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Sci Transl Med. 2015 Aug 26;7(302):302ra133. doi: 10.1126/scitranslmed.aab0021.

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

Author information

1
Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK.
2
Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK. Breast Unit, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK.
3
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
4
Institute of Cancer Research Clinical Trials and Statistics Unit, The Institute of Cancer Research, 15 Cotswold Road, Surrey SM2 5NG, UK.
5
Breast Unit, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK.
6
Breakthrough Breast Cancer Research Centre, The Institute of Cancer Research, Fulham Road, London SW3 6JB, UK. Breast Unit, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK. nicholas.turner@icr.ac.uk.

Abstract

The identification of early-stage breast cancer patients at high risk of relapse would allow tailoring of adjuvant therapy approaches. We assessed whether analysis of circulating tumor DNA (ctDNA) in plasma can be used to monitor for minimal residual disease (MRD) in breast cancer. In a prospective cohort of 55 early breast cancer patients receiving neoadjuvant chemotherapy, detection of ctDNA in plasma after completion of apparently curative treatment-either at a single postsurgical time point or with serial follow-up plasma samples-predicted metastatic relapse with high accuracy [hazard ratio, 25.1 (confidence interval, 4.08 to 130.5; log-rank P < 0.0001) or 12.0 (confidence interval, 3.36 to 43.07; log-rank P < 0.0001), respectively]. Mutation tracking in serial samples increased sensitivity for the prediction of relapse, with a median lead time of 7.9 months over clinical relapse. We further demonstrated that targeted capture sequencing analysis of ctDNA could define the genetic events of MRD, and that MRD sequencing predicted the genetic events of the subsequent metastatic relapse more accurately than sequencing of the primary cancer. Mutation tracking can therefore identify early breast cancer patients at high risk of relapse. Subsequent adjuvant therapeutic interventions could be tailored to the genetic events present in the MRD, a therapeutic approach that could in part combat the challenge posed by intratumor genetic heterogeneity.

PMID:
26311728
DOI:
10.1126/scitranslmed.aab0021
[Indexed for MEDLINE]

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