Association of circulating tumor DNA with survival in neoadjuvant-treated triple negative breast cancer independent of pathological complete response.

Abstract

e12588 Background: Many patients with triple negative breast cancer (TNBC) still succumb to their disease after systematic treatment. It is crucial to identify those at high risk. Circulating tumor DNA (ctDNA) has recently become a promising marker to monitor tumor burden. Our study aimed to evaluate the clinical value of the presence and dynamic change of ctDNA to predict the tumor response and prognosis in TNBC patients treated with neoadjuvant chemotherapy (NAC). Methods: Cell-free DNA (cfDNA) was isolated from pre-NAC plasma samples and then analyzed by duplex sequencing. A Chi-square test or Fisher exact test were used for categorical variables. Kaplan‐Meier analysis with a Log‐rank test and the Cox proportional hazard regression model were used for the univariate and multivariable survival analysis. Survival prediction was assessed using a time-dependent receiver operating characteristic (ROC) curve and area under the ROC curve (AUC). Results: A total of 82 TNBC patients receiving NAC were enrolled. Baseline ctDNA detection indicated significantly worse survival. TP53 and genes involved in PI3K-Akt signaling pathway mutations were significantly associated with survival independent of the pathological complete response (pCR). A TP53 detection combined clinical model is highly predictive, with a time-dependent ROC of 0.936 for 3-year overall survival (OS), compared to the model including clinical variables only (AUC of the clinical predictor: 0.751, P= 0.028). Conclusions: Baseline ctDNA detection, TP53 mutations, and genes involved in PI3K-Akt signaling pathway mutation are all independent prognostic factors in TNBC patients receiving NAC. A TP53 detection combining model is highly predictive.