Invited Speaker

Improving Personalized Cancer Care: Gauging the Response of Circulating Epithelial Tumor Cells (CETC) and Tumour Stem Cell Subpopulations to Guide Therapy in the Individual Patient
Katharina Pachmann
Germany

Background: Cells released from the primary tumor persisting and recirculating in the host can lead to the formation of distant metastases. We can show that CETC are detectable and can be quantified in the peripheral blood of almost all cancer patients including early-stage solid malignancies, although it was claimed that such cells are detectable only in a minor fraction of early-stage cancer patients.

Material and Methods: Using anticoagulated peripheral blood and red blood cell lysis as the only enrichment step, one centrifugation step, staining live cells with fluorochrome labelled anti-epithelial antigen as a search antibody, automated image analysis for detection of positive events and evaluation of exclusively surface located epithelial antigen on vital unfixed cells, CETC were detected in most patients with early stage cancer. Subsequently cells could be stained with anti-ALDH-antibody and in situ hybridized for HER2/neu amplification and quantified repeatedly during neo/adjuvant chemotherapy and during maintenance therapy with hormones or trastuzumab.

Results: 497 breast cancer patients were analyzed more than three times during the course of disease, 248 during neoadjuvant/adjuvant chemotherapy, 249 during trastuzumab and/or hormone therapy. Different pattern of therapy response were obtained with rapidly responding CETC changes over several logs in response to chemotherapy and slow and long-lasting changes extending over several years in response to hormone therapy and trastuzumab. Stem cell like staining was seen in a minor fraction of cells (1%) in about 10% of patients. An increase in cell numbers and in the fraction of HER2/neu amplified cells was under all treatment conditions unequivocally significantly correlated to highly increased risk of relapse.

Conclusions: CETC and subpopulation monitoring provides an invaluable tool for prompt gauging of systemic therapy in early stage solid tumors as a tool for therapy guidance and optimal personalized therapies to improve therapy results and spare unnecessary treatments.