Abstract P4-07-08: The predictive and prognostic role of tumoral miRNA expression levels in patients with breast cancer (BC) treated with neoadjuvant chemotherapy (NAC)
Authors: Eralp Y , Keskin S , Gezer U , Tukenmez M , Muslumanoglu M , Dalay N , Disci R , Yavuz E , Igci A 
Published: August 2014

Over the last decade, miRNA's have gained considerable interest due to the accumulating evidence regarding their relevant regulatory functions on cancer initiation, proliferation and progression. Furthermore, there are data showing that miRNA's can have a predictive role in response to NAC. The aim of this study is to evaluate the association between miRNA expression profile and response to NAC in patients with BC. 21 patients who received NAC consisting of 4 cycles of antracycline and cyclophosphamide (EC), followed by 4 cycles of docetaxel (T) were included in this study. Tumor core biopsies and blood specimens were collected before initiation, before the 5th cycle and after the completion of NAC for pathologic evaluation, miRNA expression and circulating correlative miRNA levels. The miRNA profile consisted of 9 miRNA's that were previously shown to be related to anthracycline and taxane resistance, as well as those associated with various intracellular functions. Associations with miRNA expression and clinical and pathologic variables, including response were evaluated by the Spearmann Correlation test. Response assessment was carried out every couple of cycles by physical examination, and radiologic evaluation after 4 and 8 cycles, respectively. Clinical response to EC was complete regression in 4.76% (n:1), PR in 66.7% (n:14), minimal response in 23.8% (n:5); and progression in 4.76% (n:1); all patients responded to docetaxel with 1 having CR and 20 PR. Pathologic response evaluation revealed CR in 7 patients (33.3%), good PR (defined as more than 50% regression in the viable tumor cells) in 8 (38.1%) and minimal PR in 6 (28.6%). Baseline levels of miRNA expression before initiation of NAC from the lowest to the highest level were as follows: miR10b (mean relative value (MRV): 0.24), miR-200c, miR34a, miR-11, let7a, miR-200c, miR-21, miR-195 and miR-221 (MRV: 132.5). Although each miRNA tested were in positive correlation with each other (p&lt;0.05), there was no association with any miRNA with known clinic-pathologic variables, such as ER, PR, Her-2/neu or Ki67 levels. All miRNA's showed higher levels in patients presenting with stage 2 disease compared to those with stage 3 disease, which was marginally significant for miR-155 and miR-21 (p:0.05). After 4 cycles of EC miR-21 and miR-195 expression decreased significantly (mean decrease 500 times the initial level) (p&lt;0.05), which was more evident in patients with earlier stage at presentation (stage 2 versus stage 3 disease (p:0.03)). There were no significant correlations seen with any miRNA and response to taxane-based NAC, since all patients showed a response. Furthermore, there was no correlation between pCR and the miRNA's tested. Nevertheless, there was a trend for higher pre-treatment miR-34 levels predictive for a good clinical response to EC, which was defined as more than 50% regression in the largest tumor diameter (p:0.07). In this preliminary study, we have shown that a substantial decrease in miR-155, -21,and -195 expressions after 4 cycles of EC may be associated with clinical response to anthracycline-based NAC. Furthermore, a higher miR-34 expression may predict for athracycline responsiveness.

Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-07-08.