Measurement of HER2 copy number from tissue and ctDNA in cancer
Research type
Research Study
Full title
Development of droplet digital PCR measurement of HER2 copy number from tissue samples and ctDNA in cancer patients
IRAS ID
303002
Contact name
Guy Chung-Faye
Contact email
Sponsor organisation
King’s College Hospital NHS Foundation Trust
Clinicaltrials.gov Identifier
N/A, N/A
Duration of Study in the UK
2 years, 0 months, 1 days
Research summary
The human epidermal growth factor receptor-2 gene (HER2, also known as ERBB2) is a proto-oncogene that is located on chromosome 17q21. Amplification and overexpression of HER2 are detected in approximately 15–20% of breast tumours and 15% of gastric tumours. HER2/ERBB2 amplification detection assays are widely used as companion diagnostic tools for Herceptin targeted therapy on Breast and Gastric cancer patients.
Growing clinical evidence indicates the potential of circulating cell-free tumour DNA (ctDNA) as a reliable cancer biomarker for early diagnostics and prognosis. The presence/absence or level of HER2 in ctDNA is correlated with patient’s response to targeted therapy and disease development, supporting the necessity of a liquid biopsy assay for HER2 amplification. Sensitive detection of HER2 in ctDNA would enable effective therapeutic management of cancer patients in a personalized manner.
Current tests approved for clinical use are either IHC or FISH, and could only be used on tissue samples. Moreover, these conventional methods have some limitations owing to the inherent tumour biological heterogeneity resulting in ambiguous results, and the dependency on the evaluator’s subjectivity. Hence, new technique is warranted to improve test accuracy and sensitivity.
Droplet digital PCR (ddPCR) is an alternative technique to achieve a higher throughput capability and may yield a more accurate diagnosis for HER2 amplification by generating digital resolution. It has been reported to show good HER2 status concordance between ddPCR assays and standard assays.
The fundamental aims are 1) develop and validate ddPCR assay for HER2 status assessment using DNA from diagnostic tissue samples from breast and gastric cancer patients, 2) establish a method of monitoring HER2 status using ctDNA in cancer patients.
The current project will enable us to move beyond or supplement traditional HER2 IHC and FISH testing in enriching patients for HER2-targeted therapy and monitoring disease progression.REC name
London - Central Research Ethics Committee
REC reference
22/PR/0454
Date of REC Opinion
11 May 2022
REC opinion
Further Information Favourable Opinion