Plasma‐based analysis of ERBB2 mutational status by multiplex digital PCR in a large series of patients with metastatic breast cancer

• Published in: Molecular oncology Vol. 18; no. 11; pp. 2714 - 2729
• Main Authors: Corné, Julien, Quillien, Véronique, Godey, Florence, Cherel, Mathilde, Cochet, Agathe, Le Du, Fanny, Robert, Lucie, Bourien, Héloïse, Brunot, Angélique, Crouzet, Laurence, Perrin, Christophe, Lefeuvre‐Plesse, Claudia, Diéras, Véronique, De la Motte Rouge, Thibault
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-11-2024; FEBS Press; John Wiley and Sons Inc; Wiley
• Series: Molecular Oncology
• Subjects: Biopsy; Breast Cancer; Breast carcinoma; Cancer; circulating tumor DNA; Endocrine therapy; Epidermal growth factor; ErbB-2 protein; ERBB2; Estrogens; Genetic testing; Kinases; Life Sciences; Liquid Bioposies; liquid biopsies; Medical prognosis; Metastases; Metastasis; metastatic breast cancer; multiplex digital PCR; Mutation; Mutation rates; Online data bases; Patients; PCR‐Based Techniques; Plasma; Plasma Cells; Polymerase chain reaction; Protein-tyrosine kinase receptors; Tumors; United States > US; multiplex digital PCR; plasma; liquid biopsies; ERBB2; metastatic breast cancer; circulating tumor DNA
• ISSN: 1574-7891; 1878-0261; 1878-0261
• DOI: 10.1002/1878-0261.13592

Erb‐b2 receptor tyrosine kinase 2 (ERBB2)‐activating mutations are therapeutically actionable alterations found in various cancers, including metastatic breast cancer (MBC). We developed multiplex digital PCR assays to detect and quantify ERBB2 mutations in circulating tumor DNA from liquid biopsies. We studied the plasma from 272 patients with hormone‐receptor‐positive, human epidermal growth factor receptor 2‐negative (HR+/HER2−) MBC to detect 17 ERBB2 mutations using a screening assay. The assay was developed on the three‐color Crystal dPCR™ naica® platform with a two‐step strategy for precise mutation identification. We found that nine patients (3.3%) harbored at least one ERBB2 mutation. The mutation rate was higher in patients with lobular histology (5.9%) compared to invasive breast carcinoma of no special type (2.6%). A total of 12 mutations were found with the following frequencies: L755S (25.00%), V777L (25.00%), S310Y (16.67%), L869R (16.67%), S310F (8.33%), and D769H (8.33%). Matched tumor samples from six patients identified the same mutations with an 83% concordance rate. In summary, our highly sensitive multiplex digital PCR assays are well suited for plasma‐based monitoring of ERBB2 mutational status in patients with MBC.
Erb‐b2 receptor tyrosine kinase 2 (ERBB2)‐activating mutations are therapeutically actionable alterations found in various cancers, including metastatic breast cancer (MBC). We developed highly sensitive multiplex digital PCR assays to detect and quantify ERBB2 mutations in circulating tumor DNA from liquid biopsies and found mutations in 3.3% of 272 patients with hormone‐receptor‐positive, human epidermal growth factor receptor 2‐negative (HR+/HER2−) MBC.