MicroRNA-30c expression level is an independent predictor of clinical benefit of endocrine therapy in advanced estrogen receptor positive breast cancer.
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 P-values <0.01). In multivariate analysis, corrected for the traditional predictive factors, only hsa-miRNA-30c was an independent predictor (P-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.
Rodríguez-González
F Germán
FG
Department of Medical Oncology, Erasmus Medical Center Rotterdam, Josephine Nefkens Institute and Cancer Genomics Centre, Dr. Molewaterplein 50, Be 4.02 (lab)/4.35b (office), PO Box 2040, 3000 CA Rotterdam, The Netherlands. f.rodriguezgonzalez@erasmusmc.nl
Sieuwerts
Anieta M
AM
Smid
Marcel
M
Look
Maxime P
MP
Meijer-van Gelder
Marion E
ME
de Weerd
Vanja
V
Sleijfer
Stefan
S
Martens
John W M
JW
Foekens
John A
JA
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D011960:Receptors, Estrogen / Q000378:metabolism*; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D015398:Signal Transduction; D016019:Survival Analysis; D013629:Tamoxifen / Q000627:therapeutic use
D000970:Antineoplastic Agents; D035683:MicroRNAs; D011960:Receptors, Estrogen; D020845:Selective Estrogen Receptor Modulators; D013629:Tamoxifen