Table 2.
Summary of the meta-analysis results.
| Analysis | Univariate analysis | Multivariate analysis | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| N | HR (95% CI) | p | I 2 | Ph | N | HR (95% CI) | p | I 2 | Ph | |
| CA15-3 DFS | ||||||||||
| All | 14 | 2.61 (2.17–3.13) | <0.001 | 50 | 0.02 | 10 | 1.56 (1.38–1.76) | <0.001 | 31 | 0.16 |
| Subgroup 1 | ||||||||||
| Primary early-stage breast cancer | 9 | 2.57 (2.14–3.08) | <0.001 | 21 | 0.25 | 7 | 1.80 (1.53–2.11) | <0.001 | 0 | 0.63 |
| Metastatic breast cancer | 2 | 2.00 (1.46–2.74) | <0.001 | 0 | 0.69 | 1 | 1.28 (0.43–3.80) | 0.65 | — | — |
| Primary all-stage or unclear-stage breast cancer | 3 | 2.88 (1.54–5.41) | <0.001 | 82 | 0.004 | 2 | 1.28 (1.06–1.55) | <0.001 | 40 | 0.20 |
| Subgroup 2 | ||||||||||
| Cut-off ≤ 25 | 6 | 2.84 (2.30–3.50) | <0.001 | 0 | 0.77 | 5 | 1.80 (1.50–2.16) | <0.001 | 0 | 0.85 |
| Cut-off > 25 | 6 | 2.69 (1.87–3.87) | <0.001 | 75 | 0.001 | 4 | 1.39 (1.17–1.64) | <0.001 | 59 | 0.06 |
| Subgroup 3 | ||||||||||
| Asia and Africa | 8 | 3.18 (2.46–4.11) | <0.001 | 44 | 0.08 | 6 | 1.96 (1.57–2.44) | <0.001 | 0 | 0.65 |
| Europe and America | 6 | 2.14 (1.82–2.52) | <0.001 | 0 | 0.67 | 4 | 1.41 (1.22–1.63) | <0.001 | 24 | 0.27 |
| Subgroup 4 | ||||||||||
| Sample size < 500 | 11 | 2.37 (2.00–2.81) | <0.001 | 20 | 0.26 | 7 | 1.78 (1.50–2.10) | <0.001 | 0 | 0.65 |
| Sample size ≥ 500 | 3 | 3.36 (2.01–5.61) | <0.001 | 79 | 0.008 | 3 | 1.35 (1.13–1.61) | 0.001 | 50 | 0.14 |
| Subgroup 5 | ||||||||||
| Publish year > 2010 | 7 | 2.82 (2.3–3.48) | <0.001 | 0 | 0.45 | 6 | 1.80 (1.50–2.17) | <0.001 | 0 | 0.53 |
| Publish year ≤ 2010 | 7 | 2.45 (1.86–3.23) | <0.001 | 69 | 0.004 | 4 | 1.39 (1.19–1.64) | <0.001 | 39 | 0.18 |
| CA15-3 OS | ||||||||||
| All | 21 | 2.86 (2.31–3.54) | <0.001 | 72 | <0.0001 | 15 | 2.03 (1.76–2.33) | <0.001 | 0 | 0.45 |
| Subgroup 1 | ||||||||||
| Primary early-stage breast cancer | 7 | 2.95 (2.28–3.82) | <0.001 | 22 | 0.26 | 6 | 1.93 (1.46–2.55) | <0.001 | 0 | 0.84 |
| Metastatic breast cancer | 6 | 1.79 (1.51–2.12) | <0.001 | 0 | 0.66 | 3 | 1.85 (1.47–2.32) | <0.001 | 0 | 0.78 |
| Primary all-stage or unclear-stage breast cancer | 8 | 3.87 (2.74–5.46) | <0.001 | 74 | <0.0001 | 6 | 2.31 (1.83–2.93) | <0.001 | 47 | 0.09 |
| Subgroup 2 | ||||||||||
| Cut-off ≤ 25 | 5 | 3.11 (2.39–4.05) | <0.001 | 0 | 0.59 | 5 | 1.98 (1.46–2.69) | <0.001 | 0 | 0.90 |
| Cut-off > 25 | 10 | 3.57 (2.62–4.88) | <0.001 | 74 | <0.0001 | 7 | 2.24 (1.79–2.80) | <0.001 | 46 | 0.09 |
| Subgroup 3 | ||||||||||
| Asia and Africa | 11 | 3.50 (2.59–4.71) | <0.001 | 70 | 0.0002 | 8 | 1.93 (1.58–2.35) | <0.001 | 34 | 0.16 |
| Europe and America | 10 | 2.35 (1.74–3.18) | <0.001 | 72 | 0.0002 | 7 | 2.13 (1.74–2.60) | <0.001 | 0 | 0.81 |
| Subgroup 4 | ||||||||||
| Sample size < 500 | 18 | 2.87 (2.24–3.7) | <0.001 | 75 | <0.0001 | 12 | 2.03 (1.74–2.38) | <0.001 | 21 | 0.23 |
| Sample size ≥ 500 | 3 | 2.72 (1.96–3.78) | <0.001 | 37 | 0.20 | 3 | 1.99 (1.43–2.77) | <0.001 | 0 | 0.99 |
| Subgroup 5 | ||||||||||
| Publish year > 2010 | 10 | 3.17 (2.33–4.31) | <0.001 | 62 | 0.005 | 8 | 1.82 (1.52–2.18) | <0.001 | 0 | 0.90 |
| Publish year ≤ 2010 | 11 | 2.65 (1.94–3.62) | <0.001 | 79 | <0.0001 | 7 | 2.41 (1.92–3.03) | <0.001 | 21 | 0.27 |
