Circulating Epithelial Cells as a Tool for Monitoring Treatment Success of Primary Chemotherapy with Simultaneous or Sequential and without Trastuzumab.

Abstract

Abstract In spite of ample prognostic markers available in breast cancer, still a considerable proportion of patients with good prognostic markers suffers relapse whereas patients with poor prognostic markers may remain disease free. It would, therefore, be desirable to control, at the individual patient level, whether the applied therapy is effective. Our previous work indicates, that in cancer patients most of the epithelial cells circulating in peripheral blood (CETC) are part of the tumor and that the response of these cells reflects the response of the tumor to the applied therapies.Therefore monitoring the decrease or increase in numbers of these cells providing a unique tool for therapy surveillance was used to monitor neoadjuvant chemotherapy in 26 her2/neu positive breast cancer patients with either IHC3+ or FISH confirmed Her2/neu positive breast cancer. Patients were prospectively analysed for the number of CETC before therapy, before each new cycle of chemotherapy and during maintenance therapy at each visit initially every three months and subsequently at more extended intervals. 1ml of blood was drawn into EDTA vials, red blood cells lysed and the white blood cell pellet stained with FITC-labelled anti-Epcam. Green fluorescent cells were detected by image analysis and dead cells excluded due to red PI fluorescence.After an initial variable reduction of CETC during neoadjuvant chemotherapy, tightly connected to tumor reduction we regularly observed a massive release of cells from the shrinking tumor. Although these cells may not be able to settle in tumors with low metastatic potential, in 4/4 patients with Her2/neu positive tumors who did not receive trastuzumab the number of CETCs further increased after termination of therapy and surgery followed by rapid distant relapse indicating that the cells released in these patients may be highly aggressive with a high potential to settle and grow into metastases.It is, however not clear, whether sequential or simultaneous addition of trastuzumab to chemotherapy is preferential. In our hands 65% of the patients receiving simultaneous trastuzumab showed increasing CETCs and all have suffered relapse whereas all patients with decreasing CETCs are still in complete remission indicating that in the neoadjuvant situation during maintenance therapy an increase in CETC is the earliest indicator of imminent relapse.6/6 patients who received trastuzumab sequentially to the neoadjuvant treatment all showed decreasing numbers with all of them still without signs of disease after 4 years of follow up. Thus, trastuzumab was highly effective in this treatment and even if the tumor cells were not eliminated immediately, trastuzumab contributed to prevent them from settling and growing into metastases and CETC monitoring favours sequential trastuzumab. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3016.