Open AccessBRCA1 Reversion Mutation Confers Resistance to Olaparib and Camrelizumab in a Patient with Breast Cancer Liver Metastasis
Author(s) -
Jiani Pan,
Lei Lei,
Wei-Wu Ye,
Xiao-Jia Wang,
Wen Cao
Publication year - 2021
Publication title -
journal of breast cancer/journal of breast cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 36
eISSN - 2092-9900
pISSN - 1738-6756
DOI - 10.4048/jbc.2021.24.e39
Subject(s) - olaparib , medicine , reversion , cancer research , mutation , breast cancer , germline mutation , synthetic lethality , parp inhibitor , germline , oncology , cancer , genetics , polymerase , dna repair , poly adp ribose polymerase , biology , gene , phenotype
Reversion mutations are associated with clinical resistance to poly(ADP-ribose) polymerase inhibitors (PARPi). Here, we describe the detection of a BRCA1 reversion mutation in a 39-year-old woman with metastatic breast cancer harboring a heterozygous germline BRCA1 exons 7-8 deletion who received PARPi olaparib combined with immune checkpoint inhibitor camrelizumab as third-line therapy. During progression from the olaparib and camrelizumab combination therapy, we identified via genomic sequencing a novel 7-base pair somatic deletion in BRCA1 (c.617_623delACAAATC). Sequence analyses indicated that this mutation realigned the reading frame of BRCA1 , which potentially led to the reversal of its normal function and conferred resistance to PARPi.