Research Papers:

Cell-free DNA detected by “liquid biopsy” as a potential prognostic biomarker in early breast cancer

Roberta Maltoni, Valentina Casadio, Sara Ravaioli, Flavia Foca, Maria Maddalena Tumedei, Samanta Salvi, Filippo Martignano, Daniele Calistri, Andrea Rocca, Alessio Schirone, Dino Amadori and Sara Bravaccini _

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Oncotarget. 2017; 8:16642-16649. https://doi.org/10.18632/oncotarget.15120

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Roberta Maltoni1, Valentina Casadio2,*, Sara Ravaioli2,*, Flavia Foca3, Maria Maddalena Tumedei2, Samanta Salvi2, Filippo Martignano2, Daniele Calistri2, Andrea Rocca1, Alessio Schirone1, Dino Amadori1, Sara Bravaccini2

1Department of Medical Oncology, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

2Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

3Unit of Biostatistics and Clinical Trials, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy

*These authors contributed equally to this work

Correspondence to:

Sara Bravaccini, email: [email protected]

Keywords: CF-DNA, HER2, PI3KCA, prognosis, breast cancer subtypes

Received: August 20, 2016     Accepted: January 23, 2017     Published: February 06, 2017


As conventional biomarkers for defining breast cancer (BC) subtypes are not always capable of predicting prognosis, search for new biomarkers which can be easily detected by liquid biopsy is ongoing. It has long been known that cell-free DNA (CF-DNA) could be a promising diagnostic and prognostic marker in different tumor types, although its prognostic value in BC is yet to be confirmed. This retrospective study evaluated the prognostic role of CF-DNA quantity and integrity of HER2, MYC, BCAS1 and PI3KCA, which are frequently altered in BC. We collected 79 serum samples before surgery from women at first diagnosis of BC at Forlì Hospital (Italy) from 2002 to 2010. Twenty-one relapsed and 58 non-relapsed patients were matched by subtype and age. Blood samples were also collected from 10 healthy donors. All samples were analyzed by Real Time PCR for CF-DNA quantity and integrity of all oncogenes. Except for MYC, BC patients showed significantly higher median values of CF-DNA quantity (ng) than healthy controls, who had higher integrity and lower apoptotic index. A difference nearing statistical significance was observed for HER2 short CF-DNA (p = 0.078, AUC value: 0.6305). HER2 short CF-DNA showed an odds ratio of 1.39 for disease recurrence with p = 0.056 (95% CI 0.991-1.973). Our study suggests that CF-DNA detected as liquid biopsy could have great potential in clinical practice once demonstration of its clinical validity and utility has been provided by prospective studies with robust assays.

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