Significant impact of circulating tumour DNA mutations on survival in metastatic breast cancer patients

被引:18
作者
Muendlein, Axel [1 ]
Geiger, Kathrin [1 ,2 ]
Gaenger, Stella [1 ]
Dechow, Tobias [3 ]
Nonnenbroich, Christoph [3 ]
Leiherer, Andreas [1 ,2 ]
Drexel, Heinz [1 ,4 ]
Gaumann, Andreas [5 ]
Jagla, Wolfgang [5 ]
Winder, Thomas [6 ]
Mayer, Frank [7 ]
Decker, Thomas [3 ]
机构
[1] Vorarlberg Inst Vasc Investigat & Treatment, Mol Biol Lab, Stadtstr 33, A-6850 Mol, Austria
[2] Med Cent Labs, A-6800 Feldkirch, Austria
[3] Onkol Ravensburg, D-88212 Ravensburg, Germany
[4] Hosp Bregenz, Dept Internal Med, A-6900 Bregenz, Austria
[5] Inst Pathol Kaufbeuren Ravensburg, D-87600 Kaufbeuren, Germany
[6] Acad Teaching Hosp Feldkirch, Dept Haematol & Oncol, A-6800 Feldkirch, Austria
[7] Praxis & Tagesklinik, Prof Dr Oettle Helmut & Prof Dr Dr Mayer Frank, D-88045 Friedrichshafen, Germany
关键词
D O I
10.1038/s41598-021-86238-7
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Mutational analysis of circulating tumour (ct) DNA holds promise as an effective tool to predict the course of metastatic breast cancer (MBC). In the present study we used targeted next generation sequencing of ctDNA to evaluate the impact of cancer driven mutations on the prognosis of MBC. The study included 59 oestrogen receptor-positive (ER+), HER2-negative MBC patients. Sequencing analysis was performed in ESR1, PIK3CA, ERBB2, PTEN, TP53, KRAS, HRAS, NRAS, and AR. At baseline, patients started receiving either chemotherapy (34%; n=20) or cyclin-dependent kinase 4/6 inhibitor therapy in combination with endocrine therapy (CDK4/6i+ET; 66%; n=39). Overall, 64.4% (n=38) of the patients carried at least one pathogenic or likely-pathogenic mutation. Number of ctDNA mutations was significantly linked with worse progression free survival (PFS; p=0.003) and overall survival (OS; p=0.007). Furthermore, ctDNA load, defined by the number of mutant ctDNA molecules per mL plasma, significantly correlated with PFS (p<0.001) and OS (p=0.001). Furthermore, mutational status of ESR1 and TP53 significantly predicted PFS (p=0.024 and p=0.035, respectively) and OS (p<0.001 and p=0.035, respectively). These results emphasizes the clinical value of ctDNA mutational analysis in the management of advanced breast cancer.
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页数:10
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