49P - Circulating miRNA signatures to predict recurrence in patients with pathological complete response of triple-negative breast cancer

Background

Triple-negative breast cancer (TNBC) is characterized by aggressive clinicopathological features and is associated with a poor prognosis. Identifying patients who respond to chemotherapy and yet relapse early remains the subject of many studies and a critical goal for effective personalized therapies. In the present study, we investigated the role of miRNAs in TNBC that responded to neoadjuvant chemotherapy (NAC). Circulating miRNAs were isolated from TNBC patients who underwent NAC and who had a pathologic complete response (pCR).

Methods

The miRNA expression analysis was conducted by nCounter® Human v3 miRNA assay (NanoString Technologies, Seattle, USA) on plasma samples. Sample collected from patients participating in a phase II prospective clinical trial. About 800 human miRNAs were screened, and the resulting data were normalized using the normalization method based on the low coefficient of variation (low CV). Further analysis was carried out using parameters such as fold change and area under the curve (AUC).

Results

A total of 33 differentially expressed miRNAs were identified between relapsed and non-relapsed patients who achieved pCR. Of the 33 miRNAs, only one was downregulated. Of these, we identified 7 miRNAs (hsa-miR-654-5p, hsa-miR-433-5p, hsa-miR-520c-3p, hsa-miR-376a-2-5p, has-miR-4741, has-miR- 513c-3p, hsa-miR-506-5p) which showed better accuracy to discriminate patients with pCR with a higher probability of relapse, with the area under the curve value ranging from 0.80 to 0.93. In network analysis, "TGF-beta signaling pathway", "cancer transcriptional dysregulation" and "JAK-STAT signaling pathway" were identified as the crucial pathways in breast cancer patients who also developed recurrence.

Conclusions

In conclusion, our study hypothesizes that circulating miRNAs may be useful non-invasive biomarkers to identify patients who are more likely to develop recurrence even after achieving pCR in TNBC patients.

Clinical trial identification

NACATRINE trial (NCT02978495).

Editorial acknowledgement

Legal entity responsible for the study

Barretos Cancer Hospital.

Funding

Department of Science and Technology–DECIT, Ministry of Health (grant no.879848/2018).

Disclosure

All authors have declared no conflicts of interest.