J Clin Med Res

Journal of Clinical Medicine Research, ISSN 1918-3003 print, 1918-3011 online, Open Access

Article copyright, the authors; Journal compilation copyright, J Clin Med Res and Elmer Press Inc

Journal website https://jocmr.elmerjournals.com

Original Article

Volume 16, Number 10, October 2024, pages 491-502

The Effects of Preoperative Serum Carcinoembryonic Antigen, Cancer Antigen 15-3 and Cancer Antigen 125 on the Prognosis of Breast Cancer Patients With Different Molecular Subtypes

↓ Figure 1. Flow chart for determining the research object. CEA: carcinoembryonic antigen; CA15-3: cancer antigen 15-3; CA125: cancer antigen 125.

↓ Figure 2. The distribution and comparison of preoperative serum levels of CA125, CA15-3, and CEA in breast cancer patients in the elevated group and the normal group. The line on the bar is an error bar. *P < 0.001 indicates a significant difference. CEA: carcinoembryonic antigen; CA15-3: cancer antigen 15-3; CA125: cancer antigen 125.

↓ Figure 3. Kaplan-Meier survival curves of preoperative serum CEA, CA15-3, and CA125 in patients with luminal A subtype, luminal B subtype, HER2+ subtype, and TNBC. a, e, i: luminal A; b, f, j: luminal B; c, g, k: HER2+; d, h, l: TNBC. The red lines represent the elevated group, and the blue lines represent the normal group. CEA: carcinoembryonic antigen; CA15-3: cancer antigen 15-3; CA125: cancer antigen 125; HER2+: human epidermal growth factor receptor-2-enriched; TNBC: triple-negative breast cancer.

↓ Figure 4. Multivariate Cox regression analysis of the effects of preoperative serum CEA, CA15-3, and CA125 on survival of patients with different molecular subtypes of breast cancer. CEA: carcinoembryonic antigen; CA15-3: cancer antigen 15-3; CA125: cancer antigen 125; 95% CI: 95% confidence interval; HR: hazard ratio; HER2+: human epidermal growth factor receptor-2-enriched; TNBC: triple-negative breast cancer. *P < 0.05 versus normal group.

↓ **Table 1.** General Characteristics of the Study Population
Factor	N	%
CEA: carcinoembryonic antigen; CA15-3: cancer antigen 15-3; CA125: cancer antigen 125; HER2+: human epidermal growth factor receptor-2-enriched; TNBC: triple-negative breast cancer.
Age (years)
≤ 50	1,119	38.1
> 50	1,821	61.9
Median	52.5 (27.0 - 97.1)
Molecular subtype
Luminal A	448	15.2
Luminal B	1,695	57.7
HER2+	345	11.7
TNBC	452	15.4
Treatment
Chemotherapy	1,372	50.7
Endocrine treatment	881	32.6
Radiation treatment	453	16.7
Event
Alive	2,755	93.7
Dead	185	6.3
Tumor marker
CEA (µg/L)
Normal	2,642	89.9
Elevated	298	10.1
Median	1.68 (0.5 - 1,449.1)
CA15-3 (U/mL)
Normal	2,643	89.9
Elevated	297	10.1
Median	9.7 (2.3 - 800)
CA125 (U/mL)
Normal	2,600	88.4
Elevated	340	11.6
Median	13.8 (1.9 - 1,000)

↓ Table 1. General Characteristics of the Study Population

Factor

CEA: carcinoembryonic antigen; CA15-3: cancer antigen 15-3; CA125: cancer antigen 125; HER2+: human epidermal growth factor receptor-2-enriched; TNBC: triple-negative breast cancer.

Age (years)

≤ 50

1,119

38.1

> 50

1,821

61.9

Median

52.5 (27.0 - 97.1)

Molecular subtype

Luminal A

448

15.2

Luminal B

1,695

57.7

HER2+

345

11.7

TNBC

452

15.4

Treatment

Chemotherapy

1,372

50.7

Endocrine treatment

881

32.6

Radiation treatment

453

16.7

Event

Alive

2,755

93.7

Dead

185

6.3

Tumor marker

CEA (µg/L)

Normal

2,642

89.9

Elevated

298

10.1

Median

1.68 (0.5 - 1,449.1)

CA15-3 (U/mL)

Normal

2,643

89.9

Elevated

297

10.1

Median

9.7 (2.3 - 800)

CA125 (U/mL)

