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

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 wi...

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Published in:	ESMO open Vol. 7; no. 6; p. 100637
Main Authors:	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.
Format:	Journal Article
Language:	English
Published:	England Elsevier Ltd 01-12-2022 Elsevier
Subjects:	Antineoplastic Combined Chemotherapy Protocols - therapeutic use Breast Neoplasms - drug therapy Breast Neoplasms - genetics Breast Neoplasms - pathology curative precision oncology early breast cancer Female Humans molecularly targeted therapy Neoadjuvant Therapy Neoplasm Recurrence, Local - drug therapy Original Research Precision Medicine prospective precision oncology trial Prospective Studies tumor evolution early breast cancer prospective precision oncology trial tumor evolution curative precision oncology molecularly targeted therapy
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Summary:	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.
Bibliography:	These authors contributed equally.
ISSN:	2059-7029 2059-7029
DOI:	10.1016/j.esmoop.2022.100637