PMID- 15887027
OWN - NLM
STAT- MEDLINE
DCOM- 20051101
LR  - 20181113
IS  - 0171-5216 (Print)
IS  - 0171-5216 (Linking)
VI  - 131
IP  - 8
DP  - 2005 Aug
TI  - Isolated tumor cells in the bone marrow (ITC-BM) of breast cancer patients before 
      and after anthracyclin based therapy: influenced by the HER2- and Topoisomerase 
      IIalpha-status of the primary tumor?
PG  - 539-46
AB  - PURPOSE: The presence of isolated tumor cells in the bone marrow (ITC-BM) is an 
      independent prognostic factor in all stages of breast cancer. Both the 
      expression/amplification of human epithelial growth factor receptor 2 (HER2) and 
      Topoisomerase IIalpha (TOP IIa), a key enzyme of DNA replication and main target 
      of anthracyclins, in breast cancer tissue seem to have predictive value regarding 
      the effectiveness of systemic therapies. METHODS: To investigate the correlation 
      between these factors and their influence on clinical outcome, tumor tissue of 54 
      patients who were screened for ITC-BM before and after anthracyclin-based 
      chemotherapy (abCTX) was examined for HER2 and TOP IIa by immunohistochemistry 
      (IHC) and fluorescence in situ hybridization (FISH). RESULTS: By IHC, 31% of the 
      tumors showed positive for HER2 (2+/3+), 14.6% were amplified in FISH. TOP IIa 
      expression (>50%) was found in 13/53 patients (25%), FISH was positive in 5/47 
      cases (11%). TOP IIa amplification was not seen in cases without HER2 
      amplification, five of the seven HER2 amplified cases also were amplified for TOP 
      IIa (71% co-amplification). Forty-three patients had adjuvant, seven 
      neo-adjuvant, four palliative abCTX. ITC-BM were present in 24% of patients 
      before and 31% after CTX. Patients with HER2 (IHC, P = 0.29) and TOP IIa (FISH, P 
      = 0.16) positive tumors tended to stay or become negative in BM status after 
      abCTX and vice versa. After a median follow-up of 44 months (6-127), none of the 
      factors reached significance for overall survival. Yet, patients with HER2 (P = 
      0.16) and TOP IIa (P = 0.09) positive tumors showed a trend towards prolonged 
      disease-free survival. Remarkably, none of the TOP IIa FISH-positive patients 
      developed distant metastases (P = 0.099) or died (P = 0.19) after CTX so far. 
      CONCLUSIONS: HER2- and TOP IIa positivity seem to improve the effect of abCTX. 
      The combination of the prognostic value of ITC-BM and the predictive capacity of 
      HER2 and TOP IIa could help to stratify patients for certain therapies. The 
      direct examination of those factors on ITC-BM is the focus of ongoing studies.
FAU - Schindlbeck, C
AU  - Schindlbeck C
AD  - I. Frauenklinik, Klinikum der Ludwig-Maximilians-Universitat, Maistrasse 11, 
      80337 Munich, Germany. Christian.Schindlbeck@med.uni-muenchen.de
FAU - Janni, W
AU  - Janni W
FAU - Shabani, N
AU  - Shabani N
FAU - Kornmeier, A
AU  - Kornmeier A
FAU - Rack, B
AU  - Rack B
FAU - Rjosk, D
AU  - Rjosk D
FAU - Gerber, B
AU  - Gerber B
FAU - Braun, S
AU  - Braun S
FAU - Sommer, H
AU  - Sommer H
FAU - Friese, K
AU  - Friese K
LA  - eng
PT  - Journal Article
DEP - 20050511
PL  - Germany
TA  - J Cancer Res Clin Oncol
JT  - Journal of cancer research and clinical oncology
JID - 7902060
RN  - 0 (Anthracyclines)
RN  - 0 (Antibiotics, Antineoplastic)
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (DNA-Binding Proteins)
RN  - EC 2.7.10.1 (Receptor, ErbB-2)
RN  - EC 5.99.1.3 (DNA Topoisomerases, Type II)
SB  - IM
MH  - Anthracyclines/*therapeutic use
MH  - Antibiotics, Antineoplastic/*therapeutic use
MH  - Antigens, Neoplasm/*analysis
MH  - Biomarkers, Tumor/*analysis
MH  - Bone Marrow/*pathology
MH  - Bone Marrow Neoplasms/pathology
MH  - Breast Neoplasms/*chemistry/*drug therapy/pathology
MH  - DNA Topoisomerases, Type II/*analysis
MH  - DNA-Binding Proteins/*analysis
MH  - Female
MH  - Humans
MH  - Immunohistochemistry
MH  - In Situ Hybridization, Fluorescence
MH  - Predictive Value of Tests
MH  - Prognosis
MH  - Receptor, ErbB-2/*analysis
MH  - Risk Factors
EDAT- 2005/05/12 09:00
MHDA- 2005/11/03 09:00
CRDT- 2005/05/12 09:00
PHST- 2004/11/22 00:00 [received]
PHST- 2005/02/14 00:00 [accepted]
PHST- 2005/05/12 09:00 [pubmed]
PHST- 2005/11/03 09:00 [medline]
PHST- 2005/05/12 09:00 [entrez]
AID - 10.1007/s00432-005-0683-y [doi]
PST - ppublish
SO  - J Cancer Res Clin Oncol. 2005 Aug;131(8):539-46. doi: 10.1007/s00432-005-0683-y. 
      Epub 2005 May 11.