Overview
- Patients with early-stage breast cancer (without metastases) who are candidates for preoperative (neoadjuvant) treatment are eligible to participate in the COGNITION study.
- The study comprehensively examines the characteristics of the cancer cells using the latest methods.
- The goal is to identify patients who are at increased risk of recurrence. The aim is to find a suitable, targeted therapy for them. This subsequent therapy takes place within the treatment study (COGNITION-GUIDE).
Study status: The study is currently enrolling patients (recruitment open).
Breast cancer develops due to changes in the DNA of cells in the mammary gland. These mutated cancer cells have different characteristics than healthy cells.
In breast cancer, as well as in other types of cancer, the patterns of molecular changes can vary significantly from person to person and even from one tumor tissue sample to another.
Some of these molecular changes can be specifically targeted for treatment. Drugs that target these changes are called targeted cancer drugs. These drugs preferentially target altered cancer cells and largely spare the body’s healthy cells.
Early-stage breast cancer is often highly treatable. In some cases, however, there is an increased risk that the cancer will return. In such cases, patients usually receive chemotherapy or other drug therapies before surgery. Experts refer to this approach as neoadjuvant therapy. However, not all tumors respond equally well to this type of treatment.
That is why experts in the COGNITION study are examining patients with tumors that respond poorly to neoadjuvant therapy or who have a high risk of recurrence. They want to determine whether individualized, targeted therapy is an option for this patient group. Patients can receive this treatment in a subsequent therapy trial (e.g., COGNITION-GUIDE) in addition to all standard therapies.
The experts examine the characteristics of the tumors comprehensively. Specifically, they use modern molecular biology methods, collectively known as Next-Generation Sequencing (NGS). In this process, the tumor’s DNA is analyzed in parallel across many small segments to identify changes relevant to tumor growth.
The goal is to identify targets and so-called biomarkers for targeted therapies that are precisely tailored to each individual patient’s tumor. This approach is also known as precision oncology. COGNITION is therefore a precision oncology study.
- You can read more about the goals of the COGNITION study researchers in the section “What is the aim of the COGNITION study?”.
- Further information on the companion CATCH study (advanced breast cancer) can also be found on the NCT Heidelberg study website.
What types of cancer are covered by COGNITION?
The COGNITION study is examining patients with breast cancer
- whose disease is in an early—potentially curable—stage (there is no metastasis) and
- who, due to an increased risk of recurrence, are scheduled to receive drug therapy before surgery (neoadjuvant therapy) or
- for whom neoadjuvant therapy has not worked as expected.
To find out what other eligibility criteria apply for patients to participate in the study, please read the section “Who is eligible for the study?”.
COGNITION is the English acronym for “Comprehensive assessment of clinical features, genomics and further molecular markers to identify patients with early breast cancer for enrollment on marker driven trials.”
In other words:
Experts are conducting a comprehensive analysis of clinical characteristics and biomarkers in patients with early-stage breast cancer who are candidates for neoadjuvant therapy. The goal is to identify patients who are at increased risk of recurrence and for whom targeted cancer drugs are an appropriate treatment option.
You can read what this means in detail in the next section.
Objectives of the COGNITION Study
The COGNITION study has the following main objectives:
- To create an individualized profile of tumor characteristics: To this end, important genetic alterations and biomarkers in the patients’ breast cancer cells are examined.
- To support the decision to use targeted therapies: Biomarkers that are important for response to specific treatments help guide the selection.
- To identify who is eligible to participate in further clinical trials: The experts aim to determine which patients are eligible for COGNITION-GUIDE or other studies testing targeted cancer drugs. These treatments are precisely tailored to the individual characteristics of the tumor. The goal is to make the therapy even more effective and to further reduce the risk of relapse.
Patients can participate in the COGNITION study if all of the following criteria are met:
- Patients have early-stage breast cancer, meaning there is no metastasis in other organs. The specific subtype of breast cancer does not matter.
- Patients for whom chemotherapy or another form of drug therapy is planned or has been administered before surgery (neoadjuvant therapy).
- Patients who have already received neoadjuvant therapy may also participate. The prerequisite is that the tumor has responded only partially, or not as desired, to that therapy.
Note: The point at which patients can enroll in the study depends on the stage of their disease. - The patient is over 18 years of age.
- The patient has signed a consent form. This includes consent for sample collection via biopsy or during surgery.
- The patient’s general health is good. This means that the patient can manage their daily life without major limitations.
Patients cannot participate in the study if any of the following criteria apply:
- One of the above criteria is not met.
- The patient has a serious comorbid condition or limitation that precludes participation in the study.
- The breast cancer has already metastasized. For these patients, participation in the CATCH study may be possible.
At what point is participation possible?
Enrollment in COGNITION is possible during neoadjuvant therapy (NAT) and continues through the end of post-neoadjuvant therapy (PNAT). A (neoadjuvant) treatment must have taken place before surgery. The tissue sample (biopsy) can be taken at various times:
- Before the start of neoadjuvant therapy, if such therapy is planned.
- After completion of neoadjuvant therapy, if the tumor has not shown the desired response. Patients can be enrolled, for example, after the last cycle of chemotherapy and before surgery.
