Circulating HER2/neu
Biomarkers in Breast Cancer(2006)
摘要
The HER2/neu oncogene and its p185 receptor protein is an indicator of a more aggressive form of breast cancer. The HER2/neu status guides
Herceptin® therapy, specifically directed to the extracellular domain (ECD) of the HER2/neu oncoprotein. The HER2/neu ECD
is shed from cancer cells into the circulation and is measurable by immunoassay. We performed an in-depth review of the peer-reviewed
literature on circulating ECD levels with respect to prevalence, prognosis, prediction of response to therapy, and monitoring
of breast cancer. Studies showed that the prevalence of an elevated ECD in patients with primary breast cancer varied between
0% and 38% (mean 18.5%) while in metastatic breast cancer the range was from 23% to 80% (mean 43%). Some women who have HER2/neu-negative
tumors by tissue testing develop elevated ECD levels in metastatic disease. Elevated ECD levels have been correlated with
indicators of poor prognosis, for example, overall survival and disease-free survival. Elevated ECD levels predict a poor
response to hormone therapy and some chemotherapy regimens but can predict improved response to combinations of Herceptin
and chemotherapy. Many studies support the value of monitoring ECD levels during breast cancer progression, as serial increases
precede the appearance of metastases using imaging techniques, and longitudinal ECD changes paralleled the clinical course
of disease. The monitoring of circulating HER2/neu ECD levels provides a tool for assessing prognosis, predicting the response
to therapy and for earlier detection of disease progression and intervention with appropriate therapy. Additional prospective
studies are required to validate these potential applications.
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