64P - Neoadjuvant chemotherapy in breast cancer patients induces miR-34a expression

Date 07 May 2015
Event IMPAKT 2015
Session Welcome reception and Poster Walk
Topics Anti-Cancer Agents & Biologic Therapy
Breast Cancer
Translational Research
Presenter Pierre Freres
Citation Annals of Oncology (2015) 26 (suppl_3): 15-24. 10.1093/annonc/mdv117
Authors P. Freres1, C. Josse2, N. Bovy3, M. Boukerroucha2, I. Struman3, V. Bours2, G. Jerusalem1
  • 1Medical Oncology, University of Liege, CHU Sart Tilman, 4000 - Liège/BE
  • 2Human Genetic, University of Liege, CHU Sart Tilman, 4000 - Liège/BE
  • 3Laboratory Of Molecular Angiogenesis, University of Liege, CHU Sart Tilman, 4000 - Liège/BE



Introduction: Circulating microRNAs (miRNAs) have been extensively studied in cancer as biomarkers but little is known regarding the influence of anti-cancer drugs on their expression levels. In this article, we describe the modifications of circulating miRNAs profile after neoadjuvant chemotherapy (NAC) for breast cancer.

Methods: The expression of 188 circulating miRNAs was assessed in the plasma of 25 patients before and after NAC by RT-qPCR. miR-34a, that was significantly increased after NAC, was measured in plasma of 45 NAC-treated breast cancer patients. Futhermore, miR-34a expression level was assessed by qRT-PCR and in situ hybridization in tumor tissue before and after chemotherapy in 7 patients with pathological partial response (pPR) to NAC. This chemotherapy-induced miRNA was further studied in the plasma of 22 patients with adjuvant chemotherapy (AC) as well as in 12 patients who did not receive any chemotherapy.

Results: Twenty-five plasma miRNAs were modified by NAC. Among these miRNAs, tumor suppressor miR-34a was highly upregulated, notably in pPR patients with HER2-positive and triple negative breast cancers. miR-34a level was also elevated in the remaining tumor tissue after NAC treatment. Comparisons of the plasma miRNA profiles after NAC and AC suggested that chemotherapy-induced miRNAs originated from both tumoral and non-tumoral compartments. Studying the kinetics of circulating miR-34a expression during NAC revealed that its level was especially increased after anthracycline-based chemotherapy. Futhermore, circulating miR-34a upregulation was correlated with high sensitive-troponins T increase after anthracyclines.

Conclusion: This study is the first to demonstrate that NAC specifically induces miR-34a expression in plasma and tumor tissue, which might be involved in the anti-tumor effect and the cardiotoxicity of chemotherapy in breast cancer patients.

Disclosure: All authors have declared no conflicts of interest.