Clinical spectrum and prognostic value of TP53 mutations in circulating tumor DNA from breast cancer patients in China

Abstract Background TP53 mutations are common in breast cancer. There is currently no large‐scale cohort study to investigate the TP53 landscape in breast cancer patients from China. The predictive value of TP53 mutations for the efficacy of human epidermal growth factor receptor 2 (HER2)‐targeted therapy in breast cancer remains controversial. In the present study, we aimed to analyze the clinical spectrum and prognostic value of TP53 mutations in circulating tumor DNA (ctDNA) from breast cancer patients in China. Methods We retrospectively analyzed the clinical data and TP53 mutation features in ctDNA samples from 804 patients with metastatic breast cancer. TP53 mutations were detected by target region capture‐based next‐generation sequencing. The relationship between TP53 mutation status and disease‐free survival (DFS) was analyzed in 444 patients with metastatic breast cancer. Moreover, the relationship between TP53 mutation status and progression‐free survival (PFS) was analyzed in 55 HER2‐positive patients treated with first‐line trastuzumab‐based therapy. Kaplan‐Meier analysis was performed to estimate the survival curves of the different subgroups, and the log‐rank test was used to compare the curves. A Cox regression model was used to estimate multivariable‐adjusted hazard ratios and their 95% confidence intervals (CIs) associated with the DFS and PFS. Results Among the 804 investigated patients, 431 (53.6%) patients harbored TP53 mutations. TP53 mutations were differentially distributed among different molecular subtypes of breast cancer (P