Circulating HER2 DNA after Trastuzumab Treatment Predicts Survival and Response in Breast Cancer

Background: Only a subset of breast cancer patients responds to the HER2 inhibitor trastuzumab, and methods to identify responders are needed. Patients and Methods: We studied 28 patients with metastatic breast cancer that had amplified human epidermal growth factor receptor 2 (HER2) genes in their primary tumour and were treated with a combination of trastuzumab and chemotherapy. Plasma was collected and amplification of the HER2 gene in circulating DNA and the amounts of the extracellular domain (ECD) of HER2 were measured just before first treatment (n=28) and just before second treatment three weeks later (HER2 DNA (n=22), HER2 ECD (n=23)). Results: Pretreatment levels of HER2 gene amplification and HER2 ECD did not correlate to clinical parameters. However, 9 out of 22 patients had a more than a 14% (2 x SD) reduction in HER2 gene amplification following treatment and showed improved response (p=0.02), and overall survival (p=0.05). HER2 ECD kinetics did not correlate to clinical data. Conclusion: We suggest that a decrease in HER2 gene amplification in the plasma predicts a more favourable response to trastuzumab.