These results show that peripherally circulating tumor cells are influenced by systemic chemotherapy and that an increase (even after initial response to therapy) of 10-fold or more at the end of therapy is a strong predictor of relapse and a surrogate marker for the aggressiveness of the tumor cells.

Background: Having demonstrated in a previous report that the response of circulating epithelial tumor cells (CETC) during the first cycles of primary (neoadjuvant) chemotherapy perfectly reflects the response of the tumor, in the present study the changes in cell numbers during subsequent cycles and their possible impact on the therapy's outcome were examined. Patients and methods:In 58 breast cancer patients CETC were quantified during therapy with either EC (epirubicin/ cyclophosphamid) or dose intensified E (epirubicin) followed by taxane, with or without trastuzumab, and subsequent CMF (cyclophosphamid/methorexate/ fluorouracil).Results: CETC numbers declined more than 10-fold (good response) in 65% (her2/neu-negative) and 55% (her2/neu-positive) of patients during EC, and in 60% during dose intensified E, respectively, followed by an increase of CETC in all patients. CETC remained increased, decreasing only when adding CMF. A good initial response correlated with estrogen-receptor negativity, a poor response with early distant relapse (P < 0,0001, hazard ratio = 11.91). Conclusion:Response of CETC already during the first cycles of neoadjuvant treatment predicts the final response of the tumor. Hitherto unknown effects of the release of tumor cells during therapy further our understanding of tumor-blood interaction and may improve access of agents like antibodies to cells. The impact on the further course of disease remains to be evaluated.

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.

Although considerable progress has been achieved in breast cancer diagnosis and treatment, the live-saving effect of mammography has hardly been measurable and the benefit of taxanes regarded as highly active is still a matter of debate, possibly because treatment effects have hitherto been mainly determined from the solid part of the tumor, due to lack of measurability of the systemic part of the disease. Here, we have quantified the influence on the systemic disease, cells mobilized from the solid tumor. Increased numbers of circulating epithelial cells were observed in screened individuals and still higher numbers in breast cancer patients with repeated mammograms as compared to mammogram naïve individuals. Taxanes as part of the subsequent systemic treatment led to mobilization of tumor suspect cells in up to 78% cases and the majority of relapses have occurred in these patients. Surgery-induced activation of disseminated cells may additionally contribute to metastasis formation.

Background In breast cancers, the gene for the growth factor receptor HER2 can be ampliWed leading to increased aggressiveness and metastasis formation. The monoclonal antibody trastuzumab prolongs relapse-free survival highly signiWcantly but eventually many patients relapse. Method In this study, CETC were monitored using the Maintrac ® method during adjuvant trastuzumab treatment and during subsequent treatment with capecitabine/lapatinib.