Details

Autor(en) / Beteiligte

• Pixberg, C.
• Zapatka, M.
• Hlevnjak, M.
• Benedetto, S.
• Suppelna, J.P.
• Heil, J.
• Smetanay, K.
• Michel, L.
• Fremd, C.
• Körber, V.
• Rübsam, M.
• Buschhorn, L.
• Heublein, S.
• Schäfgen, B.
• Golatta, M.
• Gomez, C.
• von Au, A.
• Wallwiener, M.
• Wolf, S.
• Dikow, N.
• Schaaf, C.
• Gutjahr, E.
• Allgäuer, M.
• Stenzinger, A.
• Pfütze, K.
• Kirsten, R.
• Hübschmann, D.
• Sinn, H.-P.
• Jäger, D.
• Trumpp, A.
• Schlenk, R.
• Höfer, T.
• Thewes, V.
• Schneeweiss, A.
• Lichter, P.

Titel

COGNITION: a prospective precision oncology trial for patients with early breast cancer at high risk following neoadjuvant chemotherapy

Ist Teil von

• ESMO open, 2022-12, Vol.7 (6), p.100637, Article 100637

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2022

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• COGNITION (Comprehensive assessment of clinical features, genomics and further molecular markers to identify patients with early breast cancer for enrolment on marker driven trials) is a diagnostic registry trial that employs genomic and transcriptomic profiling to identify biomarkers in patients with early breast cancer with a high risk for relapse after standard neoadjuvant chemotherapy (NACT) to guide genomics-driven targeted post-neoadjuvant therapy. At National Center for Tumor Diseases Heidelberg patients were biopsied before starting NACT, and for patients with residual tumors after NACT additional biopsy material was collected. Whole-genome/exome and transcriptome sequencing were applied on tumor and corresponding blood samples. In the pilot phase 255 patients were enrolled, among which 213 were assessable: thereof 48.8% were identified to be at a high risk for relapse following NACT; 86.4% of 81 patients discussed in the molecular tumor board were eligible for a targeted therapy within the interventional multiarm phase II trial COGNITION-GUIDE (Genomics-guided targeted post neoadjuvant therapy in patients with early breast cancer) starting enrolment in Q4/2022. An in-depth longitudinal analysis at baseline and in residual tumor tissue of 16 patients revealed some cases with clonal evolution but largely stable genetic alterations, suggesting restricted selective pressure of broad-acting cytotoxic neoadjuvant chemotherapies. While most precision oncology initiatives focus on metastatic disease, the presented concept offers the opportunity to empower novel therapy options for patients with high-risk early breast cancer in the post-neoadjuvant setting within a biomarker-driven trial and provides the basis to test the value of precision oncology in a curative setting with the overarching goal to increase cure rates. •The COGNITION molecular profiling diagnostic study has been recruiting in Heidelberg since April 2019 (pilot phase).•Evidence-based alterations in early breast cancer potentially increase cure rates by targeted post-neoadjuvant treatment.•Mutational profiles/signatures remain mostly stable, suggesting restricted selective pressure during neoadjuvant treatment.•COGNITION as the basis to develop the multiarm interventional phase II precision oncology therapy trial COGNITION-GUIDE.•COGNITION is one of the first initiatives in the early setting to potentially impact cure rates by molecular-guided therapies.