ABSTRACT
Poly(ADP-ribose) polymerase inhibitors have been shown dramatic responses in patients with BRCAness. 

However, clinical studies have been limited to breast cancer patients with germline mutations. 

Here, we describe a patient with metastatic breast cancer who had a rare BRCA1 somatic mutation (BRCA1 c.4336G>T (p.E1446*)) detected by cell-free DNA analysis after failing standard therapies. 

This tier III variant of unknown significance was predicted to be a pathogenic variant in our assessment, leading us to consider off-label treatment with olaparib. 

The patient responded well to olaparib for several months, with a decrease in allele frequency of this BRCA1 somatic mutation in cfDNA. 

Olaparib resistance subsequently developed with an increase in the allele frequency and new BRCA1 reversion mutations. 

To our knowledge, this is the first report confirming BRCA1 c.4336G>T (p.E1446*) as a mutation sensitive to olaparib in breast cancer and describing the dynamic changes in the associated mutations using liquid biopsy.