The tumor fraction of a cell-free DNA (cfDNA) sample may predict survival among patients with metastatic triple-negative breast cancer (TNBC), according to research published in the Journal of Clinical Oncology.1

While TNBC accounts for a little as 10% of breast cancer cases, the subtype is linked to more than a third of breast cancer–related deaths. Primary TNBC usually displays TP53 loss and a high number of somatic number copy alterations (SCNAs), suggesting that cfDNA profiling may be of prognostic value for this patient group.

For this study, researchers evaluated cfDNA data from 164 patients with metastatic TNBC to determine whether tumor fraction or particular SCNAs are prognostic for survival. Just over 500 plasma samples were collected and analyzed. All patients underwent chemotherapy prior to sampling.

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The median follow-up from diagnosis with metastatic disease was 17 months. Of the 164 enrolled patients, 101 had a tumor fraction of at least 10%; 63 had a tumor fraction of less than 10%. Patients in the high tumor fraction group had an inferior overall survival of 6.4 months compared with 15.9 months in the lower fraction group.

Despite other clinicopathologic factors, patients with a tumor fraction of 10% or greater were more than twice as likely to pass away as those with a fraction of less than 10% (hazard ratio, 2.14).

Metastatic TNBC samples, furthermore, displayed a higher frequency of SCNAs than did primary TNBC samples. Compared with primary samples, metastatic samples had high-frequency alterations of MYC, AKT3, GATA3, NOTCH2, EZH2, BRAF, and MET.

The authors concluded that this study “provides the most comprehensive genomic profile of metastatic TNBC SCNAs to date, to our knowledge, and suggests that determining cfDNA [tumor fraction] via a blood test provides important prognostic information beyond standard clinicopathologic factors.”


  1. Stover DG, Parsons HA, Ha G, et al. Association of cell-free DNA tumor fraction and somatic copy number alterations with survival in metastatic triple-negative breast cancer. J Clin Oncol. 2018 Jan 3. doi: 10.1200/JCO.2017.76.0033 [Epub ahead of print]