Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display

1654 - The clonal evolution of a breast tumor during neoadjuvant chemotherapy and metastasis

Date

10 Oct 2016

Session

Poster display

Presenters

Nicolai Litviakov

Citation

Annals of Oncology (2016) 27 (6): 68-99. 10.1093/annonc/mdw365

Authors

N.V. Litviakov1, N. Cherdyntseva2, M. Tsyganov3, M.K. Ibragimova4, A.V. Doroshenko5, P. Kazantseva5, J. Kzhyshkowska6, E. Slonimskaya5

Author affiliations

  • 1 Laboratory Of Oncovirology, Tomsk Cancer Research Institute, 634050 - Tomsk/RU
  • 2 Laboratory Of Molecular Oncology And Immunology, Tomsk Cancer Research Institute, 634009 - Tomsk/RU
  • 3 Laboratory Of Cell And Molecular Biomedicine, National Research Tomsk State University, Tomsk/RU
  • 4 Laboratory Of Oncovirology, Tomsk Cancer Research Institute, Tomsk/RU
  • 5 Department Of General Oncology, Tomsk Cancer Research Institute, Tomsk/RU
  • 6 Department Of Innate Immunity And Tolerance, University of Heidelberg, Heidelberg/DE
More

Resources

Abstract 1654

Background

In the present study we have examined the cytogenetic landscape (CNV – Copy Number Variation) of breast cancer prior to and following neoadjuvant therapy (NAC) and the associated tumor landscape alteration with chemotherapy efficiency as well as metastasis-free survival.

Methods

Breast cancer patients (n = 30) with stage IIA to IIIB received four cycles of systemic anthracycline-based NAC. To study CNVs in pre- and post-NAC tumor tissues microarray analysis was performed using the Affymetrix (USA) CytoScan HD Array.

Results

The obtained data indicate a direct correlation between CNV frequency alteration during NAC and tumor response to therapy (R = 0.71, p = 0.000011). We showed that the number of cytobands bearing mosaic CNV was decreased after chemotherapy in 43% patients (13/30). The analysis of all CNV, including amplifications and deletions demonstrated that NAC do not influence CNV frequency in 27% of patients (8/30). For 30% (9/30) of patients the appearance of new CNV was detected after chemotherapy. The origin of new clones with amplifications was revealed in 6 cases of 9. The new clones with amplifications in such loci as 5p, 6p, 7q, 8q, 9p, 10p, 10q22.1, 13q, 16p, 19p were detected. All these patients demonstrated distant metastasis where in 5 cases metastases were manifested within 2 years of follow up, excluding 1 patient surviving more than 4 years without metastases. All other patients (n = 24) who have not acquired the new tumor clones with Gain function after NAC did not manifest distant metastasis in 5-year follow-up (Kaplan-Meier, p = 0.00000 Log-rank test). In accordance with these findings amplified tumor clones (loci 5p, 6p, 7q, 8q, 9p, 10p, 10q22.1, 13q, 16p, 19p) could be considered as potential metastatic clones (named as seeds) which are able to go out from primary tumor sites in blood vessels with subsequent penetration to distant metastatic sites and in the case that prometastatic conditions exist in the microevironment they are able to give rise to metastases.

Conclusions

Our study results demonstrate that the clonal evolution of tumors under the exposure to NAC can stimulate tumor metastatic potential. Data obtained dictate a very intelligent approach to treatment with NAC to avoid metastasis stimulation.

Clinical trial identification

Legal entity responsible for the study

Tomsk Cancer Research Institute

Funding

Russian Foundation for Basic Research (project 15-04-03091)and Tomsk State University Competitiveness Improvement Program

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings