Plasma cell-free DNA (cfDNA) as a predictive and prognostic marker in patients with metastatic breast cancer.

Autor: Fernandez-Garcia D; Leicester Cancer Research Centre, Department of Genetics and Genome Biology, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester, LE2 7LX, UK., Hills A; Department of Surgery and Cancer, Imperial College London, Du Cane Road, Hammersmith, London, W12 0NN, UK., Page K; Leicester Cancer Research Centre, Department of Genetics and Genome Biology, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester, LE2 7LX, UK., Hastings RK; Leicester Cancer Research Centre, Department of Genetics and Genome Biology, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester, LE2 7LX, UK., Toghill B; Leicester Cancer Research Centre, Department of Genetics and Genome Biology, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester, LE2 7LX, UK., Goddard KS; Department of Surgery and Cancer, Imperial College London, Du Cane Road, Hammersmith, London, W12 0NN, UK., Ion C; Imperial College London and Healthcare NHS Trust, Charing Cross Hospital, Fulham Palace Road, London, W6 8RF, UK., Ogle O; Welsh School of Pharmacy and Pharmaceutical Sciences, Redwood Building, King Edward VII Ave, Cardiff, CF10 3NB, UK., Boydell AR; Imperial College London and Healthcare NHS Trust, Charing Cross Hospital, Fulham Palace Road, London, W6 8RF, UK., Gleason K; Imperial College London and Healthcare NHS Trust, Charing Cross Hospital, Fulham Palace Road, London, W6 8RF, UK., Rutherford M; Department of Health Sciences, University of Leicester, George Davies Centre, Leicester, LE1 7RH, UK., Lim A; Imperial College London and Healthcare NHS Trust, Charing Cross Hospital, Fulham Palace Road, London, W6 8RF, UK., Guttery DS; Leicester Cancer Research Centre, Department of Genetics and Genome Biology, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester, LE2 7LX, UK., Coombes RC; Department of Surgery and Cancer, Imperial College London, Du Cane Road, Hammersmith, London, W12 0NN, UK., Shaw JA; Leicester Cancer Research Centre, Department of Genetics and Genome Biology, University of Leicester, Robert Kilpatrick Clinical Sciences Building, Leicester Royal Infirmary, Leicester, LE2 7LX, UK. js39@le.ac.uk.
Jazyk: angličtina
Zdroj: Breast cancer research : BCR [Breast Cancer Res] 2019 Dec 19; Vol. 21 (1), pp. 149. Date of Electronic Publication: 2019 Dec 19.
DOI: 10.1186/s13058-019-1235-8
Abstrakt: Background: Breast cancer (BC) is the most common cancer in women, and despite the introduction of new screening programmes, therapies and monitoring technologies, there is still a need to develop more useful tests for monitoring treatment response and to inform clinical decision making. The purpose of this study was to compare circulating cell-free DNA (cfDNA) and circulating tumour cells (CTCs) with conventional breast cancer blood biomarkers (CA15-3 and alkaline phosphatase (AP)) as predictors of response to treatment and prognosis in patients with metastatic breast cancer (MBC).
Methods: One hundred ninety-four female patients with radiologically confirmed MBC were recruited to the study. Total cfDNA levels were determined by qPCR and compared with CELLSEARCH® CTC counts and CA15-3 and alkaline phosphatase (AP) values. Blood biomarker data were compared with conventional tumour markers, treatment(s) and response as assessed by RECIST and survival. Non-parametric statistical hypothesis tests were used to examine differences, correlation analysis and linear regression to determine correlation and to describe its effects, logistic regression and receiver operating characteristic curve (ROC curve) to estimate the strength of the relationship between biomarkers and clinical outcomes and value normalization against standard deviation to make biomarker values comparable. Kaplan-Meier estimator and Cox regression models were used to assess survival. Univariate and multivariate models were performed where appropriate.
Results: Multivariate analysis showed that both the amount of total cfDNA (p value = 0.024, HR = 1.199, CI = 1.024-1.405) and the number of CTCs (p value = 0.001, HR = 1.243, CI = 1.088-1.421) are predictors of overall survival (OS), whereas total cfDNA levels is the sole predictor for progression-free survival (PFS) (p value = 0.042, HR = 1.193, CI = 1.007-1.415) and disease response when comparing response to non-response to treatment (HR = 15.917, HR = 12.481 for univariate and multivariate analysis, respectively). Lastly, combined analysis of CTCs and cfDNA is more informative than the combination of two conventional biomarkers (CA15-3 and AP) for prediction of OS.
Conclusion: Measurement of total cfDNA levels, which is a simpler and less expensive biomarker than CTC counts, is associated with PFS, OS and response in MBC, suggesting potential clinical application of a cheap and simple blood-based test.
Databáze: MEDLINE
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