MicroRNA-30c expression level is an independent predictor of clinical benefit of endocrine therapy in advanced estrogen receptor positive breast cancer

F. Germán Rodríguez-González (1, 2, 3) , Anieta M. Sieuwerts (1) , Marcel Smid (1) , Maxime P. Look (1) , Marion E. Meijer-van Gelder (1) , Vanja Weerd (1) , Stefan Sleijfer (1) , John W. M. Martens (1) , John A. Foekens (1)

1 Erasmus MC - Erasmus University Medical Center [Rotterdam]
2 Canary Institute for Cancer Research (ICIC)
3 Department of Biochemistry and Physiology, Faculty of Health Sciences

MicroRNAs (miRNAs) are small RNA molecules that modulate gene expression and which have been implicated in cancer. We evaluated whether five candidate predictive miRNAs, derived from a pilot study in which 249 miRNAs were assayed, were associated with clinical benefit of tamoxifen therapy in advanced breast cancer. These five miRNAs were measured in an independent series of 246 estrogen receptor (ER)-positive primary breast tumors of patients who received tamoxifen for advanced disease by quantitative Real Time PCR. Univariate analysis showed that higher expression levels of hsa-miR-30a-3p, hsa-miR-30c, and hsa-miR-182 were significantly associated with benefit of tamoxifen treatment and with longer PFS (all -values <0.01). In multivariate analysis, corrected for the traditional predictive factors, only hsa-miRNA-30c was an independent predictor (-value <0.01). Finally, in an attempt to understand the biology connected to this miRNA, Global testing pathway analysis showed an association of hsa-miRNA-30c expression with HER and RAC1 signaling pathways. We identified hsa-miRNA-30c as an independent predictor for clinical benefit of tamoxifen therapy in patients with advanced breast cancer. Assessment of tumor levels and connected pathways could be helpful to improve treatment strategies.

Mots clés: Breast cancer; Tamoxifen; miRNAs

F. Germán Rodríguez-González, Anieta M. Sieuwerts, Marcel Smid, Maxime P. Look, Marion E. Meijer-van Gelder, et al.. MicroRNA-30c expression level is an independent predictor of clinical benefit of endocrine therapy in advanced estrogen receptor positive breast cancer. Breast Cancer Research and Treatment, 2010, 127 (1), pp.43-51. ⟨10.1007/s10549-010-0940-x⟩. ⟨hal-00594476⟩