Table 1.
Published studies on cfDNA monitoring in MBC.
| Detection | First Author | Year | Method | Target(s) | Baseline | % | Longitudinal | % | Correlative | Measurement | Determined by | Risk of Bias (QUIPS) |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mutation | J.A. Garcia-Saenz [16] | 2017 | dPCR | PIK3CA | 8/32 | 25.0% | 8/8 * | 100.0% | Partial | Continuous | RECIST, PTM | Low |
| W. Jacot [17] | 2019 | dPCR | PIK3CA | 10/36 | 27.8% | 10/36 | 27.8% | Yes | Endpoint | RECIST | Low | |
| A.R. Kodahl [18] | 2018 | dPCR | PIK3CA | 20/60 | 33.3% | 4/6 * | 66.7% | Yes | Continuous | RECIST | Moderate | |
| X. Li [19] | 2020 | NGS | ESR1 | 9/45 | 20.0% | 5/5 * | 100.0% | Partial | Continuous | RECIST, PTM | Moderate | |
| P. Wang [20] | 2015 | dPCR | ESR1 | 7/29 | 24.1% | 4/4 * | 100.0% | Yes | Continuous | PTM | Moderate | |
| S.R. Vitale [21] | 2018 | dPCR | ESR1 | 3/67 | 4.5% | 4/17 | 23.5% | Yes | Continuous | Not defined | Moderate | |
| C. Paoletti [22] | 2018 | dPCR | ESR1 | 14/45 | 31.1% | 17/45 | 37.8% | Yes | Endpoint | RECIST, PTM | Low | |
| D. Sefrioui [23] | 2015 | dPCR | ESR1 | 4/7 | 57.1% | 4/7 | 57.1% | Yes | Continuous | Not defined | Low | |
| E. Jeannot [24] | 2020 | dPCR | ESR1 | 17/59 | 28.8% | 15/15 * | 100.0% | Yes | Endpoint | RECIST | Low | |
| F. Clatot + [15] | 2020 | dPCR | ESR1 | 22/70 | 31.4% | 22/22 * | 100.0% | Yes | Continuous | RECIST | Low | |
| T. Takeshita [25] | 2016 | dPCR | ESR1 | 12/42 | 28.6% | 12/42 | 28.6% | Yes | Both | RECIST, CA 15-3, CEA | Low | |
| T. Takeshita [26] | 2017 | dPCR | PIK3CA | 17/69 | 24.6% | 21/52 | 40.4% | No | Both | RECIST | Low | |
| ““ | ESR1 | 20/69 | 29.0% | 24/52 | 46.2% | Yes | Both | ““ | ||||
| J.M. Spoerke [27] | 2016 | dPCR | PIK3CA | 62/156 | 39.7% | 41/60 | 68.3% | Yes | Both | RECIST | Low | |
| ““ | ESR1 | 57/153 | 37.3% | 42/60 | 70.0% | No | Both | ““ | ||||
| B. O’Leary [5] | 2018 | dPCR | PIK3CA | 100/455 | 22.0% | 65/65 * | 100.0% | Yes | Endpoint | RECIST | Low | |
| ““ | ESR1 | 114/445 | 25.6% | 73/73 * | 100.0% | No | ““ | ““ | ||||
| J.S. Frenel [28] | 2015 | dPCR | PIK3CA | 1/7 | 14.3% | 1/7 | 14.3% | No | Endpoint | RECIST | Low | |
| ““ | TP53 | 5/7 | 71.4% | 2/7 | 28.6% | Yes | ““ | ““ | ||||
| S.J. Dawson [4] | 2013 | TAm-Seq | PIK3CA and/or TP53 | 24/52 | 46.2% | 25/30 | 83.3% | Yes | Continuous | RECIST | Low | |
| ““ | PIK3CA | 9/30 | 30.0% | 11/30 | 36.7% | n.d. | ||||||
| ““ | TP53 | 15/30 | 50.0% | 17/30 | 56.7% | n.d. | ||||||
| S. Hrebien [29] | 2019 | dPCR | PIK3CA, GATA3, ESR1 and/or TP53 | 38/58 | 78.1% | 35/35 * | 100.0% | Yes | Endpoint | n.a. | Low | |
| PIK3CA | 30/58 | 51.7% | 32/35 | 91.4% | n.d. | |||||||
| TP53 | 4/58 | 6.9% | 4/31 | 12.9% | n.d. | |||||||
| F. Ma + [14] | 2016 | NGS | PIK3CA, mTOR, PTEN and/or TP53 | 9/18 | 50.0% | 11/18 | 61.1% | Yes | Endpoint | RECIST | Low | |
| ““ | PIK3CA | 6/18 | 33.3% | 8/18 | 44.4% | n.d. | ||||||
| ““ | TP53 | 3/18 | 16.7% | 7/18 | 39.9% | n.d. | ||||||
| F. Ma [13] | 2019 | NGS | 193 gene panel | 37/37 | 100.0% | 21/21 | 100.0% | Yes | Endpoint | RECIST | Low | |
| ““ | PIK3CA | 13/37 | 35.1% | 10/21 | 47.6% | n.d. | ||||||
| ““ | TP53 | 20/37 | 54.1% | 13/21 | 61.9% | n.d. | ||||||
| S.W. Lok [30] | 2018 | dPCR | PIK3CA, ESR1, GATA3 and/or MAP3K1 | 28/33 | 84.8% | 28/33 | 84.8% | n.d. | Low | |||
| ““ | PIK3CA | 14/33 | 42.4% | 14/33 | 42.4% | n.d. | ||||||
| ““ | ESR1 | 10/33 | 30.3% | 10/33 | 30.3% | Yes | Both | RECIST | ||||
| ““ | GATA3 | 5/33 | 15.2% | 5/33 | 15.2% | n.d. | ||||||
