World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://wjon.elmerpub.com

Original Article

Volume 17, Number 1, February 2026, pages 52-62

Organ-Specific Clinicopathological Features That Are Associated With Post-Relapse Survival of Metastatic Breast Cancer in Japanese Women: A Multicenter Cohort Study

Figure 1. Flow diagram of study design. A flow diagram of the study design, including inclusion and exclusion criteria, is shown. MBC: metastatic breast cancer.

Figure 2. Kaplan-Meier curves for post-relapse survival according to organs of initial distant recurrence. The curves, stratified by the organs of initial distant recurrence, represent survival outcomes observed over a median follow-up period of 62.9 months (95% CI: 57.4 - 69.9). The blue, red, purple, and black curves correspond to brain-only, lung-only, liver-only, and bone-only groups, respectively. PRS: post-relapse survival; CI: confidence interval.

Figure 3. Systemic and local treatment patterns after distant recurrence according to the site of initial metastasis. (a) Number of treatment regimens for MBC according to organs of initial distant recurrence are shown and stratified by the box plots. (b) Details of local treatment for organs of initial distant recurrence. (c) Details of radiation therapy for brain metastasis.

Figure 4. Kaplan-Meier curves of post-relapse survival by molecular subtype in each metastatic site. Kaplan-Meier curves of PRS according to molecular subtype in the (a) brain-only, (b) lung-only, (c) liver-only, and (d) bone-only groups are shown. The blue, red, purple, and black curves correspond to patients with luminal, luminal-HER2, HER2-enriched, and triple-negative MBC, respectively. Dots on each curve indicate censored cases. PRS: post-relapse survival; CI: confidence interval; N.R: not reached; N.E: not estimable; MBC: metastatic breast cancer; HER2: human epidermal growth factor receptor 2.

**Table 1.** Patients’ Clinical and Pathological Background at Baseline
Baseline factors	All (n = 309)	Brain-only (n = 49)	Lung-only (n = 91)	Liver-only (n = 64)	Bone-only (n = 105)	P value
PBC: primary breast cancer; MBC: metastatic breast cancer; HER2: human epidermal growth factor receptor 2; DMFS, distant metastasis free survival.
Age at PBC diagnosis (years), median (range)	58 (21 - 89)	58 (27 - 84)	59 (21 - 89)	56 (30 - 86)	58 (31 - 77)	0.575
Age at MBC diagnosis (years), median (range)	61 (29 - 90)	59 (29 - 84)	62 (29 - 90)	59 (34 - 87)	61 (35 - 81)	0.728
Histological type
Invasive ductal carcinoma	266 (86%)	45 (92%)	76 (84%)	58 (91%)	87 (83%)	0.276
Others	43 (14%)	4 (8%)	15 (16%)	6 (9%)	18 (17%)
Clinical disease stage of PBC
Stage I	54 (17%)	4 (8%)	16 (18%)	13 (20%)	21 (20%)	0.288
Stage II/III	255 (83%)	45 (92%)	75 (82%)	51 (80%)	84 (80%)
Pathological disease stage of PBC
Stage 0/I	67 (21%)	20 (40%)	19 (21%)	11 (17%)	17 (16%)	0.004
Stage II/III	242 (78%)	29 (60%)	72 (79%)	53 (83%)	88 (84%)
Nuclear grade
Grade 1/2	141 (65%)	11 (48%)	33 (53%)	30 (59%)	67 (83%)	< 0.001
Grade 3	76 (35%)	12 (52%)	29 (47%)	21 (41%)	14 (17%)
Unknown	92	26	29	13	24
Ki67 labeling index
Low (≤ 20%)	62 (27%)	8 (24%)	9 (12%)	20 (41%)	25 (35%)	0.002
High (> 20%)	165 (73%)	26 (76%)	64 (88%)	29 (59%)	46 (65%)
Unknown	82	15	18	15	34
Molecular subtypes
Luminal	181 (59%)	14 (29%)	47 (52%)	39 (61%)	81 (77%)	< 0.001
Luminal-HER2	32 (10%)	7 (14%)	7 (8%)	11 (17%)	7 (7%)
HER2-enriched	30 (10%)	13 (27%)	11 (12%)	3 (5%)	3 (3%)
Triple-negative	66 (21%)	15 (31%)	26 (29%)	11 (17%)	14 (13%)
Adjuvant chemotherapy for PBC
Yes	219 (71%)	42 (86%)	55 (60%)	46 (72%)	76 (72%)	0.017
Neoadjuvant	143	32	37	34	40
Adjuvant	76	10	18	12	36
No	90 (29%)	7 (14%)	36 (40%)	18 (28%)	29 (28%)
DMFS (months), median (range)	29.4 (1 - 198)	13.5 (1 - 198)	34.4 (1 - 172)	26.1 (2 - 134)	37.0 (2 - 167)	0.004
Primary trigger for MBC diagnosis
Subjective symptoms	123 (42%)	44 (96%)	13 (15%)	14 (23%)	52 (51%)	< 0.001
Regular surveillance	172 (58%)	2 (4%)	75 (85%)	46 (77%)	49 (49%)
Unknown	14	3	3	4	4

