Journal Article

DKFZ-2018-00439

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Circulating free DNA integrity and concentration as independent prognostic markers in metastatic breast cancer.

Cheng, J. (First author)DKFZ* ; Holland-Letz, T.DKFZ* ; Wallwiener, M. ; Surowy, H.DKFZ* ; Cuk, K.DKFZ* ; Schott, S.DKFZ* ; Trumpp, A.DKFZ* ; Pantel, K. ; Sohn, C. ; Schneeweiss, A. ; Burwinkel, B. (Last author)DKFZ*

2018
Springer Science + Business Media B.V. Dordrecht [u.a.]

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Please use a persistent id in citations: doi:10.1007/s10549-018-4666-5

Abstract: Non-invasive blood-based molecular markers have been investigated for cancer diagnosis and prognosis. Circulating free or cell-free DNA (cfDNA) variables have been shown to be putative markers in breast cancer prognosis.Here, we investigated the potential prognostic ability of cfDNA concentration and cfDNA integrity (cfDI) in a study cohort of 268 patients by quantitative PCR. We compared cfDNA concentration and cfDI at baseline and after one cycle of therapy in metastatic breast cancer (MBC) patients.A significantly increased cfDI (P = 1.21E-7 for ALU and P = 1.87E-3 for LINE1) and decreased cfDNA concentration (P = 1.17E-3 for ALU and P = 1.60E-2 for LINE1) in both repetitive DNA elements after one cycle of therapy was observed. A multiple Cox regression model indicated that cfDI and cfDNA concentration can serve as independent prognostic markers in patients at baseline with HR (95% CI) of 0.70 (0.48-1.01) for ALU cfDI, 0.63 (0.44-0.92) for LINE1 cfDI, 2.44 (1.68-3.53) for ALU cfDNA concentration, and 2.12 (1.47-3.06) for LINE1 cfDNA concentration and after one cycle of therapy with HR (95% CI) of 0.59 (0.42-0.84) for ALU cfDI, 0.51 (0.36-0.74) for LINE1 cfDI, 1.59 (1.31-1.92) for ALU cfDNA concentration, and 1.30 (1.17-1.45) for LINE1 cfDNA concentration, respectively. By comparing integrated prediction error of different models, cfDNA variables were shown to improve the prognostic power of the CTC status.We hereby show that cfDNA variables, especially in combination with other markers, can serve as attractive prognostic markers for MBC patients at baseline and during the systematic therapy.

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Contributing Institute(s):

1. Molekulare Epidemiologie (C080)
2. Biostatistik (C060)
3. Stammzellen und Krebs (A010)
4. HI-Stem (V960)

Research Program(s):

1. 313 - Cancer risk factors and prevention (POF3-313) (POF3-313)

Appears in the scientific report 2018

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Database coverage:
; BIOSIS Previews ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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