Assessing the efficacy of targeted therapy using circulating epithelial tumor cells (CETC): the example of SERM therapy monitoring as a unique tool to individualize therapy.

摘要

PURPOSE: In malignant tumors, predictive markers have been developed with respect to targeted therapies. One of the first targeted therapies was the hormone-blocking treatment of tumors of the male and female reproductive system. A typical therapy in breast cancer is the use of the selective estrogen receptor modulator, tamoxifen. However, only some of the patients, positive for the target molecules, respond to the selected therapy. It would, therefore, be highly desirable to have a tool to promptly assess the therapeutic efficacy of the applied agent in the individual patient. METHODS: Longitudinal observation of CETC provides a unique tool for monitoring therapy response. About 178 patients with breast cancer were followed prospectively during hormone therapy, requiring only 1 ml of peripheral blood, using a fluorochrome-labeled antibody against surface-epithelial antigen. Image analysis allowed CETC numbers to be calculated in relation to blood volume and monitoring over the entire course of treatment. RESULTS: A more than tenfold increase in CETC during therapy was a strong indicator of looming relapse (P = 0.0001 hazard ratio 5.5; 95% confidence interval 1,297-23,626), and a Cox regression analysis of age, tumor size, receptor expression, nodal status and previous treatment resulted in a regression model, in which CETC behavior was the parameter with the highest independent correlation to relapse-free survival. CONCLUSIONS: The change in the number of CETC (increase or decrease) may, in the future, be used to guide therapy in order to change to other available treatment options in good time.