U, Bolz G, Potenberg J, Tauchert F, Al-Batran SE, Schneeweiss A.Mapisal Versus Urea Cream as Prophylaxis for Capecitabine-Associated Hand-Foot Syndrome: A Randomized Phase III Trial of the AIO Quality of Life Working Group. J Clin Oncol 2015, 33:2444-9. Epub 2015 Jun 29. (Impact factor 2014: 18.443).
  4. Swain SM, Baselga J, Kim SB, Ro J, Semiglazov V, Campone M, Ciruelos E, Ferrero JM, Schneeweiss A, Heeson S, Clark E, Ross G, Benyunes MC, Cortés J; CLEOPATRA Study Group. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 2015, 372:724-34. (Impact factor 2014: 55.873).
  5. Thewes V, Simon R, Schroeter P, Schlotter M, Anzeneder T, Büttner R, Benes V, Sauter G, Burwinkel B, Nicholson RI, Sinn HP, Schneeweiss A, Deuschle U, Zapatka M, Heck S, Lichter P. Reprogramming of the ERRα and ERα target gene landscape triggers tamoxifen resistance in breast cancer. Cancer Res 2015, 15;75:720-31. (Impact factor 2014: 9.329).
  6. Baccelli I, Stenzinger A, Vogel V, Pfitzner BM, Klein C, Wallwiener M, Scharpff M, Saini M, Holland-Letz T, Sinn HP, Schneeweiss A, Denkert C, Weichert W, Trumpp A. Co-expression of MET and CD47 is a novel prognosticator for survival of luminal breast cancer patients. Oncotarget 2014, 5:8147-60. (Impact factor 2014: 6.359).
  7. Schneeweiss A, Chia S, Hegg R, Tausch C, Deb R, Ratnayake J, McNally V, Ross G, Kiermaier A, Cortés J. Evaluating the predictive value of biomarkers for efficacy outcomes in response to pertuzumab- and trastuzumab-based therapy: an exploratory analysis of the TRYPHAENA study. Breast Cancer Res 2014, 8;16:R73. (Impact factor 2014: 5.490).
  8. Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, Tausch C, Seo JH, Tsai YF, Ratnayake J, McNally V, Ross G, Cortés J. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol 2013, 24:2278-84. (Impact factor 2014: 7.040).
  9. Baccelli I, Schneeweiss A, Riethdorf S, Stenzinger A, Schillert A, Vogel V, Klein C, Saini M, Bäuerle T, Wallwiener M, Holland-Letz T, Höfner T, Sprick M, Scharpff M, Marmé F, Sinn HP, Pantel K, Weichert W, Trumpp A. Identification of a population of blood circulating tumor cells from breast cancer patients that initiates metastasis in a xenograft assay. Nat Biotechnol 2013, 3:539-44. (Impact factor 2014: 41.514).
  10. Madhavan D, Zucknick M, Wallwiener M, Cuk K, Modugno C, Scharpff M, Schott S, Heil J, Turchinovich A, Yang R, Benner A, Riethdorf S, Trumpp A, Sohn C, Pantel K, Schneeweiss A, Burwinkel B.Circulating miRNAs as Surrogate Markers for Circulating Tumor Cells and Prognostic Markers in Metastatic Breast Cancer. Clin Cancer Res 2012, 18:5972-82. (Impact factor 2014: 8.722).

Clinical Activities

Multidisciplinary patient management
 

  • Multidisciplinary out-patient consultation
  • Multidisciplinary in-patient care
  • Three time weekly interdisciplinary tumor boards
  • Treatment according to NCT SOPs and national and international guidelines
  • Interdisciplinary study management


Specific Treatment Options
 

  • Systemic chemo-/ endocrine/ targeted and immunotherapy
  • Preclinical, translational and clinical phase I-IV trials
  • Tumor surgery and reconstruction incl. endoscopic surgery and free flap reconstruction
  • Radiotherapy incl. IORT, IMRT, brachytherapy, particle therapy
  • GEPARSIXTO, a multicenter, randomised phase 2 trial, established carboplatin as a new option for the neoadjuvant therapy of patients with triple-negative early breast cancer (Lancet Oncol 2014).
  • TRYPHAENA, an international, randomised phase 2 safety study, established the cardiac safety of pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer (Ann Oncol 2013, Breast Cancer Res 2014).
  • CLEOPATRA, an international, phase 3 study established pertuzumab, trastuzumab, and docetaxel as a new treatment standard for the first-line treatment of HER2-positive metastatic breast cancer (Lancet Oncol 2013, N Engl J Med 2015).

Preclinical Activities

Established Technologies: See established technologies of above mentioned divisions and working groups (Members & Internal Partners at German Cancer Research Center (DKFZ) and National Center for Tumor Diseases).

  • The branched-chain amino acid transaminase 1 sustains growth of anti-estrogen-resistant and ERα-negative breast cancer (Oncogene 2017).
  • Reprogramming of the ERRα and ERα target gene landscape triggers tamoxifen resistance in breast cancer (Cancer Res 2015).
  • Identification of a population of CTCs from patients with luminal metastatic breast cancer that initiates metastasis in a xenograft assay. Those functional metastasis initiating cells (MICs) express EPCAM, CD44, CD47 and MET (Nat Biotechnol 2013, Oncotarget 2014).