Breast cancer is the most common malignancy that develops in women, responsible for the highest cancer-related death rates worldwide. Triple negative breast cancer represents a clinically important breast cancer subtype that has an aggressive clinical phenotype, is associated with a higher likelihood of metastasis and that is not responsive to current targeted therapies. miRNAs have emerged as an attractive candidate for biomarkers and treatment targets in breast cancer and our studies indicate that they show a general down-regulated in lymph node positive breast cancers and in matched lymph node metastases in the triple negative subtype. In addition, reduced expression of the enzyme responsible for miRNA production, Dicer, has been associated with shorter metastasis-free survival in breast cancer and with the triple negative subtype. However, the role of Dicer and Drosha (another enzyme involved in miRNA biogenesis), in the progression of triple negative breast cancer is not known.
The aim of this study was to investigate if Dicer and Drosha expression was altered in the progression of triple negative breast cancer from normal to primary breast cancer to lymph node metastases. For this analysis, we have examined the mRNA expression of Dicer and Drosha by real-time PCR in 34 grade 3 primary triple negative breast cancers (with known lymph node status) and in 13 matched lymph node metastases compared with 18 matched normal breast tissues. The relationship of their expression with age at diagnosis, tumour size and number of positive lymph nodes will be presented. This study will provide novel insight into the regulation of Dicer and Drosha in the progression of triple negative breast cancer.