Clinicopathological characteristics of HER2-positive metastatic colorectal cancer and detection of HER2 in plasma circulating tumor DNA

Abstract Background Therapy targeting human epidermal growth factor receptor 2 ( HER2 , also known as ERBB2 ) is an effective approach for HER2 –positive metastatic colorectal cancer (mCRC). HER2 status is typically determined using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). Circulating tumor DNA (ctDNA) enables non-invasive detection of gene mutations and copy number alterations including HER2 amplification. Materials and Methods We screened 351 patients with metastatic CRC and studied the clinicopathological characteristics of HER2 –positive mCRC. HER2 expression in tumor samples measured with IHC and FISH was compared with HER2 copy number variation (CNV) in plasma ctDNA detected by targeted sequence capture covering exons of 170 genes. We also examined the correlation between changes in tumor burden in ctDNA and antitumor response by imaging evaluation during the treatment course. Results Positive HER2 status was observed in 12 (3.4%) patients (7 males and 5 females) with median age of 56 years. The HER2 concordance rate between tumor samples and ctDNA was 66.7% (20/30). Changes in tumor burden in ctDNA during the treatment course correlated with responses on imaging. Conclusions Detection of HER2 CNV in ctDNA may be an alternative option for non-invasive determination of HER2 status. Tumor burden changes in ctDNA were consistent with imaging evaluation.