Prediction of breast tumor progression by integrity of free circulating DNA in serum.
OBJECTIVE
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.


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).


CONCLUSIONS
Integrity of serum circulating DNA is a promising molecular biomarker for detecting breast cancer tumor progression and regional LN metastases.
Umetani
Naoyuki
N
Department of Molecular Oncology and the Joyce Eisenberg Breast Center, John Wayne Cancer Institute, Santa Monica, CA 90404, USA.
Giuliano
Armando E
AE
Hiramatsu
Suzanne H
SH
Amersi
Farin
F
Nakagawa
Taku
T
Martino
Silvana
S
Hoon
Dave S B
DS
D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D004273:DNA, Neoplasm / Q000097:blood*; D018450:Disease Progression; D005260:Female; D006801:Humans; D016015:Logistic Models; D008207:Lymphatic Metastasis; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011237:Predictive Value of Tests; D012372:ROC Curve
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm