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Efficacy of platinum in advanced triple-negative breast cancer with germline brca mutation determined by next generation sequencing

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Chinese Journal of Cancer Research 2020年第2期32卷 149-162页

作者： Nan Wang Kun Li Wenfa Huang Weiyao Kong Xiaoran Liu Weijie Shi Feng Xie Hanfang Jiang Guohong Song Lijun Di Quanren Wang Jianjun Yu Huiping Li Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Breast OncologyPeking University Cancer Hospital and InstituteBeijing 100142China Huidu Shanghai Medical Sciences Shanghai 201499China Jiangsu Hengrui Medicine Shanghai 200120China

Objective:To compare the efficacy of platinum-and non-platinum-based regimens as first-line treatment for advanced triple-negative breast cancer(TNBC)and analyze the relationship between their efficacy and brca gene ***:Retrospectively analyze clinical data of 220 patients diagnosed pathologically with advanced TNBC and treated at the Department of Breast Oncology,Peking University Cancer Hospital from 2013 to 2018 and evaluate the efficacy of chemotherapy.A total of 114 patients had brca1/2 gene tested by next generation sequencing(NGS)using peripheral blood,and we analyzed the correlation between their efficacy and brca1/2 gene ***:Non-platinum-based chemotherapy(NPCT)was administered to 129 and platinum-based chemotherapy(PBCT)to 91 study *** clinical benefit rate(CBR)and median progression-free survival(PFS)were not statistically different between NPCT and PBCT *** median overall survival(OS)was 30.0 and 22.5 months for PBCT and NPCT group,respectively[P=0.090,hazard ratios(HR)=0.703].brca status was assessed in 114 patients,14 of whom had deleterious germline brca1/2(g brca)mutations(seven in each group).In PBCT group,the CBR was 85.7%and 35.1%for patients with and without deleterious g brca mutations,respectively(P=0.039).The median PFS were 14.9 and 5.3 months and median OS were 26.5 and 15.5 months for patients with and without deleterious g brca mutations,respectively(P=0.001,P=0.161,respectively).Patients in PBCT group had significantly greater rates of grade 3-4 anemia(5.5%vs.0%)and thrombocytopenia(8.8%vs.0%),whereas palmar-plantar erythrodysesthesia(12.4%vs.0%)and peripheral neuropathy(8.6%vs.1.1%)occurred more frequently in NPCT ***:Platinum-based regimens are more effective in patients with deleterious g brca mutations,but no difference in patients without brca gene mutations,so non-platinum is an option in patients without brca gene mutations considering the toxicity and side *** we recommend

关键词： Advanced breast cancer triple negative brca mutation next-generation sequencing platinum efficacy

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The Achilles’ Heel of Pancreatic Cancer: Targeting pancreatic cancer’s unique immunologic characteristics and metabolic dependencies in clinical trials

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Journal of Pancreatology 2020年第3期3卷 121-131页

作者： Despina Siolas Christy Morrissey Paul E.Oberstein Department of Medicine Perlmutter Comprehensive Cancer CenterNYU Langone HealthNew YorkNYUSA

Pancreatic ductal adenocarcinoma(PDAC)has a high mortality rate and is notoriously refractory to multiple cancer *** recent years,cancer therapy has expanded beyond traditional cytotoxic chemotherapy to targeted agents and immunotherapy which have been successfully implemented in many *** robust pre-clinical research,these novel therapies have only had a small impact on ***,there have been successes with emerging clinical data supporting a potential role for checkpoint inhibitor therapy and targeted therapy with poly(ADP-ribose)polymerase inhibitors for select subsets of PDAC *** this clinical review,we discuss recent pre-clinical evidence for targeting metabolic pathways as well as prevalent intratumoral immune subsets,and focus on clinical trials designed to test novel agents in *** challenge of translating pre-clinical findings to patients remains substantial and many clinical trials yield negative results,but collaborative efforts and renewed focus on novel clinical trials have led to optimism that we will identify additional options for PDAC patients and change outcomes for this deadly disease.

关键词： brca mutation Clinical trials Immunotherapy Pancreatic cancer Targeted therapy Tumor-associated macrophages

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