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000128027 0247_ $$2doi$$a10.1007/s10549-014-2946-2
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000128027 0247_ $$2ISSN$$a0167-6806
000128027 0247_ $$2ISSN$$a1573-7217
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000128027 041__ $$aeng
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000128027 1001_ $$aMadhavan, Dharanija$$b0
000128027 245__ $$aPlasma DNA integrity as a biomarker for primary and metastatic breast cancer and potential marker for early diagnosis.060
000128027 260__ $$aDordrecht [u.a.]$$bSpringer Science + Business Media B.V.$$c2014
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000128027 520__ $$aCirculating 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.
000128027 536__ $$0G:(DE-HGF)POF3-313$$a313 - Cancer risk factors and prevention (POF3-313)$$cPOF3-313$$fPOF III$$x0
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000128027 650_7 $$2NLM Chemicals$$aBiomarkers, Tumor
000128027 7001_ $$aWallwiener, Markus$$b1
000128027 7001_ $$aBents, Karin$$b2
000128027 7001_ $$0P:(DE-HGF)0$$aZucknick, Manuela$$b3
000128027 7001_ $$aNees, Juliane$$b4
000128027 7001_ $$0P:(DE-HGF)0$$aSchott, Sarah$$b5
000128027 7001_ $$0P:(DE-HGF)0$$aCuk, Katarina$$b6
000128027 7001_ $$aRiethdorf, Sabine$$b7
000128027 7001_ $$0P:(DE-He78)732f4fbcddb0042251aa759a2e74d3b2$$aTrumpp, Andreas$$b8$$udkfz
000128027 7001_ $$aPantel, Klaus$$b9
000128027 7001_ $$aSohn, Christof$$b10
000128027 7001_ $$aSchneeweiss, Andreas$$b11
000128027 7001_ $$0P:(DE-He78)ec311cea9d07f894e44d05a570e26e28$$aSurowy, Harald$$b12$$udkfz
000128027 7001_ $$0P:(DE-He78)15b7fd2bc02d5ef47a2fe2dd0140d2bf$$aBurwinkel, Barbara$$b13$$eLast author$$udkfz
000128027 773__ $$0PERI:(DE-600)2004077-5$$a10.1007/s10549-014-2946-2$$gVol. 146, no. 1, p. 163 - 174$$n1$$p163 - 174$$tBreast cancer research and treatment$$v146$$x1573-7217$$y2014
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000128027 9141_ $$y2014
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