ArticleJournal of cancer research and clinical oncology2005
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?
Article in Journal of cancer research and clinical oncology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 14 citations in OpenAlex.
- Topoisomerase II alpha and TLE3 as predictive markers of response to anthracycline and taxane-containing regimens for neoadjuvant chemotherapy in breast cancer.OncoTargets and therapy · 2014Article
- HER2 and TOP2A in high-risk early breast cancer patients treated with adjuvant epirubicin-based dose-dense sequential chemotherapy.Journal of translational medicine · 2012Article
- Topoisomerase II alpha gene copy loss has adverse prognostic significance in ERBB2-amplified breast cancer: a retrospective study of paraffin-embedded tumor specimens and medical charts.Journal of hematology & oncology · 2008Article
- Prognostic relevance of disseminated tumor cells in the bone marrow and biological factors of 265 primary breast carcinomas.Breast cancer research : BCR · 2005Article
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe 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.
methodsTo 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).
resultsBy 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.
conclusionsHER2- 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.
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