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KMID : 0939920230550031048
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대한암학회지
2023 Volume.55 No. 3 p.1048 ~ p.1052
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Efficacy of Olaparib in Treatment-Refractory, Metastatic Breast Cancer with Uncommon Somatic BRCA Mutations Detected in Circulating Tumor DNA
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Yoon Jung-Ki
Ahn Jong-Seong
Kim Shee-Hyun
Kim Hwang-Phil
Kang Jun-kyu
Bang Du-Hee
Lim Yoo-Joo
Kim Tae-You
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Abstract
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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.
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KEYWORD
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Breast neoplasms, Cell-free nucleic acids, Liquid biopsy, Precision medicine
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