| ““ | MAP3K1 | 4/33 | 12.1% | 4/33 | 12.1% | n.d. | ||||||
| C.X. Ma [31] | 2017 | NGS | HER2 | 9/381 | 2.4% | 11/11 * | 100.0% | Yes | Continuous | RECIST | Low | |
| ““ | PIK3CA | n.a. | 5/11 | 45.5% | n.d. | |||||||
| ““ | ESR1 | n.a. | 2/11 | 18.1% | n.d. | |||||||
| ““ | TP53 | n.a. | 6/11 | 54.5% | n.d. | |||||||
| C. Hufnagl [32] | 2020 | TAm-Seq | 8 gene panel | 4/4 | 100.0% | 4/4 | 100.0% | No | Continuous | RECIST, CA 15-3 | Moderate | |
| K. Page [33] | 2016 | dPCR | 16 gene panel | 21/42 | 50.0% | 9/9 * | 100.0% | Yes | Continuous | RECIST, CA 15-3 | Moderate | |
| ““ | PIK3CA | 12/42 | 28.6% | 6/9 | 66.7% | n.d. | ||||||
| ““ | ESR1 | 6/42 | 14.3% | 2/9 | 22.2% | n.d. | ||||||
| ““ | TP53 | 6/42 | 14.3% | 2/9 | 22.2% | n.d. | ||||||
| R.D. Baird [34] | 2019 | TAm-Seq | 20-gene panel | 12/30 | 40% | 4/4 * | 100% | Yes | Continuous | RECIST | Low | |
| ““ | PIK3CA | 7/30 | 23.3% | 2/4 | 50% | n.d. | ||||||
| ““ | ESR1 | 3/30 | 10% | 1/4 | 25% | n.d. | ||||||
| ““ | TP53 | 5/30 | 16.7% | 2/4 | 50% | n.d. | ||||||
| CNV | Guan [35] | 2020 | NGS | HER2 | 47/105 | 44.8% | 19/26 | 73.1% | Yes | Endpoint | Not defined | Low |
| B.S. Sorensen [36] | 2010 | qPCR | HER2 | 14/28 | 50.0% | 22/22 | 100.0% | Yes | Endpoint | Not defined | Low | |
| F. Ma + [14] | 2016 | NGS | HER2 | 13/17 | 76.5% | 13/17 | 76.5% | Yes | Continuous | RECIST | Low | |
| C. Suppan [6] | 2019 | FastSeq | Line1 | 10/29 | 34.5% | 29/29 | 100.0% | Yes | Continuous | CA 15-3 | Moderate | |
| Methylation | M.J. Fackler [7] | 2014 | qMSP | Cumulative gene index (10 genes) | 52/57 | 91.2% | 13/13 * | 100.0% | Yes | Continuous | RECIST | Low |
| 29/29 * | 100.0% | Yes | Endpoint | |||||||||
| K. Visvanathan [37] | 2016 | qMSP | Cumulative gene index (6/10 genes) | 129/129 | 100.0% | 129/129 | 100.0% | Yes | Endpoint | RECIST | Low | |
| M. Zurita [38] | 2010 | qMSP | 14-3-3-σ | 34/34 | 100.0% | 34/34 | 100.0% | Yes | Endpoint | RECIST | Low | |
| S. Kristiansen [39] | 2015 | qMSP | RASSF1A | n.a. | n.a. | 29/29 | 100.0% | Yes | Continuous | PTM | Moderate | |
| qMSP | LINE-1 | n.a. | n.a. | n.a | n.a | No | Continuous | PTM | ||||
| X.L. Liu [40] | 2020 | WGBS | Whole genome | 16/16 | 100.0% | 16/16 | 100.0% | Yes | Endpoint | Not defined | Moderate | |
| Size/Conc. | Z. Ye [41] | 2019 | qPCR | Alu115 and Alu81 | 117/117 | 100.0% | 22/22 | 100.0% | Yes | Endpoint | RECIST | Low |
| F. Clatot + [15] | 2020 | dPCR | cfDNA conc. | 103/103 | 100.0% | 70/70 | 100.0% | No | Continuous | RECIST | Low |
The column “Baseline” shows the number of patients in which the described aberration is present (nominator) relative to the group of patients in which the aberration is determined at baseline (denominator). The column “Longitudinal” shows the number of patients in which the described aberration is present at any time point (nominator) relative to the group of patients in which the aberration is measured longitudinally (denominator). * These studies monitored only baseline-positive samples longitudinally. + These studies monitored two types of biomarkers Abbreviations list: dPCR = digital PCR, NGS = next generation sequencing, Tam-Seq = tagged amplicon deep sequencing, FastSeq = fast aneuploidy screening test-sequencing system, qMSP = quantitative methylation specific PCR, WGBS = whole genome bisulfite sequencing, RECIST = response evaluation criteria in solid tumors, PTM = protein tumor marker, n.a. = not applicable, n.d. = not determined.