Normal

2,600

88.4

Elevated

340

11.6

Median

13.8 (1.9 - 1,000)

↓ **Table 2.** Correlation Between Preoperative Serum CEA, CA15-3, and CA125 Levels and Clinical Pathological Factors
Clinicopathologic factors	CEA	CA15-3	CA125
CEA: carcinoembryonic antigen; CA15-3: cancer antigen 15-3; CA125: cancer antigen 125; ER: estrogen receptor; HER2+: human epidermal growth factor receptor-2-enriched; PR: progesterone receptor; TNBC: triple-negative breast cancer.
Age (years)
≤ 50	71 (23.8%)	1,048 (39.7%)	< 0.001	118 (39.7%)	1,001 (37.9%)	0.574	175 (51.5%)	944 (36.3%)	< 0.001
> 50	227 (76.2%)	1,594 (60.3%)		179 (60.3%)	1,642 (62.1%)		165 (48.5%)	1,656 (63.7%)
Tumor size
T0-1	87 (29.2%)	1,348 (51.0%)	< 0.001	42 (14.2%)	1,393 (52.7%)	< 0.001	121 (35.6%)	1,314 (50.5%)	< 0.001
T2	128 (42.9%)	1,103 (41.7%)		148 (49.8%)	1,083 (41.0%)		149 (43.8%)	1,082 (41.6%)
T3-4	83 (27.9%)	191 (7.2%)		107 (36.0%)	167 (6.3%)		70 (20.6%)	204 (7.8%)
Lymph node status
N0	89 (29.9%)	1,488 (56.3%)	< 0.001	65 (21.9%)	1,512 (57.2%)	< 0.001	144 (42.4%)	1,433 (55.1%)	< 0.001
N1	90 (30.2%)	759 (28.7%)		101 (34.0%)	748 (28.3%)		96 (28.2%)	753 (29.0%)
N2-3	119 (39.9%)	395 (15.0%)		131 (44.1%)	383 (14.5%)		100 (29.4%)	414 (15.9%)
TNM stage
I	49 (16.4%)	1,003 (38.0%)	< 0.001	25 (8.4%)	1,027 (38.9%)	< 0.001	90 (26.5%)	962 (37.0%)	< 0.001
II	98 (32.9%)	1,159 (43.9%)		96 (32.3%)	1,161 (43.9%)		120 (35.3%)	1,137 (43.7%)
III	151 (50.7%)	480 (18.2%)		176 (59.3%)	455 (17.2%)		130 (38.2%)	501 (19.3%)
ER
Positive	198 (66.4%)	1,893 (71.7%)	0.070	213 (71.7%)	1,878 (71.1%)	0.864	198 (58.2%)	1,893 (72.8%)	< 0.001
Negative	100 (33.6%)	749 (28.3%)		84 (28.3%)	765 (28.9%)		142 (41.8%)	707 (27.2%)
PR
Positive	164 (55.0%)	1,720 (65.1%)	< 0.001	173 (58.2%)	1,711 (64.7%)	0.032	179 (52.6%)	1,705 (65.6%)	< 0.001
Negative	134 (45.0%)	922 (34.9%)		124 (41.8%)	932 (35.3%)		161 (47.4%)	895 (34.4%)
HER2
Positive	104 (34.9%)	567 (21.5%)	< 0.001	88 (29.6%)	583 (22.1%)	0.004	76 (22.4%)	595 (22.9%)	0.880
Negative	194 (65.1%)	2,075 (78.5%)		209 (70.4%)	2,060 (77.9%)		264 (77.6%)	2,005 (77.1%)
Molecular subtype
Luminal A	39 (13.1%)	409 (15.5%)	< 0.001	24 (8.1%)	424 (16.0%)	0.002	23 (6.8%)	425 (16.3%)	< 0.001
Luminal B	167 (56.0%)	1,528 (57.8%)		193 (65.0%)	1,502 (56.8%)		184 (54.1%)	1,511 (58.1%)
HER2+	58 (19.5%)	287 (10.9%)		32 (10.8%)	313 (11.8%)		40 (11.8%)	305 (11.7%)
TNBC	34 (11.4%)	418 (15.8%)		48 (16.2%)	404 (15.3%)		93 (27.4%)	359 (13.8%)
Histological grade
I	20 (6.7%)	415 (15.7%)	< 0.001	10 (3.4%)	425 (16.1%)	< 0.001	32 (9.4%)	403 (15.5%)	< 0.001
II	111 (37.2%)	1,285 (48.6%)		95 (32.0%)	1,301 (49.2%)		129 (37.9%)	1,267 (48.7%)
III	109 (36.6%)	490 (18.5%)		131 (44.1%)	468 (17.7%)		116 (34.1%)	483 (18.6%)
Unknown	58 (19.5%)	452 (17.1%)		61 (20.5%)	449 (17.0%)		63 (18.5%)	447 (17.2%)
Chemotherapy
Done	82 (27.5%)	1,290 (48.8%)	< 0.001	88 (29.6%)	1,284 (48.6%)	< 0.001	138 (40.6%)	1,234 (47.5%)	0.020
No	216 (72.5%)	1,352 (51.2%)		209 (70.4%)	1,359 (51.4%)		202 (59.4%)	1,366 (52.5%)
Radiotherapy
Done	28 (9.4%)	425 (16.1%)	0.003	29 (9.8%)	424 (16.0%)	0.005	48 (14.1%)	405 (15.6%)	0.535
No	270 (90.6%)	2,217 (83.9%)		268 (90.2%)	2,219 (84.0%)		292 (85.9%)	2,195 (84.4%)
Endocrine treatment
Done	57 (19.1%)	824 (31.2%)	< 0.001	62 (20.9%)	819 (31.0%)	< 0.001	87 (25.6%)	794 (30.5%)	0.070
No	241 (80.9%)	1,818 (68.8%)		235 (79.1%)	1,824 (69.0%)		253 (74.4%)	1,806 (69.5%)

