PURPOSE: Cell-free DNA circulating in serum is a candidate molecular biomarker for malignant tumors. Unlike uniformly truncated DNA released from apoptotic cells, DNA released from dead cancer cells varies in size. Serum DNA integrity, the ratio of longer fragments to total DNA, may be clinically useful for detecting breast cancer progression. PATIENTS AND METHODS: Serum samples from 51 healthy females and 83 females with primary breast cancers (eight American Joint Committee on Cancer stage 0, 24 stage I, 27 stage II, 21 stage III, and three stage IV) were assessed preoperatively. Serum DNA integrity was assessed by fragment length-dependent quantitative real-time polymerase chain reaction of ALU DNA repeats. RESULTS: Mean serum DNA integrity was significantly higher in patients with stage II, III, and IV breast cancers than in healthy females (P = .005, P < .0001, and P = .002, respectively). The receiver operating characteristic (ROC) curve for discriminating patients with stage II or more advanced breast cancers from healthy females had an area under the curve (AUC) of 0.79 (95% CI, 0.70 to 0.86). Mean serum DNA integrity was positively correlated to size of invasive cancers (r = 0.48; P < .0001) and significantly higher in the presence of lymphovascular invasion (LVI; 0.25 +/- 0.02 v 0.17 +/- 0.02; P < .0001) or lymph node (LN) metastasis (0.27 +/- 0.02 v 0.14 +/- 0.02; P < .0001). The ROC curve for discriminating LN metastasis had an AUC of 0.81 (95% CI, 0.72 to 0.89). Serum DNA integrity and LVI were significant for predicting LN metastasis in a multivariate analysis (P = .0002 and P < .0001, respectively). CONCLUSION: Integrity of serum circulating DNA is a promising molecular biomarker for detecting breast cancer tumor progression and regional LN metastases.
PURPOSE: Cell-free DNA circulating in serum is a candidate molecular biomarker for malignant tumors. Unlike uniformly truncated DNA released from apoptotic cells, DNA released from dead cancer cells varies in size. Serum DNA integrity, the ratio of longer fragments to total DNA, may be clinically useful for detecting breast cancer progression. PATIENTS AND METHODS: Serum samples from 51 healthy females and 83 females with primary breast cancers (eight American Joint Committee on Cancer stage 0, 24 stage I, 27 stage II, 21 stage III, and three stage IV) were assessed preoperatively. Serum DNA integrity was assessed by fragment length-dependent quantitative real-time polymerase chain reaction of ALU DNA repeats. RESULTS: Mean serum DNA integrity was significantly higher in patients with stage II, III, and IV breast cancers than in healthy females (P = .005, P < .0001, and P = .002, respectively). The receiver operating characteristic (ROC) curve for discriminating patients with stage II or more advanced breast cancers from healthy females had an area under the curve (AUC) of 0.79 (95% CI, 0.70 to 0.86). Mean serum DNA integrity was positively correlated to size of invasive cancers (r = 0.48; P < .0001) and significantly higher in the presence of lymphovascular invasion (LVI; 0.25 +/- 0.02 v 0.17 +/- 0.02; P < .0001) or lymph node (LN) metastasis (0.27 +/- 0.02 v 0.14 +/- 0.02; P < .0001). The ROC curve for discriminating LN metastasis had an AUC of 0.81 (95% CI, 0.72 to 0.89). Serum DNA integrity and LVI were significant for predicting LN metastasis in a multivariate analysis (P = .0002 and P < .0001, respectively). CONCLUSION: Integrity of serum circulating DNA is a promising molecular biomarker for detecting breast cancer tumor progression and regional LN metastases.
Authors: Florent Mouliere; Dineika Chandrananda; Anna M Piskorz; Elizabeth K Moore; James Morris; Lise Barlebo Ahlborn; Richard Mair; Teodora Goranova; Francesco Marass; Katrin Heider; Jonathan C M Wan; Anna Supernat; Irena Hudecova; Ioannis Gounaris; Susana Ros; Mercedes Jimenez-Linan; Javier Garcia-Corbacho; Keval Patel; Olga Østrup; Suzanne Murphy; Matthew D Eldridge; Davina Gale; Grant D Stewart; Johanna Burge; Wendy N Cooper; Michiel S van der Heijden; Charles E Massie; Colin Watts; Pippa Corrie; Simon Pacey; Kevin M Brindle; Richard D Baird; Morten Mau-Sørensen; Christine A Parkinson; Christopher G Smith; James D Brenton; Nitzan Rosenfeld Journal: Sci Transl Med Date: 2018-11-07 Impact factor: 17.956
Authors: Peiyong Jiang; Carol W M Chan; K C Allen Chan; Suk Hang Cheng; John Wong; Vincent Wai-Sun Wong; Grace L H Wong; Stephen L Chan; Tony S K Mok; Henry L Y Chan; Paul B S Lai; Rossa W K Chiu; Y M Dennis Lo Journal: Proc Natl Acad Sci U S A Date: 2015-02-02 Impact factor: 11.205
Authors: Johanna Tuomela; Jouko Sandholm; Mika Kaakinen; Ankita Patel; Joonas H Kauppila; Joanna Ilvesaro; Dongquan Chen; Kevin W Harris; David Graves; Katri S Selander Journal: Breast Cancer Res Treat Date: 2013-11-10 Impact factor: 4.872