Circulating And Disseminated Tumor Cells After Neoadjuvant Therapy In Primary Breast Cancer

Background: Disseminated tumor cells (DTCs) have been identified in approximately 30% of patients with primary breast cancer (BC) and predict outcome. Tumor cells in the blood (CTCs) predict outcome in metastatic BC, but their significance in primary BC is unclear. Neoadjuvant chemotherapy (NACT) is effective in reducing primary tumors or eradicating lymph node metastases prior to surgery, but the effect of NACT on DTCs and CTCs is unknown. Methods: We measured CTCs and DTCs in 107 patients with operable BC. Blood and bone marrow samples were collected following NACT completion. DTCs were identified using anti-cytokeratin immunostaining. CTCs were detected using the Cell Search system. Primary tumor markers, lymph node status, types/response to NACT were compared to CTC and DTC presence. Results: Mean age at diagnosis was 51 years; median follow-up was 25 months. DTCs were identified in 27% and CTCs in 21% of patients following NACT. We found no associations between DTCs and primary tumor characteristics or lymph node status, however, ≥3 positive lymph nodes (intra-operatively) predicted CTCs (P=0.03). Conclusions: A significant number of primary BC patients have CTCs and DTCs following NACT, irrespective of primary tumor characteristics or response to NACT. Longer follow-up will determine if these cells predict outcome. Keywords—Circulating tumor cells, disseminated tumor cell, micrometastase, breast cancer