Erschienen in:
01.08.2005 | Original Paper
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 IIα-status of the primary tumor?
verfasst von:
C. Schindlbeck, W. Janni, N. Shabani, A. Kornmeier, B. Rack, D. Rjosk, B. Gerber, S. Braun, H. Sommer, K. Friese
Erschienen in:
Journal of Cancer Research and Clinical Oncology
|
Ausgabe 8/2005
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Abstract
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 IIα (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.