PURPOSE

The status of 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 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 mutation spectra of circulating free DNA in these blood samples.

RESULTS

Among the 187 MBC patients, -mutated patients had a significantly shorter median disease-free survival (DFS) and overall survival (OS) compared with 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, -mutated patients had a significantly shorter median DFS than wild-type patients (P=0.038 and P=0.023, respectively). The 79 patients with mutations carried 87 somatic mutations, of which most (77.0%) mapped to the DNA-binding domain (DBD) of the protein encoded by exons 5-8. In patients with mutations, those occurring in the non-DBD had a significantly shorter median DFS and OS than 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 wild-type patients (P=0.001 and P<0.001, respectively). -mutated patients had a significantly shorter DFS than 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

-mutated MBC patients had a significantly worse outcome than wild-type patients especially those in HR+/HER2- and TNBC cohorts. Of -mutated patients, those with non-missense mutations in the DBD had worse breast cancer-related survival. mutations were also associated with endocrine resistance.