| CEA DFS | ||||||||||
| All | 10 | 2.60 (2.23–3.04) | <0.001 | 0 | 0.91 | 9 | 1.77 (1.53–2.04) | <0.001 | 0 | 0.82 |
| Subgroup 1 | ||||||||||
| Primary early-stage breast cancer | 6 | 2.80 (2.24–3.52) | <0.001 | 0 | 0.48 | 5 | 1.94 (1.56–2.40) | <0.001 | 0 | 0.72 |
| Metastatic breast cancer | 1 | 2.31 (1.26–4.24) | 0.007 | — | — | 2 | 1.91 (1.22–3.00) | 0.005 | 0 | 0.71 |
| Primary all-stage or unclear-stage breast cancer | 3 | 2.45 (1.94–3.09) | <0.001 | 0 | 0.80 | 2 | 1.58 (1.28–1.96) | <0.001 | 0 | 0.56 |
| Subgroup 2 | ||||||||||
| Cut-off ≤ 5 | 6 | 2.77 (2.29–3.37) | <0.001 | 0 | 0.48 | 6 | 1.74 (1.49–2.04) | <0.001 | 0 | 0.54 |
| Cut-off > 5 | 3 | 2.31 (1.72–3.10) | <0.001 | 0 | 0.98 | 1 | 1.84 (1.07–3.16) | <0.001 | — | — |
| Subgroup 3 | ||||||||||
| Asia and Africa | 6 | 2.65 (2.19–3.20) | <0.001 | 0 | 0.46 | 5 | 1.95 (1.53–2.48) | <0.001 | 0 | 0.89 |
| Europe and America | 4 | 2.50 (1.89–3.32) | <0.001 | 0 | 0.80 | 4 | 1.67 (1.40–2.00) | <0.001 | 0 | 0.52 |
| Subgroup 4 | ||||||||||
| Sample size < 500 | 6 | 2.62 (2.11–3.24) | <0.001 | 0 | 0.54 | 7 | 1.87 (1.54–2.26) | <0.001 | 0 | 0.97 |
| Sample size ≥ 500 | 4 | 2.59 (2.06–3.25) | <0.001 | 0 | 0.64 | 2 | 1.65 (1.33–2.05) | <0.001 | 59 | 0.12 |
| Subgroup 5 | ||||||||||
| Publish year > 2010 | 5 | 2.79 (2.15–3.60) | <0.001 | 0 | 0.50 | 7 | 1.87 (1.54–2.26) | <0.001 | 0 | 0.97 |
| Publish year ≤ 2010 | 5 | 2.50 (2.05–3.04) | <0.001 | 0 | 0.74 | 2 | 1.65 (1.33–2.05) | <0.001 | 59 | 0.12 |
| CEA OS | ||||||||||
| All | 16 | 2.46 (1.93–3.15) | <0.001 | 70 | <0.0001 | 8 | 1.72 (1.49–1.99) | <0.001 | 0 | 0.69 |
| Subgroup 1 | ||||||||||
| Primary early-stage breast cancer | 7 | 3.68 (2.65–5.09) | <0.001 | 33 | 0.17 | 4 | 1.95 (1.49–2.57) | <0.001 | 0 | 0.89 |
| Metastatic breast cancer | 4 | 1.52 (1.27–1.82) | <0.001 | 0 | 0.41 | 1 | 1.37 (1.02–1.85) | 0.04 | — | — |
| Primary all-stage or unclear-stage breast cancer | 5 | 2.61 (1.88–3.62) | <0.001 | 42 | 0.14 | 3 | 1.79 (1.46–2.20) | <0.001 | 0 | 0.64 |
| Subgroup 2 | ||||||||||
| Cut-off ≤ 5 | 8 | 3.80 (2.67–5.39) | <0.001 | 59 | 0.02 | 6 | 1.86 (1.56–2.20) | <0.001 | 0 | 0.88 |
| Cut-off > 5 | 4 | 2.34 (1.73–3.17) | <0.001 | 0 | 0.96 | 1 | 1.77 (1.03–3.03) | <0.001 | — | — |
| Subgroup 3 | ||||||||||
| Asia and Africa | 11 | 2.82 (2.07–3.85) | <0.001 | 72 | <0.001 | 7 | 1.65 (1.38–1.96) | <0.001 | 0 | 0.70 |
| Europe and America | 5 | 1.87 (1.26–2.77) | 0.002 | 61 | 0.04 | 1 | 1.91 (1.48–2.46) | <0.001 | — | — |
| Subgroup 4 | ||||||||||
| Sample size < 500 | 13 | 2.48 (1.84–3.34) | <0.001 | 75 | <0.0001 | 6 | 1.64 (1.37–1.95) | <0.001 | 0 | 0.60 |
| Sample size ≥ 500 | 3 | 2.29 (1.75–3.00) | <0.001 | 0 | 0.48 | 2 | 1.91 (1.50–2.45) | <0.001 | 0 | 0.96 |
| Subgroup 5 | ||||||||||
| Publish year > 2010 | 9 | 3.27 (2.22–4.82) | <0.001 | 73 | <0.0001 | 6 | 1.64 (1.37–1.95) | <0.001 | 0 | 0.60 |
| Publish year ≤ 2010 | 7 | 1.82 (1.39–2.39) | <0.001 | 53 | 0.05 | 2 | 1.91 (1.50–2.45) | <0.001 | 0 | 0.96 |
N: number of studies; HR: hazard ratio; 95% CI: 95% confidence interval; Ph: p values of Q test for heterogeneity test; OS: overall survival; DFS: disease-free survival; “—” means unavailable.