COGNITION (eBC) und CATCH (mBC)

Breast cancer: Diagnostic Platforms

  • integrative biomarker-driven personalised therapy based on the individual genetic profile of the tumor
  • in addition to conventional characteristics (e.g. histological markers), prognostic and predictive markers, the individual genomic tumor biology and biomarker profile supports therapy decisions
  • depending on their tumor stage breast cancer patients can be allocated to two different diagnostic-platforms: COGNITION (early breast cancer) or CATCH (advanced-stage / metastatic breast cancer

 

Overview of breast cancer-specific platforms

  COGNITION (eBC) CATCH (mBC)
Indication

Early breast cancer that can be treated with curative intention with indication for neoadjuvant therapy (regardless of subtype)
and patients with poor response to neoadjuvant therapy

Metastatic breast cancer at the time of diagnosis or progression
Material requirement

Native material (fresh-frozen)

a) baseline (before neoadjuvant therapy)
b) time of surgery (after neoadjuvant therapy)
+blood

Native material (fresh-frozen):

metastatic lesion (biopsy + surgical material) +blood
Method profiling
(Illumina)
 
  • whole genome /exome sequencing
  • transciptome sequencing (polyA,)
  • validation of selected therapeutic target targets
 
 
  • whole genome/ exome sequencing
  • transcriptome sequencing (polyA, )
  • validation of selected therapeutic targets
 




COGNITION

Comprehensive assessment of clinical features, genomics and further molecular markers to identify patients with early breast cancer for enrolment on marker driven trials: early high-risk breast carcinoma.

COGNITION aims to offer a comprehensive molecular-genetic profiling of the therapy-resistant lesion after neoadjuvant therapy for early high-risk breast cancer patients who present with a residual bulk tumor (non-pCR or high CPS-EG score) after neoadjuvant therapy. This approach allows for an individualised, risk-adapted, biomarker-stratified therapy recommendation following standard post-neoadjuvant therapy in order to decrease the substantial risk of recurrence and metastasis.

 

Neoadjuvant chemotherapies (NACT) represent the cornerstone of treating Luminal B, HER2 positive and Triple Negative breast cancer. The pathological Complete Response (pCR) and the CPS-EG score serve as solid intermediate endpoints and surrogate markers for overall survival and enable identification of patients with a high risk of recurrence. Post-neoadjuvant trials such as the CREATE-X and the KATHERINE already underlined the potential of intensified postneoadjuvant chemotherapy to lower the risk for relapse. We hypothesize that high-risk patients benefit from an individualized therapy following surgery and standard-post-neoadjuvant therapy adjusted according the molecular profile of their invasive residual tumor to decrease the risk of recurrence and especially distant metastases.

Within COGNITION, precision oncology for high-risk breast cancer patients is implemented in daily clinical practice. Within the framework of the study, a comprehensive molecular diagnostics (predominantly high-throughput sequencing) is applied for high-risk patients to generate a comprehensive genotype and biomarker analysis of the individual tumor.

For this purpose, primary tumors prior to neoadjuvant therapy as well as the residual tumor after neoadjuvant therapy at the time of surgery are analysed by molecular profiling (especially whole-genome / whole-exome and transcriptome sequencing) for a differentiated adequate diagnosis to stratify the post-neoadjuvant treatment according to its genomic patterns. This strategy empowers therapy escalation (in addition to the standard) during the prospectively linked phase II interventional trial (COGNITION-GUIDE) with targeted substances. COGNITION-GUIDE is currently planned and will be available soon (see below) in order to access if precision oncology in the curative setting can lower the substantial risk of disseminated metastasis and hence to increase cure rates.

Inclusion criteria:

  • Patients with histological confirmed early breast cancer who are treated with curative intention (Stage I-III) and who have an indication for neoadjuvant therapy (all subtypes)
  • Patients who do not response to neoadjuvant therapy (inclusion prior to surgery to extract fresh tissue for the tumor genome sequencing is essential)
  • Possibility for tissue (biopsy) and blood sampling or, in case of no response, FFPE surgery material with a content of tumor cells of >20 %

Exclusion criteria:

  • metastatic breast cancer
  • Inadequate organ function
  • ECOG >1
  • Impossibility of tissue / blood sampling

The diagnostic platforms follow a standardised workflow:



1. Information / enrolment at the NCT Heidelberg or any other participating study center

2. Acquisition of biomaterial (tissue + blood) for molecular analyses in the course of standard routine procedures or as a study specific measure

  • Tumor tissue: Fresh tissue samples (no FFPE if possible) as pre-requesite for downstream molecular-genetic analyses
  • Blood withdrawal (comparative sample of normal body cells to define tumor-specific genetic alterations)

3. Evaluation tumour cell content fresh tissue sample (minimum content 20 % tumor cells) and tumor infiltrating lymphocytes

