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

Abstract

PurposeIn 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.MethodsLongitudinal 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.ResultsA 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.ConclusionsThe 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.

Phase I Dose Escalation Study with the Lewis Y Carbohydrate Specific Humanized Antibody IGN311

“…This is in accordance with Tanaka et al [43] who showed that in lung cancer patients, CTC counts significantly increased along with tumor progression, especially with development of distant metastasis. For breast cancer, Pachmann et al [44] showed that an increase of circulating epithelial tumor cells was a strong indicator for a relapse. In summary, the isolation and characterization of individual tumor cells from the blood of patients known to have metastatic cancer hold tremendous potential for new biological insight with very real clinical applications [45].…”

Clinical utility of a circulating tumor cell assay in Merkel cell carcinoma

“…CTCs have been proven to be useful prognostic markers in several carcinomas in which they correlate to disease progression and predict relapse 14,15 . In MCC, the presence of CTCs has been previously reported in 4 patients, typically as a single case 16,17,18 .…”

Behavior of circulating epithelial tumor cells (CETC) and FISH (fluorescence <i>in situ</i> hybridisation) of epidermal growth factor receptor (EGFR)-gene amplification in lung cancer patients during the course of therapy

“…Values were displayed in scattergrams and histograms. Both approaches enable the user to locate cells contained within the desired population for visual examination and to take fluoromicrographs [24].…”