Apoptotic disseminated tumor cells reflect response to primary chemotherapy in breast cancer

Abstract

654 Background: Primary chemotherapy (pCHT) is an established method to reduce tumor size (downstaging) in breast cancer patients before performing breast conserving therapy. The consequences of pCHT on tumor cell dissemination in these patients are not known. The aim of this study was to investigate (1) the incidence of disseminated tumor cells (DTC) including apoptotic DTC in patients with breast cancer after primary chemotherapy and (2) its correlation with pathological therapy response. Methods: Bone marrow aspiration was performed in 157 patients after primary chemotherapy. Cytokeratin-positive cells were detected by immunocytochemistry using the AB45-B/B3 anti-cytokeratin antibody. For detection of apoptotic tumor cells the antibody M30 (Roche Diagnostics, Germany) was used. M30 reacts with a neo-epitope expressed only after caspase cleavage of CK 18 during early apoptosis. Results: The incidence of disseminated tumor cells in breast cancer patients was 57% (84 of 157 pts) after completion of primary systemic therapy. Tumor dissemination was observed more frequently in patients with no change/progressive disease (NC+PD: 63%) than in those who showed partial (PR) or complete remission (CR) of the primary tumor (PR+CR: 43%) (p<0.05). However, 9 of 23 (40%) patients with complete response were still bone marrow positive. Apoptotic tumor cells were present in 36 of 157 (23%) breast cancer patients. The positivity rate of apoptotic cells was higher in bone marrow positive patients with PR or CR (42%) compared to those with stable disease (SD) (26%). No apoptotic tumor cells were detected in patients with tumor progression (n=5). Conclusions: The pathological therapy response is reflected by the presence of apoptotic tumor cells in the bone marrow of breast cancer patients. However, patients with complete response may still have non apoptotic disseminated tumor cells. Patients with tumor cell dissemination after primary systemic therapy may be benefit from additional secondary adjuvant treatment (e.g. bisphosphonates, antibody based strategies). No significant financial relationships to disclose.