4. Molecular Analyses: Tumor-Genome-Sequencing (DKFZ Heidelberg) / Next Generation Sequencing

  • Analyte-Isolation (DNA, RNA, Protein, Sample Processing Lab, DKFZ)
  • Sample preparation for high-throughput sequencing (Genomics Core Facility, DKFZ)
  • Method: whole-genome/ whole-exome and transcriptome sequencing

5. Discussion of molecular-genetic findings within the interdisciplinary molecular tumor board

  • Participants: Oncologists, bioinformaticians, molecular biologists, pathologists, human geneticists
  • Prioritisation of therapy-relevant gene alterations and molecular targets
  • Generating a therapy plan combined in a molecular report

6. Discussion of molecular-genetic findings and consideration of possible treatment options with the patient

Contact

Tel.: 06221 56-5959 or 06221 56-7985
E-Mail: Patientenzentrum2.nct@med.uni-heidelberg.de

 

Coordination

The diagnostic trials are carried out in close cooperation between the University Hospital, the German Cancer Research Center (DKFZ) and the Molecular Diagnostics Program at NCT Heidelberg.



CATCH

Comprehensive assessment of clinical features and biomarkers to identify patients with advanced or metastatic breast cancer for marker driven trials in humans)

Precision oncology study: Molecular diagnostics for stratifying therapy of metastasised breast cancer patients

CATCH aims to create an individual genotype and biomarker profile of prognostically leading lesions for patients with advanced metastasised breast cancer by using genome-wide high-throughput tumor genome sequencing.

By employing this strategy, prognostic and predictive markers, therapy-relevant driver mutations and biomarkers are identified to optimise the treatment decision for targeted substances.

Treatment outside of the register study occurs in (1) independent phase I-III clinical studies, (2) in the licenced indication or as (3) off-label use.

Therapeutic resistance towards conventional therapy is especially attributed to high intra- and inter-tumoral heterogeneity. Furthermore, nowadays only a limited amount of targeted substances for advanced breast cancer is available and diagnostic procedures routinely do not contain comprehensive biomarker evaluation.

Strategy:

Within the CATCH study predictive biomarkers and drug targets are evaluated using integrative comprehensive tumor genome analysis (whole-genome and transcriptome sequencing). Within the register study all procedures, from inclusion to biomaterial extraction to prioritising targeted therapies, are implemented in clinical practice. With the gained biological information, the practising oncologist at NCT is able to identify patients who profit from innovative targeted treatment modalities.

Treatment occurs at the discretion of the practising oncologist 1) within independent Phase I/-IV AMG studies, 2) in the authorised indication or (3) as off-label use.

Endpoints:

PFS2 / PFS2 Ratio: Progression-free survival (PFS) during molecular stratified therapy in comparison to PFS during immediately preceding standard therapy of the individual patient

Inclusion criteria:

  • mBC patients (all subtypes) after initial diagnosis or at the time of progression
  • life expectancy > 6 months
  • ECOG ≤ 2
  • Possibility to extract fresh tissue of the leading prognostic lesion

Exclusion criteria:

  • Impossibility to extract fresh tissue

The diagnostic platforms follow a standardised workflow:



1. Information / enrolment at the NCT Heidelberg or any other participating study center

2. Acquisition of biomaterial (tissue + blood) for molecular analyses in the course of standard routine procedures or as a study specific measure

  • Tumor tissue: Fresh tissue samples (no FFPE if possible) as pre-requesite for downstream molecular-genetic analyses
  • Blood withdrawal (comparative sample of normal body cells to define tumor-specific genetic alterations)

3. Evaluation tumour cell content fresh tissue sample (minimum content 20 % tumor cells) and tumor infiltrating lymphocytes

4. Molecular Analyses: Tumor-Genome-Sequencing (DKFZ Heidelberg) / Next Generation Sequencing

  • Analyte-Isolation (DNA, RNA, Protein, Sample Processing Lab, DKFZ)
  • Sample preparation for high-throughput sequencing (Genomics Core Facility, DKFZ)
  • Method: whole-genome/ whole-exome and transcriptome sequencing

5. Discussion of molecular-genetic findings within the interdisciplinary molecular tumor board

  • Participants: Oncologists, bioinformaticians, molecular biologists, pathologists, human geneticists
  • Prioritisation of therapy-relevant gene alterations and molecular targets
  • Generating a therapy plan combined in a molecular report

6. Discussion of molecular-genetic findings and consideration of possible treatment options with the patient

Contact

Tel.: 06221 56-5959 or 06221 56-7985
E-Mail: Patientenzentrum2.nct@med.uni-heidelberg.de

 

Coordination

Prof. Dr. Lichter
Molecular Genetics, DKFZ

 
 
 

The diagnostic trials are carried out in close cooperation between the University Hospital, the German Cancer Research Center (DKFZ) and the Molecular Diagnostics Program at NCT Heidelberg.

Further Clinical Trials

The Division of Gynecological Oncology conducts numerous further diagnostic, treatment, observational and clinical trials.

»You can find an overview under "Clinical trials".