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Gene profiling and circulating tumor cells as biomarker to prognostic of patients with locoregional breast cancer

Abstract

The gene profile of primary tumors, as well as the identification of circulating tumor cells (CTCs), can provide important prognostic and predictive information. In this study, our objective was to perform tumor gene profiling (TGP) in combination with CTC characterization in women with nonmetastatic breast cancer. Biological samples (from peripheral blood and tumors) from 167 patients diagnosed with stage I, II, and III mammary carcinoma, who were also referred for adjuvant/neoadjuvant chemotherapy, were assessed for the following parameters: (a) the presence of CTCs identified by the expression of CK-19 and c-erbB-2 in the peripheral blood mononuclear cell (PBMC) fraction by quantitative reverse transcription PCR (RT-PCR) and (b) the TGP, which was determined by analyzing the expression of 21 genes in paraffin-embedded tissue samples by quantitative multiplex RT-PCR with the Plexor® system. We observed a statistically significant correlation between the progression-free interval (PFI) and the clinical stage (p = 0.000701), the TGP score (p = 0.006538), and the presence of hormone receptors in the tumor (p = 0.0432). We observed no correlation between the PFI and the presence or absence of CK-19 or HER2 expression in the PBMC fraction prior to the start of treatment or in the two following readouts. Multivariate analysis revealed that only the TGP score significantly correlated with the PFI (p = 0.029247). The TGP is an important prognostic variable for patients with locoregional breast cancer. The presence of CTCs adds no prognostic value to the information already provided by the TGP.

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Acknowledgments

We thank Fundação de Amparo a Pesquisa do Estado de São Paulo (Fapesp) for supporting this research (Proc. no. 09/50361-4).

Conflicts of interest

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Author contributions

RKK, FSG, and BCAA carried out the validation of genes and Plexor system. VVB, AEC, and FLAF carried out the lab analysis from blood samples. NS and JN contributed to the acquisition of data. BCAA and FLAF contributed to the analysis and interpretation of data. ADG performed the statistical analysis. ADG conceived the study and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.

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Correspondence to Auro Del Giglio.

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Kuniyoshi, R.K., de Sousa Gehrke, F., Alves, B.C.A. et al. Gene profiling and circulating tumor cells as biomarker to prognostic of patients with locoregional breast cancer. Tumor Biol. 36, 8075–8083 (2015). https://doi.org/10.1007/s13277-015-3529-5

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  • DOI: https://doi.org/10.1007/s13277-015-3529-5

Keywords

  • Breast neoplasms
  • Keratin-19
  • Cancer chemotherapy drugs
  • Multiplex polymerase chain reaction
  • Biological markers
  • Transcriptome