Plasma DNA integrity as a biomarker for primary and metastatic breast cancer and potential marker for early diagnosis
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Plasma DNA integrity as a biomarker for primary and metastatic breast cancer and potential marker for early diagnosis. / Madhavan, Dharanija; Wallwiener, Markus; Bents, Karin; Zucknick, Manuela; Nees, Juliane; Schott, Sarah; Cuk, Katarina; Riethdorf, Sabine; Trumpp, Andreas; Pantel, Klaus; Sohn, Christof; Schneeweiss, Andreas; Surowy, Harald; Burwinkel, Barbara.
In: BREAST CANCER RES TR, Vol. 146, No. 1, 01.07.2014, p. 163-174.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Plasma DNA integrity as a biomarker for primary and metastatic breast cancer and potential marker for early diagnosis
AU - Madhavan, Dharanija
AU - Wallwiener, Markus
AU - Bents, Karin
AU - Zucknick, Manuela
AU - Nees, Juliane
AU - Schott, Sarah
AU - Cuk, Katarina
AU - Riethdorf, Sabine
AU - Trumpp, Andreas
AU - Pantel, Klaus
AU - Sohn, Christof
AU - Schneeweiss, Andreas
AU - Surowy, Harald
AU - Burwinkel, Barbara
PY - 2014/7/1
Y1 - 2014/7/1
N2 - Circulating or cell-free DNA (cfDNA) has been evaluated as a biomarker in many cancers including breast cancer. In particular, integrity of cfDNA has been shown to be altered in cancers. We have estimated the biomarker potential of cfDNA in primary (PBC) and metastatic breast cancer (MBC). cfDNA integrity (cfDI) and concentration were determined in plasma of 383 individuals, including 82 PBC and 201 MBC cases, as well as 100 healthy controls, by measuring ALU and LINE1 repetitive DNA elements using quantitative PCR. The MBC patient group was further sub-divided into patients with detectable circulating tumour cells (CTCpos-MBC, n = 100) and those without (CTCneg-MBC, n = 101). A hierarchical decrease in cfDI and increase in cfDNA concentration from healthy controls to PBC and further onto MBC patients were observed. Investigation of cfDNA in media of cell lines was in concordance with these results. Combination of cfDI and cfDNA concentration could differentiate PBC cases from controls (area under the curve, AUC = 0.75), MBC cases from controls (AUC = 0.81 for CTCneg-MBC, AUC = 0.93 for CTCpos-MBC), and CTCneg-MBC from CTCpos-MBC cases (AUC = 0.83). cfDI additionally demonstrated a positive correlation to progression-free (HR of 0.46 for ALU, P = 0.0025) and overall survival (HR of 0.15 for ALU and 0.20 for LINE1, P < 0.0001) in MBC, and had lower prediction error than CTC status. Our findings show that reduced cfDI and increased cfDNA concentration can serve as diagnostic markers for PBC and MBC, and cfDI as a prognostic marker for MBC, thereby making them attractive candidates for blood-based multi-marker assays.
AB - Circulating or cell-free DNA (cfDNA) has been evaluated as a biomarker in many cancers including breast cancer. In particular, integrity of cfDNA has been shown to be altered in cancers. We have estimated the biomarker potential of cfDNA in primary (PBC) and metastatic breast cancer (MBC). cfDNA integrity (cfDI) and concentration were determined in plasma of 383 individuals, including 82 PBC and 201 MBC cases, as well as 100 healthy controls, by measuring ALU and LINE1 repetitive DNA elements using quantitative PCR. The MBC patient group was further sub-divided into patients with detectable circulating tumour cells (CTCpos-MBC, n = 100) and those without (CTCneg-MBC, n = 101). A hierarchical decrease in cfDI and increase in cfDNA concentration from healthy controls to PBC and further onto MBC patients were observed. Investigation of cfDNA in media of cell lines was in concordance with these results. Combination of cfDI and cfDNA concentration could differentiate PBC cases from controls (area under the curve, AUC = 0.75), MBC cases from controls (AUC = 0.81 for CTCneg-MBC, AUC = 0.93 for CTCpos-MBC), and CTCneg-MBC from CTCpos-MBC cases (AUC = 0.83). cfDI additionally demonstrated a positive correlation to progression-free (HR of 0.46 for ALU, P = 0.0025) and overall survival (HR of 0.15 for ALU and 0.20 for LINE1, P < 0.0001) in MBC, and had lower prediction error than CTC status. Our findings show that reduced cfDI and increased cfDNA concentration can serve as diagnostic markers for PBC and MBC, and cfDI as a prognostic marker for MBC, thereby making them attractive candidates for blood-based multi-marker assays.
U2 - 10.1007/s10549-014-2946-2
DO - 10.1007/s10549-014-2946-2
M3 - SCORING: Journal article
C2 - 24838941
VL - 146
SP - 163
EP - 174
JO - BREAST CANCER RES TR
JF - BREAST CANCER RES TR
SN - 0167-6806
IS - 1
ER -