Table 1. Patients’ Clinical and Pathological Background at Baseline

Baseline factors

All (n = 309)

Brain-only (n = 49)

Lung-only (n = 91)

Liver-only (n = 64)

Bone-only (n = 105)

P value

PBC: primary breast cancer; MBC: metastatic breast cancer; HER2: human epidermal growth factor receptor 2; DMFS, distant metastasis free survival.

Age at PBC diagnosis (years), median (range)

58 (21 - 89)

58 (27 - 84)

59 (21 - 89)

56 (30 - 86)

58 (31 - 77)

0.575

Age at MBC diagnosis (years), median (range)

61 (29 - 90)

59 (29 - 84)

62 (29 - 90)

59 (34 - 87)

61 (35 - 81)

0.728

Histological type

Invasive ductal carcinoma

266 (86%)

45 (92%)

76 (84%)

58 (91%)

87 (83%)

0.276

Others

43 (14%)

4 (8%)

15 (16%)

6 (9%)

18 (17%)

Clinical disease stage of PBC

Stage I

54 (17%)

4 (8%)

16 (18%)

13 (20%)

21 (20%)

0.288

Stage II/III

255 (83%)

45 (92%)

75 (82%)

51 (80%)

84 (80%)

Pathological disease stage of PBC

Stage 0/I

67 (21%)

20 (40%)

19 (21%)

11 (17%)

17 (16%)

0.004

Stage II/III

242 (78%)

29 (60%)

72 (79%)

53 (83%)

88 (84%)

Nuclear grade

Grade 1/2

141 (65%)

11 (48%)

33 (53%)

30 (59%)

67 (83%)

< 0.001

Grade 3

76 (35%)

12 (52%)

29 (47%)

21 (41%)

14 (17%)

Unknown

Ki67 labeling index

Low (≤ 20%)

62 (27%)

8 (24%)

9 (12%)

20 (41%)

25 (35%)

0.002

High (> 20%)

165 (73%)

26 (76%)

64 (88%)

29 (59%)

46 (65%)

Unknown

Molecular subtypes

Luminal

181 (59%)

14 (29%)

47 (52%)

39 (61%)

81 (77%)

< 0.001

Luminal-HER2

32 (10%)

7 (14%)

7 (8%)

11 (17%)

7 (7%)

HER2-enriched

30 (10%)

13 (27%)

11 (12%)

3 (5%)

3 (3%)

Triple-negative

66 (21%)

15 (31%)

26 (29%)

11 (17%)

14 (13%)

Adjuvant chemotherapy for PBC

Yes

219 (71%)

42 (86%)

55 (60%)

46 (72%)

76 (72%)

0.017

Neoadjuvant

143

Adjuvant

90 (29%)

7 (14%)

36 (40%)

18 (28%)

29 (28%)

DMFS (months), median (range)

29.4 (1 - 198)

13.5 (1 - 198)

34.4 (1 - 172)

26.1 (2 - 134)

37.0 (2 - 167)

0.004

Primary trigger for MBC diagnosis

Subjective symptoms

123 (42%)

44 (96%)

13 (15%)

14 (23%)

52 (51%)

< 0.001

Regular surveillance

172 (58%)

2 (4%)

75 (85%)

46 (77%)

49 (49%)

