Affiliations: Department of Experimental Oncology, Institute for
Oncology and Radiology of Serbia, Belgrade, Serbia | Department of Clinical Oncology, Institute for
Oncology and Radiology of Serbia, Belgrade, Sebia
Note: [] Corresponding author: Nataša Todorović-Raković,
Department of Experimental Oncology, Institute for Oncology and Radiology of
Serbia, Pasterova 14, 11000 Belgrade, Serbia. Tel.: +381 11 20 67 213; Fax: +381 11 2685 300; E-mail: todorovicn@ncrc.ac.yu
Abstract: The aim of this study was to determine the relationship between
amplification of HER2 (Human epidermal growth factor receptor 2) and Topo2a
(topoisomerase 2a) and their influence on prognosis in metastatic breast cancer
(MBC) patients. Amplification of both HER2 and Topo2a genes was determined by
chromogenic in situ hybridization (CISH) in primary tumor tissue of 71 MBC
patients. Starting point for follow-up was the time of diagnosis of metastatic
disease. Although there was significant correlation between HER2 amplification
and Topo2a alterations, Topo2a amplification was not strictly related to HER2
amplification. Follow-up of patients showed that there was no difference in MBC
survival between HER2-nonamplified and HER2-amplified patients for subgroup as
whole, but there was significant difference in MBC survival between patients
with and without Topo2a amplification. HER2 amplification showed prognostic
value in subgroups of patients, as well as Topo2a. Combination of these two
genes with different status (nonamplified, amplified, coamplified) indicated
that they might have additive effect. Also, it has been shown that
Topo2a-amplified cases have poorer survival than Topo2a-nonamplified, when
treated with CMF therapy. Topo2a amplification seems to be more promising
biomarker of MBC survival, than HER2, and potential marker of resistance to CMF
therapy.
Keywords: Metastatic breast cancer, CISH, HER2, Topo2a
