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

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 lin...

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Autores principales:	Hongyuan Zhao, Weijie Ma, Ruben C. Fragoso, Griffith R. Harsh IV, Arya Ashok, Tianhong Li
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Multidisciplinary Immune checkpoint inhibitor Pdj amplification Triple-negative breast cancer Brain metastasis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/b0207e3a22944f94890d61ef2e6ba3ed
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spelling	oai:doaj.org-article:b0207e3a22944f94890d61ef2e6ba3ed2021-12-01T05:06:51ZDurable 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 cancer2667-005410.1016/j.jncc.2021.07.004https://doaj.org/article/b0207e3a22944f94890d61ef2e6ba3ed2021-09-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2667005421000338https://doaj.org/toc/2667-0054Patients 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 efficacy 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 inhibitors 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 radiosurgery 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 expression 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 clinical 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 mechanism and validate PDJ amplification as a biomarker for clinical response to PD-1/PD-L1 inhibitor-containing therapy in patients with mTNBC.Hongyuan ZhaoWeijie MaRuben C. FragosoGriffith R. Harsh IVArya AshokTianhong LiElsevierarticleMultidisciplinaryImmune checkpoint inhibitorPdj amplificationTriple-negative breast cancerBrain metastasisNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENJournal of the National Cancer Center, Vol 1, Iss 3, Pp 115-121 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Multidisciplinary Immune checkpoint inhibitor Pdj amplification Triple-negative breast cancer Brain metastasis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Multidisciplinary Immune checkpoint inhibitor Pdj amplification Triple-negative breast cancer Brain metastasis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Hongyuan Zhao Weijie Ma Ruben C. Fragoso Griffith R. Harsh IV Arya Ashok Tianhong Li 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
description	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 efficacy 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 inhibitors 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 radiosurgery 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 expression 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 clinical 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 mechanism and validate PDJ amplification as a biomarker for clinical response to PD-1/PD-L1 inhibitor-containing therapy in patients with mTNBC.
format	article
author	Hongyuan Zhao Weijie Ma Ruben C. Fragoso Griffith R. Harsh IV Arya Ashok Tianhong Li
author_facet	Hongyuan Zhao Weijie Ma Ruben C. Fragoso Griffith R. Harsh IV Arya Ashok Tianhong Li
author_sort	Hongyuan Zhao
title	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
title_short	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
title_full	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
title_fullStr	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
title_full_unstemmed	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
title_sort	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
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/b0207e3a22944f94890d61ef2e6ba3ed
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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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