Quantification of Cell-free HER-2 DNA in Plasma from Breast Cancer Patients: Sensitivity for Detection of Metastatic Recurrence and Gene Amplification

• Main Authors: Patricia Diana Sørensen, Rikke Fredslund Andersen, Niels Pallisgaard, Jonna Skov Madsen, Erik Hugger Jakobsen, Ivan Brandslund
• Format: Article
• Language: English
• Published: AboutScience Srl 2015-08-01
• Series: Journal of Circulating Biomarkers
• Subjects: breast cancer; cell-free DNA; gene amplifica‐ tion; HER-2; metastatic recurrence; sensitivity
• Online Access: http://www.intechopen.com/journals/journal-of-circulating-biomarkers/quantification-of-cell-free-her-2-dna-in-plasma-from-breast-cancer-patients-sensitivity-for-detectio

The purpose of this study was to quantify the free-circu‐ lating plasma HER-2 DNA (cfHER-2 DNA) and to assess the ability of analysis to discriminate between patients with primary breast cancer and healthy controls in order to detect metastatic recurrence in comparison with serum HER-2 protein and also HER-2 gene amplification. The study population consisted of 100 patients with primary breast cancer and 50 healthy female donors. An additional 22 patients with metastases were subsequently included. cfHER-2 DNA was quantified with a quantitative PCR method together with a reference gene. Results: Using a cut-off of 2.5 for the ratio of the cfHER-2 DNA/reference gene, three (of 15) tissue HER-2-positive patients had a ratio >2.5 prior to the detection of metastatic disease. In the post-metastatic/pre-chemotherapy setting, 11 (of 23) tissue HER-2-positive patients with metastases had a ratio >2.5. There was no difference between absolute preoperative cfHER-2 DNA values for patients with primary breast cancer and those for healthy controls. There was no difference between cfHER-2 DNA values taken within nine months of development of the metastatic disease and the levels in patients without metastases, but there was a significant difference in the corresponding serum HER-2 protein levels in the tissue HER-2-positive patient group. Conclusion: Amplified HER-2 DNA can be detected in plasma when using a ratio between cfHER-2 DNA and a reference gene. cfHER-2 DNA could not be used to dis‐ criminate between patients with primary breast cancer and healthy controls, and could not predict the development of metastatic disease.