Efficacy of Olaparib in Treatment-Refractory, Metastatic Breast Cancer with Uncommon Somatic BRCA Mutations Detected in Circulating Tumor DNA.
Cancer Res Treat
; 55(3): 1048-1052, 2023 Jul.
Article
in En
| MEDLINE
| ID: mdl-36731462
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 cell-free DNA. 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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Breast Neoplasms
/
Cell-Free Nucleic Acids
/
Circulating Tumor DNA
Type of study:
Prognostic_studies
Limits:
Female
/
Humans
Language:
En
Journal:
Cancer Res Treat
Year:
2023
Document type:
Article