Temporal trends and regional variability in BRAF and KRAS genetic testing in Denmark (2010–2022): Implications for precision medicine

Author:

Frost Matilde Grupe123ORCID,Jensen Kristoffer Jarlov2,Jimenez‐Solem Espen123,Qvortrup Camilla4,Kuhlmann Tine Plato5,Andersen Jon Lykkegaard6,Høgdall Estrid5,Petersen Tonny Studsgaard13

Affiliation:

1. Department of Clinical Pharmacology Copenhagen University Hospital Bispebjerg Copenhagen Denmark

2. Copenhagen Phase IV Unit (Phase4CPH), Department of Clinical Pharmacology and Center for Clinical Research and Prevention Copenhagen University Hospital Bispebjerg and Frederiksberg Copenhagen Denmark

3. University of Copenhagen, Faculty of Health and Medical Sciences Copenhagen Denmark

4. Department of Clinical Oncology Rigshospitalet Copenhagen Denmark

5. Department of Pathology Herlev Hospital Herlev Denmark

6. Department of Oncology Herlev Gentofte Hospital Herlev Denmark

Abstract

AbstractObjectiveThis study aims to evaluate the developments in the testing of Kirsten Rat Sarcoma viral oncogene homolog (KRAS) and v‐Raf murine sarcoma viral oncogene homolog B1 (BRAF) mutations across different cancer types and regions in Denmark from 2010 to 2022.Study design and settingUsing comprehensive data from the Danish health registries, we linked molecular test results from the Danish Pathology Registry with cancer diagnoses from the Danish National Patient Registry between 2010 and 2022. We assessed the frequency and distribution of KRAS and BRAF mutations across all cancer types, years of testing, and the five Danish regions.ResultsThe study included records of KRAS testing for 30 671 patients and BRAF testing for 30 860 patients. Most KRAS testing was performed in colorectal (78%) and lung cancer (18%), and BRAF testing in malignant melanoma (13%), colorectal cancer (67%), and lung cancer (12%). Testing rates and documentation mutational subtypes increased over time. Reporting of wildtype results varied between lung and colorectal cancer, with underreporting in lung cancer. Regional variations in testing and reporting were observed.ConclusionOur study highlights substantial progress in KRAS and BRAF testing in Denmark from 2010 to 2022, evidenced by increased and more specific reporting of mutational test results, thereby improving the precision of cancer diagnosis and treatment. However, persistent regional variations and limited testing for cancer types beyond melanoma, colorectal, and lung cancer highlight the necessity for a nationwide assessment of the optimal testing approach.

Publisher

Wiley

Reference31 articles.

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2. The path to the clinic: a comprehensive review on direct KRASG12C inhibitors

3. American Society of Clinical Oncology Provisional Clinical Opinion: Testing for KRAS Gene Mutations in Patients With Metastatic Colorectal Carcinoma to Predict Response to Anti–Epidermal Growth Factor Receptor Monoclonal Antibody Therapy

4. Czarska‐ThorleyD European Medicines Agency.Lumykras: Pending EC decision.2021[Referred 23 November 2021]. Available at:https://www.ema.europa.eu/en/medicines/human/summaries‐opinion/lumykras

5. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sotorasib-kras-g12c-mutated-nsclc.

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