34P - A prognostic signature to predict recurrence in patients with residual disease in triple-negative breast cancer: NACATRINE trial

Background

Residual disease (RD) following neoadjuvant chemotherapy (NAC) poses a significant challenge in the treatment of triple-negative breast cancer (TNBC) due to its association with a worse prognosis. Our study aimed to investigate recurrence-related genes from the NACATRINE study. A phase II study evaluating the addition of carboplatin to standard of care NAC in early TNBC. The primary objective was establishing a genetic signature to predict disease-free survival (DFS) outcomes among TNBC patients with RD after NAC.

Methods

We conducted a differential gene expression analysis comparing patients who experienced recurrence to those who remained recurrence-free. Subsequently, we explored the association of these genes with DFS using a multivariate Cox model. Biopsy tissue samples were analyzed using the nCounter® Breast Cancer™ panel.

Results

We identified 58 genes that were differentially expressed among patients in our study. A total of ten genes (CCND2, GPX3, BNIP3, MYBL2, DLL3, UBE2C, HLA.DMB, TLR4, KAT2B, SLC2A1) exhibited an area under the curve (AUC) ≥ 0.70 when evaluated individually. Univariate Cox regression analysis showed that these genes had p-values <0.05. In the subsequent multivariate Cox model, CCND2, BNIP3, and MYBL2 remained significant, with a determination coefficient 0.70. This genetic signature demonstrated an AUC of 0.89, with a sensitivity of 0.87 and specificity of 0.87 in predicting recurrence.

Conclusions

In conclusion, our analysis identified three genes (CCND2, BNIP3, MYBL2) whose combination forms a predictive signature capable of identifying TNBC patients with RD at risk of relapse after NAC. These findings support the need for prospective clinical validation of this gene signature to refine prognostic strategies and potentially guide personalized treatment decisions in TNBC management.

Editorial acknowledgement

Clinical trial identification

NCT02978495.

Legal entity responsible for the study

The authors.

Funding

Department of Science and Technology-DECIT, Brazilian Ministry of Health (Grant No. 879848/2018).

Disclosure

All authors have declared no conflicts of interest.