↓ Table 2. Correlation Between Preoperative Serum CEA, CA15-3, and CA125 Levels and Clinical Pathological Factors

Clinicopathologic factors

CEA

CA15-3

CA125

Elevated (N = 298)

Normal (N = 2,642)

P value

Elevated (N = 297)

Normal (N = 2,643)

P value

Elevated (N = 340)

Normal (N = 2,600)

P value

CEA: carcinoembryonic antigen; CA15-3: cancer antigen 15-3; CA125: cancer antigen 125; ER: estrogen receptor; HER2+: human epidermal growth factor receptor-2-enriched; PR: progesterone receptor; TNBC: triple-negative breast cancer.

Age (years)

≤ 50

71 (23.8%)

1,048 (39.7%)

< 0.001

118 (39.7%)

1,001 (37.9%)

0.574

175 (51.5%)

944 (36.3%)

< 0.001

> 50

227 (76.2%)

1,594 (60.3%)

179 (60.3%)

1,642 (62.1%)

165 (48.5%)

1,656 (63.7%)

Tumor size

T0-1

87 (29.2%)

1,348 (51.0%)

< 0.001

42 (14.2%)

1,393 (52.7%)

< 0.001

121 (35.6%)

1,314 (50.5%)

< 0.001

128 (42.9%)

1,103 (41.7%)

148 (49.8%)

1,083 (41.0%)

149 (43.8%)

1,082 (41.6%)

T3-4

83 (27.9%)

191 (7.2%)

107 (36.0%)

167 (6.3%)

70 (20.6%)

204 (7.8%)

Lymph node status

89 (29.9%)

1,488 (56.3%)

< 0.001

65 (21.9%)

1,512 (57.2%)

< 0.001

144 (42.4%)

1,433 (55.1%)

< 0.001

90 (30.2%)

759 (28.7%)

101 (34.0%)

748 (28.3%)

96 (28.2%)

753 (29.0%)

N2-3

119 (39.9%)

395 (15.0%)

131 (44.1%)

383 (14.5%)

100 (29.4%)

414 (15.9%)

TNM stage

49 (16.4%)

1,003 (38.0%)

< 0.001

25 (8.4%)

1,027 (38.9%)

< 0.001

90 (26.5%)

962 (37.0%)

< 0.001

98 (32.9%)

1,159 (43.9%)

96 (32.3%)

1,161 (43.9%)

120 (35.3%)

1,137 (43.7%)

III

151 (50.7%)

480 (18.2%)

176 (59.3%)

455 (17.2%)

130 (38.2%)

501 (19.3%)

Positive

198 (66.4%)

1,893 (71.7%)

0.070

213 (71.7%)

1,878 (71.1%)

0.864

198 (58.2%)

1,893 (72.8%)

< 0.001

Negative

100 (33.6%)

