Purpose: The status of TP53  mutations was measured in cell-free DNA from patients with metastatic breast cancer (MBC) to investigate disease characteristics and the prognostic role of different locations of the TP53  mutation site.
Patients and Methods: Blood samples were taken from a total of 187 patients diagnosed with MBC who were treated at the Department of Breast Oncology, Peking University Cancer Hospital between January 2013 and March 2020. Next-generation sequencing was used to investigate the TP53  mutation spectra of circulating free DNA in these blood samples.
Results: Among the 187 MBC patients, TP53 -mutated patients had a significantly shorter median disease-free survival (DFS) and overall survival (OS) compared with TP53  wild-type patients (P=0.001 and P=0.006, respectively). Additionally, in hormone receptor positive/HER2 negative (HR+/HER2-) and triple negative (TNBC) cohorts, TP53 -mutated patients had a significantly shorter median DFS than TP53  wild-type patients (P=0.038 and P=0.023, respectively). The 79 patients with TP53  mutations carried 87 somatic TP53  mutations, of which most (77.0%) mapped to the DNA-binding domain (DBD) of the protein encoded by TP53  exons 5– 8. In patients with TP53  mutations, those occurring in the non-DBD had a significantly shorter median DFS and OS than TP53  wild type (P< 0.001 and P=0.001, respectively). Additionally, patients with non-missense mutations in the DBD had a significantly shorter median DFS and OS than TP53  wild-type patients (P=0.001 and P< 0.001, respectively). TP53 -mutated patients had a significantly shorter DFS than TP53  wild-type patients in the adjuvant endocrine therapy sensitive group (P=0.008), but differences in the endocrine therapy resistant group were not significant.
Conclusion: TP53 -mutated MBC patients had a significantly worse outcome than TP53  wild-type patients especially those in HR+/HER2– and TNBC cohorts. Of TP53 -mutated patients, those with non-missense mutations in the DBD had worse breast cancer-related survival. TP53  mutations were also associated with endocrine resistance.
Keywords: advanced breast cancer, TP53  mutation, NGS, adjuvant endocrine therapy, DNA-binding domain