- During surgery, a tissue sample of the remaining tumor is collected either as fresh-frozen or as paraffin-embedded material (FFPE).
At the same time, one of the following conditions must apply:
- The breast cancer is HER2-positive, and residual tumor is still detectable. "HER2-positive" means that large amounts of the HER2 protein can be detected on the surface of the breast cancer cells. HER2 transmits growth signals to the cancer cells.
OR - The breast cancer is “triple-negative,” and residual tumor is still detectable. “Triple-negative” means that the breast cancer cells have no binding sites for the female sex hormones estrogen and progesterone (i.e., they are hormone receptor-negative) and do not express HER2 on their surface.
OR - The breast cancer is hormone receptor-positive but HER2-negative. In addition, tumor remnants are still present, and doctors assess the risk of recurrence as high (classified with a CPS-EG score of at least 3).
OR - The breast cancer is hormone receptor-positive but HER2-negative. Tumor residue is still detectable, the lymph nodes are involved, and the CPS-EG score is at least 2.
The COGNITION study is a:
- Multicenter study: Patients can participate at various NCT study centers in Germany.
- Registry study: Scientific data and information about patients are collected by analyzing their tumors. The aim is to develop individualized treatment strategies whenever possible.
(1) Registration and Informed Consent
The patient registers for a consultation at the study center. There, the study physicians assess whether an analysis of the tumor genome could be beneficial.
During the first consultation, the patient learns about the study’s objectives, the potential benefits of participation, and any risks involved. This serves as an opportunity to ask questions about the nature of the study as well as about the specific procedures involved. If patients decide to participate after this discussion, they must sign a written informed consent form.
(2) Tissue and blood sample collection
A fresh and well-preserved tissue sample is required for the examination of the tumor tissue.
- Tissue is usually collected via a biopsy before NAT and, if a residual tumor is present after NAT, after NAT or before surgery.
- If no fresh tissue can be obtained (before or after NAT), paraffin-embedded material (FFPE) from the standard surgical procedure can also be analyzed.
- A pathologist then examines the sample under a microscope to determine whether there are enough tumor cells in the tissue to ensure that the analysis can be performed reliably.
In addition, a blood sample is collected. The genetic material from the white blood cells in the sample is used as a healthy control. This helps identify changes in the cancer cells that are specific to the tumor.
(3) Molecular genetic testing
Genetic information (see DNA and RNA) is extracted from the tissue and blood samples and analyzed using modern testing methods.
Experts compare the characteristics of the tumor with those of the same person’s healthy cells.
This allows for the identification of molecular changes in the tumor that may be suitable for treatment with specific medications (targeted cancer drugs).
(4) Discussion at the molecular tumor board
Based on the data obtained and further laboratory tests, potential targets within the tumor cells are identified that can be used to make a treatment recommendation as part of the Phase 2 COGNITION-GUIDE study.
A team of experts from various disciplines meet regularly in what is known as a molecular tumor board to discuss and evaluate the results.
- Participants include physicians as well as specialists in bioinformatics, molecular biology, and human genetics.
- Based on the identified alterations (biomarkers), they create a ranking of potential targeted therapies and document them in a report.
- The results help identify personalized therapies for the patient.
(5) Treatment Recommendations and Implementation of Treatment Options
The study physician discusses the results of the examination and the recommendations of the molecular tumor board with the patient during a consultation. The treating oncologists also receive the corresponding report.
The treatment proposed by the molecular tumor board is then administered—subject to the participant’s consent—as part of the COGNITION-GUIDE therapy trial or another clinical trial. All patients undergo routine clinical examinations at regular intervals.
(6) Follow-up
Patients in the COGNITION study, or the COGNITION-GUIDE, are followed up for a maximum of 10 years.
Every 6 months, and whenever there is a change in treatment, the treating physicians collect data on the disease and further treatment.
The data collected during the follow-up phase will be scientifically analyzed. It will be used to assess the efficacy and safety of the treatment over a longer period of time and to evaluate the study’s objectives.
These are the potential benefits of participating in the COGNITION study:
- Patients can benefit from modern precision oncology approaches. These make it possible to specifically search for treatment options tailored to the individual characteristics of the tumor cells and the patient’s disease status.
- The individual disease situation is discussed and evaluated by specialists from various disciplines across multiple study sites. Such a discussion is also known as a molecular tumor board.
- Patients have the opportunity to receive a treatment recommendation that is tailored (personalized) to their cancer.
- The proposed therapy could improve the patients’ prognosis and reduce their risk of recurrence and metastasis.
- Based on the analysis, participants may have the opportunity to be treated with a targeted therapy in a clinical trial (COGNITION-GUIDE).
- Patients can decide in advance whether they would like to be informed about a genetic predisposition to cancer. If a possible genetic predisposition is identified, they or their family members have the option of receiving genetic counseling to potentially take preventive measures.
However, participation in the COGNITION study may also have disadvantages:
- Sample collection, which generally takes place as part of routine procedures, carries minor risks. These include, for example, post-procedural bleeding or inflammation.
