Prognostic relevance of induced and spontaneous apoptosis of disseminated tumor cells in primary breast cancer patients.

Abstract

e21003 Background: An imbalance between cell proliferation and programmed cell death leads to tumor growth. Although most cytostatic agents used in systemic therapy of breast cancer induce an apoptosis in tumor cells leading to their destruction, a high ratio of apoptotic cells in primary breast cancer is correlated with poor prognosis. The purpose of this study was to investigate the incidence and prognostic significance of apoptotic disseminated tumor cells (DTC) in bone marrow (BM) of primary breast cancer (PBC) patients. Methods: PBC patients who underwent primary surgery (PS) or were treated with neoadjuvant chemotherapy (NACT) between 01/2003 and 12/2007 were included into this prospective study. BM aspirates were analyzed by immunocytochemistry (M30 antibody) using ACIS system (Chromavision) according to the ISHAGE evaluation criteria. Patients without DTC in the BM were excluded from the study. Survival data were evaluated after a median follow up of 44 months. Results: BM aspirates of 383 PBC patients were analyzed. DTC were M30 positive in 82 of 298 (27%) patients who underwent PS and 41 of 85 (48%) patients treated with NACT. After NACT, the incidence of apoptotic cells in patients with complete/partial remission as compared to patients with stable/progressive disease was 63%/53% vs. 31%/0% (p=0.034). In the NACT group, M30-positive patients suffered less likely of a relapse than those without apoptotic DTC (7% vs. 23% of the events, p = 0.049). Inversely, overall survival in the PS group was significantly shorter in M30-positive as compared to M30-negative patients (75 months, 95% CI: 68-81 months vs. 84 months, 95% CI: 81-86 months; p = 0.008). Conclusions: Apoptotic DTC can be detected in breast cancer patients before and after systemic treatment. The presence of apoptotic DTC in BM of breast cancer patients can reflect the effects of neoadjuvant treatment. Spontaneous and chemotherapy-induced apoptosis may have different prognostic implications.