Clinicopathological and Prognostic Significance of Cancer Antigen 15-3 and Carcinoembryonic Antigen in Breast Cancer: A Meta-Analysis including 12,993 Patients
Table 2
Summary of the meta-analysis results.
Analysis
Univariate analysis
Multivariate analysis
N
HR (95% CI)
p
I2
Ph
N
HR (95% CI)
p
I2
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: values of Q test for heterogeneity test; OS: overall survival; DFS: disease-free survival; “—” means unavailable.
