To the Editor The study by Garcia-Murillas and colleagues1 suggests an association of detection of circulating tumor DNA (ctDNA) in patients treated for early-stage breast cancer with a high risk of disease recurrence. The authors conclude that 23 of 29 recurrences (79%) were ctDNA positive and that the mean clinical lead time between detection of ctDNA and relapse was 10.7 months (95% CI, 8.1-19.1 months). Garcia-Murillas et al1 also found an association of detection of ctDNA at diagnosis with relapse-free survival (hazard ratio, 5.8; 95% CI, 1.2-27.1). They have shown that ctDNA levels varied in all breast cancer subtypes and were highest in triple-negative cancers, intermediate in ERBB2-positive cancers, and lowest in the estrogen receptor– and progesterone receptor–positive cancers. The presence of ctDNA during follow-up was associated with a shorter relapse-free period in all subtypes. The study validates the method of analyzing ctDNA by personalized digital polymerase chain reaction, in which the tumor mutations are assessed first and then similar mutations are searched for in the plasma of the patient on follow-up to detect molecular residual disease.