In recent years, numerous novel targeted drugs against breast cancer have been developed because of the rapid progress in multigene molecular testing based on next-generation sequencing (NGS). However, it is a great challenge for clinicians to update the drug information timely, therefore necessitating that clinical laboratories provide adequate and comprehensive targeted drugs information to clinicians as a reference. The premise of providing this information is the accuracy of variant detection. Our study aimed to assess the entire process of variant detection, interpretation, and targeted therapy.
Laboratories were instructed to use routine methods for variant detection. The results were evaluated based on a predefined score system, and differences in variant interpretation were analyzed. Targeted drug information provided by laboratories was also summarized, and its accuracy and sufficiency were assessed.
Overall, 90.1% (82/91) of the laboratories produced accurate results. 78.9% (15/19) of the errors were false positives or false negatives. Incorrect and insufficient drug information was mainly provided due to failure in timely database updating, inconsistencies with the detected mutations or given clinical information, and negligence during phase I clinical trials. To prioritize providing targeted drug information, laboratories collected data were based on different factors, including variant clinical significance, allele frequency, and variant positions in the signal pathway.
The variant detection capability was satisfactory, but the ability to provide accuracy and comprehensive targeted drug information should be urgently improved. Our study summarized a completed NGS-based multigene molecular detection pipeline, aiming to better inform precision treatment for breast cancer patients.
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Supplementary Fig. 1. Performance of the 91 participating laboratories. The distribution of results is indicated by the columns of samples between the darkest vertical lines. A green box indicates a concordant result; a purple box indicates a false-negative result; a yellow box indicates a false-positive result; a red box indicates a mutation error; a pink box means a nomenclature error; and a gray box indicates no response was required, because a variant fell outside the specific detectable range. The variant allele frequencies reported are shown inside the boxes
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Zhang, R., Gao, P., Ding, J. et al. Assessment of significant procedures in multigene molecular detection for breast cancer in clinical laboratories: from variant detection to targeted therapy. Breast Cancer 27, 111–121 (2020) doi:10.1007/s12282-019-01000-2
- Multigene molecular detection
- Variant interpretation
- Targeted drug
- Breast cancer