Senologie - Zeitschrift für Mammadiagnostik und -therapie 2012; 9 - A7
DOI: 10.1055/s-0032-1313373

Prognostic significance of apoptotic disseminated tumor cells in primary breast cancer patients

M Banys 1, 2, A Hartkopf 1, N Krawczyk 1, S Becker 1, D Wallwiener 1, T Fehm 1
  • 1Universitäts-Frauenklinik Tübingen, Universität Tübingen, Tübingen
  • 2Frauenklinik, Marienkrankenhaus Hamburg, Hamburg

Background:

An imbalance between cell proliferation and programmed cell death leads to tumour growth. Although most cytostatic agents used in systemic therapy of breast cancer induce an apoptosis in tumour 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 (1) the incidence and (2) prognostic significance of apoptotic tumour cells in bone marrow (BM) of primary breast cancer patients who underwent primary surgery or were treated with neoadjuvant chemotherapy.

Methods:

261 primary breast cancer patients treated at the Department of Gynecology and Obstetrics (University Hospital Tuebingen, Germany) between 2003 and 2007 were included into our study. 186 underwent primary breast surgery and 75 were treated with neoadjuvant chemotherapy. BM aspirates were analysed by immunocytochemistry (M30 antibody) using ACIS system (Chromavision) according to the ISHAGE evaluation criteria. The survival data were evaluated after 25 months of follow up.

Results:

In 50 of 186 (27%) patients who underwent a primary surgery and 34 of 75 (45%) patients treated with neoadjuvant systemic therapy M30 positive disseminated tumour cells (DTC) could be detected. The incidence of apoptotic cells was significantly higher in patients with complete/partial remission compared to patients with stable/progressive disease (65% and 49% vs. 31% and 0%). In the group of neoadjuvant treated patients M30-positive BM status was correlated with an improved disease-free survival (9% relapsed vs. 22% in M30-negative group). Inversely, the detection of apoptotic DTC in patients with primary operated breast cancer was associated with poor prognosis (8/50 (16%) vs. 9/136 (7%) of the events).

Conclusion:

(1) Apoptotic DTC can be detected in breast cancer patients before and after the systemic treatment.

(2) The presence of apoptotic DTC in BM of breast cancer patients can reflect the effects of neoadjuvant treatment.

(3) Spontaneous and chemotherapy-induced apoptosis can possibly have different prognostic significance.