Reversion Mutation Confers Resistance to Olaparib and Camrelizumab in a Patient with Breast Cancer Liver Metastasis.

Reversion mutations are associated with clinical resistance to poly(ADP-ribose) polymerase inhibitors (PARPi). Here, we describe the detection of a reversion mutation in a 39-year-old woman with metastatic breast cancer harboring a heterozygous germline 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 (c.617_623delACAAATC). Sequence analyses indicated that this mutation realigned the reading frame of , which potentially led to the reversal of its normal function and conferred resistance to PARPi.