Biological Monitoring of HER-2 Positive Patients Using Serum HER-2 and Circulating Tumor Cells

摘要

Development of anti-HER-2 therapy (trastuzumab) has been a major advance in breast cancer. The role of tissue and blood biomarkers in predicting response to trastuzumab is relatively unexplored. Our study shows no significant correlation with HER2 dopy number and response (mean 6.25 vs 5.6 copies/Chl7). We postulate that once selected for HER2 amplification, copy number does not influence response to therapy. HER2 extracellular domain (ECD) was present in 24/47 (51%) HER2+ metastatic breast cancer patients and correlated with visceral disease (p=0.018). ECD levels declined in all patients receiving trastuzumab, however the slope of decline in was shallower in progressing patients (ROC 0.89) . We conclude that the utility of this biomarker in predicting response to trastuzumab therapy remains to be established. Circulating tumor cells (CTCs) were found in 44% of HER2 positive metastatic breast cancer patients by quantitative real-time RT-PCR for Cytokeratin 19 and were associated with liver metastases (p=0.00006). CK-19 declined in all responding patients and became elevated in 5/15 (30%) of progressing patients. All patients with HER-2-ECD >50 ng/ml had CK-19 cells detectable during therapy (p=0.008). Quantitative RT-PCR for HER2 in CTCs showed much lower sensitivity and specificity compared with CKl9, and was not found to be a useful measure in tracking disease.