title: Prognostic relevance of induced and spontaneous apoptosis of disseminated tumor cells in primary breast cancer patients.
abstract: BACKGROUND
  An imbalance between cell proliferation and programmed cell death can result in tumor growth. Although most systemic cytotoxic agents induce apoptosis in tumor cells, a high apoptotic rate in primary breast cancer correlates with poor prognosis. The aim of this study was to investigate the incidence and the prognostic significance of apoptotic disseminated tumor cells (DTC) in the bone marrow (BM) of breast cancer patients who either underwent primary surgery or primary systemic chemotherapy (PST).
  
  
  METHODS
  A total of 383 primary breast cancer patients with viable DTC in the BM were included into this study. Eighty-five patients were initially treated with primary systemic chemotherapy whereas 298 patients underwent surgery first. Detection of apoptotic DTC were performed by immunocytochemistry using the M30 antibody which detects a neo-epitope expressed after caspase cleavage of cytokeratin 18 during early apoptosis. The median follow up was 44 months (range 10-88 months).
  
  
  RESULTS
  Eighty-two of 298 (27%) primary operated patients and 41 of 85 (48%) patients treated with primary systemic systemic therapy had additional apoptotic DTC (M30 positive). In the neoadjuvant group M30-positive patients were less likely to suffer relapse than those without apoptotic DTC (7% vs. 23% of the events, p=0.049). In contrast, the detection of apoptotic DTC in patients treated by primary surgery was significantly associated with poor overall survival (5% vs. 12% of the events, p=0.008).
  
  
  CONCLUSIONS
  Apoptotic DTC can be detected in breast cancer patients before and after systemic treatment. The presence of apoptotic DTC in patients with PST may be induced by the cytotoxic agents. Thus, both spontaneous and chemotherapy-induced apoptosis may have different prognostic significance.
authors.forename: Natalia
authors.initials: N
authors.lastname: Krawczyk
authors.forename: Andreas
authors.initials: A
authors.lastname: Hartkopf
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Banys
authors.forename: Franziska
authors.initials: F
authors.lastname: Meier-Stiegen
authors.forename: Annette
authors.initials: A
authors.lastname: Staebler
authors.forename: Markus
authors.initials: M
authors.lastname: Wallwiener
authors.forename: Carmen
authors.initials: C
authors.lastname: Röhm
authors.forename: Juergen
authors.initials: J
authors.lastname: Hoffmann
authors.forename: Markus
authors.initials: M
authors.lastname: Hahn
authors.affiliation: Department of Obstetrics and Gynecology, University of Duesseldorf, Moorenstr, 5, 40225 Duesseldorf, Germany. tanja.fehm@googlemail.com.
authors.forename: Tanja
authors.initials: T
authors.lastname: Fehm
mesh_terms: D017209:Apoptosis / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D049109:Cell Proliferation; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D061986:MCF-7 Cells; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating; D011379:Prognosis