- Despite comprehensive data protection and high data security, there remains a small residual risk of re-identification. This means that it is possible to identify a specific patient based on their genetic data. To ensure the highest possible level of data security, special data protection measures have been developed so that all personal data is stored only in an encrypted form.
Where is the study being conducted?
Patients can participate in the COGNITION trial at the corresponding NCT sites.
The addresses and contact information for the study centers are as follows:
Heidelberg
National Center for Tumor Diseases (NCT) Heidelberg
Prof. Dr. Andreas Schneeweiss
Phone: 06221 56 5959
E-mail: Patientenzentrum2.NCT@med.uni-heidelberg.de
Augsburg
Augsburg University Hospital | Department of Obstetrics and Gynecology
Prof. Dr. Nina Ditsch
Phone: 0821 400 2208
E-mail: studien.gyn@uk-augsburg.de
Berlin
Charité – Berlin University Medical Center, Department of Gynecology, including the Breast Center CCM/CBF
Prof. Dr. Jens-Uwe Blohmer
Phone: 030 450 664485
E-mail: brustzentrum-studienzentrum@charite.de
Dresden
Carl Gustav Carus University Hospital at TU Dresden | Department of Obstetrics and Gynecology
Prof. Dr. Pauline Wimberger
Phone: 0351 458 4223
E-mail: studiensekretariat.gyn@ukdd.de
Erlangen
Friedrich-Alexander University of Erlangen-Nuremberg, Erlangen University Hospital | Department of Obstetrics and Gynecology
Prof. Dr. Peter Fasching
Phone: 09131 85 33572
E-mail: fk-studienzentrale@uk-erlangen.de
Cologne
Department of Gynecology and Gynecologic Oncology
Dr. Christian Maurer
Phone: 0221 478 89213
E-mail: Frauenklinik-Studienzentrale-at-uk-koeln.de
Regensburg
Department of Obstetrics and Gynecology at the University of Regensburg, Caritas St. Josef Hospital
PD Dr. Stephan Seitz
Phone: 0941 782 7512
E-mail: FHK-Studienzentrum@csj.de
Stuttgart
Robert Bosch Hospital Stuttgart, Department of Gynecology and Obstetrics
Robert Bosch Center for Tumor Diseases
Prof. Dr. Matthias Schwab
Phone: 0711 8101 7761
E-mail: NCT-Studienzentrale@rbk.de
Tübingen
Tübingen University Hospital | Department of Women’s Health
Prof. Dr. Andreas Hartkopf
E-mail: studienzentrale.fr@med.uni-tuebingen.de
Ulm
University Hospital Ulm | Department of Obstetrics and Gynecology
Prof. Dr. Wolfgang Janni
Phone: 0731 500 58529
E-mail: studienzentrale.ufk@uniklink-ulm.de
Würzburg
University Hospital Würzburg | Department of Obstetrics and Gynecology
Prof. Dr. Achim Wöckel
E-mail: Studien_FK@ukw.de
What costs will participants incur?
Participation in the study is free of charge for patients. However, you will not receive any compensation for your time or expenses. Travel expenses are not reimbursed as part of the study.
If you have any questions about the study’s funding, you can ask the study team, for example during the informational meeting.
How many participants will the study accept? Are there still places available?
You can find out whether participation is possible by contacting the respective NCT study centers.
If you are interested in the study, patients or their treating physicians can send the treatment documents by mail or email to the nearest NCT study center. These include the:
- most recent doctor’s letter
- results from the tissue examination and imaging studies
- surgical report
- tumor board recommendation
- patient’s contact information (including a phone number)
- referral form
The COGNITION study is supported by representatives from the following patient organizations:
- Mamma Mia! – The Breast Cancer Magazine
- Breast Cancer Germany e.V.
- PATH Foundation – Patients’ Tumor Bank of Hope
Those interested can find more information about the COGNITION study on the study website, the NCT Heidelberg website, and at the following links:
- Flyer on the CATCH and COGNITION studies (PDF | German)
- Cancer guide “Mamma Mia!” – Precision Oncology (PDF | German)
- Explanatory video on the COGNITION study
Scientific publications (selection)
- Pixberg, C., Zapatka, M., Hlevniak, M. et al. COGNITION: a prospective precision oncology trial for patients with early breast cancer at high risk following neoadjuvant chemotherapy. ESMO Open 7, 100637 (2022). https://doi.org/10.1016/j.esmoop.2022.100637
- Pixberg C, Maurer C, Smetanay K, Straßl L, Hlevnjak M, Zapatka M, Wagner CV, Yazdanparast H, Kurzawa J, Erben V, Schneeweiss A. et al. COGNITION-GUIDE - Genomics-Guided Targeted Post-Neoadjuvant Therapy in Patients with Early Breast Cancer: Study Design of a Multicenter, Open-Label, Umbrella Phase II Study. Geburtshilfe Frauenheilkd. 2025 Apr 10;85(6):611-619. doi: 10.1055/a-2557-1876
This study description was prepared by authors from the Cancer Information Service, under the direction of Dr. S. Weg-Remers, based on the study documentation.