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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

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Journal of the National Cancer Center 2021年第3期1卷 115-121页

作者： Hongyuan Zhao Weijie Ma Ruben C.Fragoso Griffith R.Harsh IV Arya Ashok Tianhong Li Division of Hematology/Oncology Department of Internal MedicineUniversity of California Davis School of MedicineUniversity of California Davis Comprehensive Cancer CenterSacramentoUSA Current address:Department of Thyroid&Breast Surgery Affiliated Hospital of Zunyi Medical UniversityZunyiChina Department of Radiation Oncology University of California Davis School of MedicineUniversity of California Davis Comprehensive Cancer CenterSacramentoUSA Department of Neurological Surgery University of California Davis School of MedicineSacramentoUSA tempus labs Inc.ChicagoUSA

Patients with refractory metastatic triple-negative breast cancer(mTNBC)and symptomatic brain metastases have poor prognosis and are challenging to *** 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 *** clinical effi-cacy of the chemoimmunotherapy combination in patients with refractory mTNBC,especially brain metastasis,is ***-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 *** the utility of PDJ amplification as a biomarker predictive of response to PD-1/PD-L1 in-hibitors is unknown for mTNBC ***,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 ***-generation sequencing of her brain metastasis specimen revealed 9 copies of PDJ amplification and a tumor mutational burden of 5 mutations per *** high PDJ mRNA ex-pression levels were detected,PD-L1 protein expression was negative on tumor cells and 10%on tumor-associated immune *** 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 *** 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 *** study is warranted to understand the underlying mech-anism and validate PDJ amplification as a biomarker for clinica

关键词： Multidisciplinary Immune checkpoint inhibitor Pdj amplification Triple-negative breast cancer Brain metastasis

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