Mutation tracking in circulating tumor DNA predicts relapse in early breast cancer

Isaac Garcia-Murillas1,*,
Gaia Schiavon1,2,*,†,
Britta Weigelt3,
Charlotte Ng3,
Sarah Hrebien1,
Rosalind J. Cutts1,
Maggie Cheang4,
Peter Osin2,
Ashutosh Nerurkar2,
Iwanka Kozarewa1,
Javier Armisen Garrido1,
Mitch Dowsett1,2,
Jorge S. Reis-Filho3,
Ian E. Smith2 and
Nicholas C. Turner1,2,‡

+ Author Affiliations

↵‡Corresponding author. E-mail: nicholas.turner@icr.ac.uk

↵* These authors contributed equally to this work.
↵† Present address: Translational Science, Oncology iMed, AstraZeneca, Cambridge CB4 0WG, UK.

Science Translational Medicine 26 Aug 2015:
Vol. 7, Issue 302, pp. 302ra133
DOI: 10.1126/scitranslmed.aab0021

Risk of recurrence

Predicting whether a cancer patient will relapse remains a formidable challenge in modern medicine. Fortunately, circulating tumor DNA (ctDNA) present in the blood may give clues on residual disease—cancer cells left behind to seed new tumors even after treatment. Garcia-Murillas et al. developed a personalized ctDNA assay based on digital polymerase chain reaction to track mutations over time in patients with early-stage breast cancer who had received apparently curative treatments, surgery, and chemotherapy. Mutation tracking in serial samples accurately predicted metastatic relapse—in several instances, months before clinical relapse (median of ~8 months). Such unprecedented early prediction could allow for intervention before the reappearance of cancer in high-risk patients. In addition, the authors were able to shed light on the genetic events driving such metastases, by massively parallel sequencing of the ctDNA, which could inform new drug-based therapies on the basis of the patients’ individual mutations.