Research Projects of the German Breast Group

In order to better understand the reasons and the dynamics of breast cancer, the GBG established an advisory subboard for translational research. Its members are researchers engaged to optimize clinical routines based on recent research results – from bench to bedside and back. The overall aim is to customize treatments to individual patients.

The GBG initiates dozens of translational research projects each year and publishes their results. They all address current scientific questions of clinical relevance. Most of them achieve high impact points; this success is based on the cooperation with partners of high expertise, inclusion of different specialists, direct communication within the teams, continuity in breast cancer research, and the combination of high-quality clinical and biomarker data.

Our translational research projects cover a wide range:

• from new clinical variables to single biomarkers of special interest to huge numbers of biomarker variables
• biomarkers from different biomaterial
  
  • such as tumor biopsies, resections, or blood
  • before or after certain treatment phases

• biomarkers from very different methods like IHC, PCR, WGS/WES, expression profiling, FACS, image analysis/machine learning, and many more
• analyses within a specific GBG study and multi-study pooled analyses
• with academic partners and commercial pharmaceuticals and diagnostics partners

New ideas for patient-oriented and innovative research are welcome: Translational research

The German Cancer Consortium (DKTK) is a long-term, joint initiative involving the German Federal Ministry of Education and Research (BMBF), participating German states and the DKFZ (German Cancer Research Center). The main aim of the DKTK is to discover, develop, test and apply new personalized oncology strategies. As an external partner of the DKTK the GBG supports collaborative translational research projects with biomaterial samples, its associated clinical data and statistical evaluations. For these studies biomaterial from the trials GeparDuo, GeparTrio, GeparQuattro, GeparQuinto, GeparSixto, GeparSepto, BCP and others has been used.

The TransLUMINAL-B project in 2016-2018 evaluated new diagnostic and therapeutic strategies in high-risk luminal breast cancer. The main aims of the project were

1. to identify molecular alterations and key regulators driving the metastatic program by analysis of CTCs, DTCs and MICs ex vivo and in cell culture models
2. to characterize RTCs after neoadjuvant therapy, and
   
3. to reverse-translate and validate the uncovered molecular alterations, signaling pathways and metastatic programs in PDX models and large cohorts from clinical trials to provide a clinically relevant risk stratification.

The GBG collaborated with other TransLUMINAL-B partners in seven subprojects (publications) and incorporated biomaterial from 11 of its studies.

The project funded by the Deutsche Krebshilfe will conduct parallel analyses of therapy-induced dynamic changes in sequential tumor samples from clinical trials and tumor organoid cultures at the single-cell level. The project consortium includes several academic and one commercial partners from Germany. The adaptation of tumor cells will be monitored with unprecedented resolution: This will enable to define biomarkers related to therapy response and adaptive resistance that will directly inform clinical trials and provide the basis for new therapeutic strategies.

The ONCOBIOME project, funded by the EU and coordinated by Institut Gustave Roussy, analyzes the relationship between gut onco-microbial signatures (GOMS) and the incidence, prognosis and resistance to treatment (and toxicity of this) in cancers of breast, colon, lung and melanoma. The GBG will collect pre-treatment stool samples as part of its GeparTreize study to analyze how GOMS are associated to the response to immune checkpoint blockers. Known predictive approaches (standard clinical variables, additional IHC markers, tumor-infiltrating lymphocytes, immunoscore from the Responsify project, WES, RNA-seq …) will be refined by connecting tumor-derived immune markers as well as microbiome-derived markers.