BACKGROUND: Immunotherapy has demonstrated encouraging clinical benefits in 
patients with advanced breast carcinomas and Programmed death ligand 1 (PD-L1) 
expression has been proposed as an immunotherapy biomarker. Challenges with 
current PD-L1 testing exist and tumor mutation burden (TMB) is emerging as a 
biomarker to predict clinical response to immunotherapy in melanoma and 
non-small cell lung cancer patients. However, TMB has not been well 
characterized in breast carcinomas.
METHODS: The study cohort included 62 advanced breast cancer patients (13 
primary and 49 metastatic). Genetic alterations and TMB were determined by 
FoundationOne CDx next generation sequencing (NGS) and the association with 
clinicopathologic features was analyzed.
RESULTS: High TMB was observed in a relatively low frequency (3/62, 4.8%). TMB 
levels were positively associated tumor infiltrating lymphocytes and 
significantly higher TMB was observed in breast carcinomas with DNA damage 
repair gene mutation(s). There was no significant association between TMB levels 
and other analyzed clinicopathologic characteristics.
CONCLUSIONS: Our data indicate the importance of DNA damage repair proteins in 
maintaining DNA integrity and immune reaction and breast carcinoma patients with 
DDR mutation may benefit from immunotherapy.