41P - Mir-223 overexpression is associated with increased expression of EGFR and worse prognosis in Indonesian TNBC patients

Background

Triple-negative breast cancer (TNBC) is associated with more aggressive disease and worse survival compared to other breast cancer subtypes. We aim to analyze the role of oncogenic mir-223 as a possible negative driving factor in TNBC through its prognostic value and association with unfavorable clinicopathologic characteristic.

Methods

We retrospectively analyzed the association of pre-treatment mir-223 expression with clinicopathologic characteristics and 3-years overall survival (OS) of Indonesian TNBC patients treated in a tertiary center during 2014-2017. Cytokeratin5/6 (CK5/6) and Epidermal Growth Factor Receptor (EGFR) expressions were examined using immunohistochemistry by 2 independent blinded pathologists. Mir-223 level of tumor tissue was measured using Real-Time qRT-PCR. Cutoff value for mir-223 was determined using Receiver Operating Curve (ROC). Chi-square and Fisher’s exact tests were used to analyze the association between categorical variables, while Kaplan-Meier curve was used to perform survival analysis.

Results

Fifty-three stage I-IV TNBC patients were included in the analysis. The mean age of our patients was 51.3 years old. Early stage, locally advanced stage, and metastatic disease respectively were found in 7 (13.2%), 38 (71.7%), and 8 (15.1%) patients. The optimal cutoff value for mir-223 was 23.435 (AUC: 0.706, 95%CI: 0.565-0.848; p: 0.01; Sensitivity: 78.6%; Specificity: 56%) and was used to classify mir-223 expression into over- and under-expressed groups. Mir-223 overexpression was associated with increased expression of EGFR (69.7% vs. 35%, p: 0.022) and lower 3-years OS (33.3% vs. 70%; mean OS±SE (months): 25.66±1.58 vs. 30.23±1.99; p log rank: 0.029). No significant association was observed between mir-223 expression with other clinicopathologic characteristics (age, BMI, stage, tumor size, nodal status, distant metastasis, and CK5/6 expression).

Conclusions

Pre-treatment mir-223 level of expression in Indonesian TNBC patients is correlated with poor survival through increase of EGFR expression. Thus, targeting mir-223 becomes a potential therapeutic strategy for TNBC patients. However, further study is needed to validate this result.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.