749 (28.3%)

84 (28.3%)

765 (28.9%)

142 (41.8%)

707 (27.2%)

Positive

164 (55.0%)

1,720 (65.1%)

< 0.001

173 (58.2%)

1,711 (64.7%)

0.032

179 (52.6%)

1,705 (65.6%)

< 0.001

Negative

134 (45.0%)

922 (34.9%)

124 (41.8%)

932 (35.3%)

161 (47.4%)

895 (34.4%)

HER2

Positive

104 (34.9%)

567 (21.5%)

< 0.001

88 (29.6%)

583 (22.1%)

0.004

76 (22.4%)

595 (22.9%)

0.880

Negative

194 (65.1%)

2,075 (78.5%)

209 (70.4%)

2,060 (77.9%)

264 (77.6%)

2,005 (77.1%)

Molecular subtype

Luminal A

39 (13.1%)

409 (15.5%)

< 0.001

24 (8.1%)

424 (16.0%)

0.002

23 (6.8%)

425 (16.3%)

< 0.001

Luminal B

167 (56.0%)

1,528 (57.8%)

193 (65.0%)

1,502 (56.8%)

184 (54.1%)

1,511 (58.1%)

HER2+

58 (19.5%)

287 (10.9%)

32 (10.8%)

313 (11.8%)

40 (11.8%)

305 (11.7%)

TNBC

34 (11.4%)

418 (15.8%)

48 (16.2%)

404 (15.3%)

93 (27.4%)

359 (13.8%)

Histological grade

20 (6.7%)

415 (15.7%)

< 0.001

10 (3.4%)

425 (16.1%)

< 0.001

32 (9.4%)

403 (15.5%)

< 0.001

111 (37.2%)

1,285 (48.6%)

95 (32.0%)

1,301 (49.2%)

129 (37.9%)

1,267 (48.7%)

III

109 (36.6%)

490 (18.5%)

131 (44.1%)

468 (17.7%)

116 (34.1%)

483 (18.6%)

Unknown

58 (19.5%)

452 (17.1%)

61 (20.5%)

449 (17.0%)

63 (18.5%)

447 (17.2%)

Chemotherapy

Done

82 (27.5%)

1,290 (48.8%)

< 0.001

88 (29.6%)

1,284 (48.6%)

< 0.001

138 (40.6%)

1,234 (47.5%)

0.020

216 (72.5%)

1,352 (51.2%)

209 (70.4%)

1,359 (51.4%)

202 (59.4%)

1,366 (52.5%)

Radiotherapy

Done

28 (9.4%)

425 (16.1%)

0.003

29 (9.8%)

424 (16.0%)

0.005

48 (14.1%)

405 (15.6%)

0.535

270 (90.6%)

2,217 (83.9%)

268 (90.2%)

2,219 (84.0%)

292 (85.9%)

2,195 (84.4%)

Endocrine treatment

Done

57 (19.1%)

824 (31.2%)

< 0.001

62 (20.9%)

819 (31.0%)

< 0.001

87 (25.6%)

794 (30.5%)

0.070

241 (80.9%)

1,818 (68.8%)

235 (79.1%)

1,824 (69.0%)

253 (74.4%)

1,806 (69.5%)

↓ Table 3. Univariate Cox Regression Analysis of Preoperative Serum CEA, CA15-3, and CA125 and Overall Survival of Breast Cancer

Tumor marker

95.0% CI

P value

Lower

Upper

CEA: carcinoembryonic antigen; CA15-3: cancer antigen 15-3; CA125: cancer antigen 125; CI: confidence interval; HER2+: human epidermal growth factor receptor-2-enriched; HR: hazard ratio; TNBC: triple-negative breast cancer.

