Durable clinical response to the multidisciplinary management of neurosurgery,radiation and chemoimmunotherapy in a patient with PD-L1/PD-L2/JAK2(PDJ)-amplified,refractory triple-negative breast cancer  

作　　者：Hongyuan Zhao Weijie Ma Ruben C.Fragoso Griffith R.Harsh IV Arya Ashok Tianhong Li 

机构地区：[1]Division of Hematology/Oncology,Department of Internal Medicine,University of California Davis School of Medicine,University of California Davis Comprehensive Cancer Center,Sacramento,USA [2]Current address:Department of Thyroid&Breast Surgery,Affiliated Hospital of Zunyi Medical University,Zunyi,China [3]Department of Radiation Oncology,University of California Davis School of Medicine,University of California Davis Comprehensive Cancer Center,Sacramento,USA [4]Department of Neurological Surgery,University of California Davis School of Medicine,Sacramento,USA [5]Tempus Labs,Inc.,Chicago,USA

出　　处：《Journal of the National Cancer Center》2021年第3期115-121,共7页癌症科学进展（英文）

摘　　要：Patients with refractory metastatic triple-negative breast cancer(mTNBC)and symptomatic brain metastases have poor prognosis and are challenging to treat.The addition of an programmed cell death-1(PD-1)/programmed cell death-ligand 1(PD-L1)inhibitor(pembrolizumab or atezolizumab)to first line chemotherapy has prolonged survivals in mTNBC patients with PD-L1-positive tumor and/or tumor-infiltrating immune cells.The clinical effi-cacy of the chemoimmunotherapy combination in patients with refractory mTNBC,especially brain metastasis,is unknown.Co-amplification of PD-L1,PD-L2,and Janus kinase 2(PD-L1/PD-L2/JAK2)genes(PDJ amplification)is associated with high PD-L1 protein expression and a 65-87%response rate to PD-1/PD-L1 inhibitors in patients with lymphomas.But the utility of PDJ amplification as a biomarker predictive of response to PD-1/PD-L1 in-hibitors is unknown for mTNBC patients.Here,we report a 46-year-old woman who had rapid tumor progression in the brain and lung within 3 months after chemotherapy,neurosurgery,and gamma knife stereotactic radio-surgery for brain metastasis.Next-generation sequencing of her brain metastasis specimen revealed 9 copies of PDJ amplification and a tumor mutational burden of 5 mutations per megabase.Although high PDJ mRNA ex-pression levels were detected,PD-L1 protein expression was negative on tumor cells and 10%on tumor-associated immune cells.After the debulking brain tumor resection,she received pembrolizumab monotherapy,whole brain radiation,and then atezolizumab and nab-paclitaxel with good intracranial and extracranial responses for>16 months.To the best of our knowledge,this is the first report that PDJ amplification is associated with durable clin-ical response to the PD-1/PD-L1 inhibitor-containing,multidisciplinary management in a patient with refractory,PD-L1 protein-negative,PDJ-amplified mTNBC.Further study is warranted to understand the underlying mech-anism and validate PDJ amplification as a biomarker for clinical response to PD-1/PD-L1 inhibitor-containing th

关 键 词：Multidisciplinary Immune checkpoint inhibitor Pdj amplification Triple-negative breast cancer Brain metastasis 

分 类 号：R73[医药卫生—肿瘤]