Total patients

CEA

Normal

1.00

Elevated

5.943

4.407

8.015

< 0.001

CA15-3

Normal

1.00

Elevated

6.845

5.099

9.190

< 0.001

CA125

Normal

1.00

Elevated

3.466

2.524

4.759

< 0.001

Subtype

Luminal A

CEA

Normal

1.00

Elevated

17.32

6.158

48.69

< 0.001

CA15-3

Normal

1.00

Elevated

24.45

8.669

68.93

< 0.001

CA125

Normal

1.00

Elevated

3.673

0.828

16.29

0.087

Luminal B

CEA

Normal

1.00

Elevated

6.432

4.114

10.06

< 0.001

CA15-3

Normal

1.00

Elevated

7.901

5.113

12.21

< 0.001

CA125

Normal

1.00

Elevated

3.631

2.241

5.883

< 0.001

HER2+

CEA

Normal

1.00

Elevated

4.693

2.330

9.453

CA15-3

Normal

1.00

Elevated

8.417

3.969

17.85

CA125

Normal

1.00

Elevated

2.235

0.919

5.436

0.076

CEA

Normal

1.00

Elevated

4.426

2.416

8.107

< 0.001

TNBC

CA15-3

Normal

1.00

Elevated

3.629

2.031

6.483

< 0.001

CA125

Normal

1.00

Elevated

2.571

1.509

4.381

< 0.001

↓ **Table 4.** Multivariate Cox Regression Analysis of the Association Between Preoperative Serum CEA, CA15-3, and CA125 and Traditional Clinicopathologic Factors and Overall Survival of Breast Cancer Patients
Breast cancer subtypes	HR	95% CI	P value
CEA: carcinoembryonic antigen; CA15-3: cancer antigen 15-3; CA125: cancer antigen 125; CI: confidence interval; HER2+: human epidermal growth factor receptor-2-enriched; HR: hazard ratio; TNBC: triple-negative breast cancer.
Total patients
Tumor marker
CEA elevated vs. CEA normal	2.097	1.479 - 2.973	< 0.001
CA15-3 elevated vs. CA15-3 normal	1.749	1.197 - 2.556	0.004
Tumor size
T2 vs. T0-1	2.070	1.179 - 3.635	0.011
T3-4 vs. T0-1	2.889	1.558 - 5.357	< 0.001
Nodal status
N2 vs. N1	1.771	1.066 - 2.943	0.027
Chemotherapy
Done vs. no	0.421	0.277 - 0.641	< 0.001
Endocrine
Done vs. no	0.456	0.237 - 0.875	0.018
Luminal A
Tumor marker
CEA elevated vs. CEA normal	6.475	1.850 - 22.66	0.003
CA15-3 elevated vs. CA15-3 normal	5.192	1.153 - 23.38	0.032
CA125 elevated vs. CA125 normal	7.294	1.152 - 46.18	0.035
Luminal B
Tumor size
T3-4 vs. T0-1	3.103	1.235 - 7.797	0.016
Chemotherapy
Done vs. no	0.398	0.211 - 0.749	0.004
HER2+
Tumor marker
CA15-3 elevated vs. CA15-3 normal	3.155	1.325 - 7.509	0.009
TNBC
Tumor marker
CEA elevated vs. CEA normal	2.390	1.247 - 4.583	0.009
Chemotherapy
Done vs. no	0.385	0.188 - 0.786	0.009

↓ Table 4. Multivariate Cox Regression Analysis of the Association Between Preoperative Serum CEA, CA15-3, and CA125 and Traditional Clinicopathologic Factors and Overall Survival of Breast Cancer Patients

Breast cancer subtypes

95% CI

P value

Total patients

Tumor marker

CEA elevated vs. CEA normal

2.097

1.479 - 2.973

< 0.001

CA15-3 elevated vs. CA15-3 normal

1.749

1.197 - 2.556

0.004

Tumor size

T2 vs. T0-1

2.070

1.179 - 3.635

0.011

T3-4 vs. T0-1

2.889

1.558 - 5.357

< 0.001

Nodal status

N2 vs. N1

1.771

1.066 - 2.943

0.027

Chemotherapy

Done vs. no

0.421

0.277 - 0.641

< 0.001

Endocrine

Done vs. no

0.456

0.237 - 0.875

0.018

Luminal A

Tumor marker

CEA elevated vs. CEA normal

6.475

1.850 - 22.66

0.003

CA15-3 elevated vs. CA15-3 normal

5.192

1.153 - 23.38

0.032

CA125 elevated vs. CA125 normal

7.294

1.152 - 46.18

0.035

Luminal B

Tumor size

T3-4 vs. T0-1

3.103

1.235 - 7.797

0.016

Chemotherapy

Done vs. no

0.398

0.211 - 0.749

0.004

HER2+

Tumor marker

CA15-3 elevated vs. CA15-3 normal

3.155

1.325 - 7.509

0.009

TNBC

Tumor marker

CEA elevated vs. CEA normal

2.390

1.247 - 4.583

0.009

Chemotherapy

Done vs. no

0.385

0.188 - 0.786

0.009