Unknown

**Table 2.** Factors Relating With Post-Relapse Survival (N = 309)
Clinicopathological factors	N	Univariate analysis	Multivariable analysis
HR: hazard ratio; 95% CI: 95% confidence interval; MBC: metastatic breast cancer; HER2: human epidermal growth factor receptor 2.
Age at MBC diagnosis	309	1.01	1.00 - 1.03	0.020	1.03	1.01 - 1.04	< 0.001
Menopausal status at MBC diagnosis
Premenopausal	78	Reference
Postmenopausal	231	1.07	0.75 - 1.52	0.719
Histological type
Invasive ductal carcinoma	266	Reference
Others	43	1.29	0.86 - 1.94	0.213
Nuclear grade
Grade 1/2	141	Reference
Grade 3	76	2.27	1.56 - 3.31	< 0.001
Ki67 labeling index
Low (≤ 20%)	62	Reference			Reference
High (> 20%)	165	1.28	0.86 - 1.92	0.224	1.35	0.86 - 2.11	0.189
Molecular subtypes
Luminal	181	Reference			Reference
Luminal-HER2	32	1.44	0.89 - 2.32	0.134	1.36	0.72 - 2.58	0.349
HER2-enriched	30	1.18	0.69 - 2.01	0.545	0.74	0.37 - 1.49	0.398
Triple-negative	66	2.82	2.00 - 3.97	< 0.001	3.05	1.96 - 4.74	< 0.001
Organs of initial distant recurrence
Bones	105	Reference			Reference
Lungs	91	1.07	0.72 - 1.60	0.741	1.55	0.90 - 2.66	0.111
Liver	64	1.86	1.23 - 2.81	0.003	2.78	1.54 - 5.03	< 0.001
Brain	49	3.48	2.29 - 5.29	< 0.001	2.89	1.60 - 5.22	< 0.001
Primary trigger for MBC diagnosis
Regular surveillance	172	Reference			Reference
Subjective symptoms	123	2.17	1.59 - 2.95	< 0.001	2.13	1.30 - 3.51	0.003

Table 2. Factors Relating With Post-Relapse Survival (N = 309)

Clinicopathological factors

Univariate analysis

Multivariable analysis

95% CI

P value

95% CI

P value

HR: hazard ratio; 95% CI: 95% confidence interval; MBC: metastatic breast cancer; HER2: human epidermal growth factor receptor 2.

Age at MBC diagnosis

309

1.01

1.00 - 1.03

0.020

1.03

1.01 - 1.04

< 0.001

Menopausal status at MBC diagnosis

Premenopausal

Reference

Postmenopausal

231

1.07

0.75 - 1.52

0.719

Histological type

Invasive ductal carcinoma

266

Reference

Others

1.29

0.86 - 1.94

0.213

Nuclear grade

Grade 1/2

141

Reference

Grade 3

2.27

1.56 - 3.31

< 0.001

Ki67 labeling index

Low (≤ 20%)

Reference

High (> 20%)

165

1.28

0.86 - 1.92

0.224

1.35

0.86 - 2.11

0.189

Molecular subtypes

Luminal

181

Reference

Luminal-HER2

1.44

0.89 - 2.32

0.134

1.36

0.72 - 2.58

0.349

HER2-enriched

1.18

0.69 - 2.01

0.545

0.74

0.37 - 1.49

0.398

Triple-negative

2.82

2.00 - 3.97

< 0.001

3.05

1.96 - 4.74

< 0.001

Organs of initial distant recurrence

Bones

105

Reference

Lungs

1.07

0.72 - 1.60

0.741

1.55

0.90 - 2.66

0.111

Liver

1.86

1.23 - 2.81

0.003

2.78

1.54 - 5.03

< 0.001

Brain

3.48

2.29 - 5.29

< 0.001

2.89

1.60 - 5.22

< 0.001

Primary trigger for MBC diagnosis

Regular surveillance

172

Reference

Subjective symptoms

123

2.17

1.59 - 2.95

< 0.001

2.13

1.30 - 3.51

0.003

**Table 3.** Site-Specific Factors Relating With Post-Relapse Survival
Clinicopathological factors	Brain-only	Lung-only	Liver-only	Bone-only
HR: hazard ratio; 95% CI: 95% confidence interval; MBC: metastatic breast cancer; HER2: human epidermal growth factor receptor 2; NA: not available.
Age at MBC diagnosis	49	1.02	0.99 - 1.05	0.139	91	1.03	1.00 - 1.05	0.033	64	1.01	0.98 - 1.03	0.652	105	1.02	0.99 - 1.04	0.154
Histological type
Invasive ductal carcinoma	45	Reference			76	Reference			58	Reference			87	Reference
Others	4	0.60	0.18 - 1.96	0.396	15	0.99	0.44 - 2.21	0.971	6	1.73	0.67 - 4.46	0.254	18	2.30	1.22 - 4.33	0.010
Nuclear grade
Grade 1/2	11	Reference			33	Reference			30	Reference			67	Reference
Grade 3	12	2.58	0.95 - 7.05	0.064	29	2.79	1.27 - 6.13	0.011	21	1.87	0.92 - 3.79	0.084	14	1.62	0.73 - 3.62	0.238
Ki67 labeling index
Low (≤ 20%)	9	Reference			9	Reference			20	Reference			25	Reference
High (> 20%)	25	1.11	0.47 - 2.63	0.811	64	2.35	0.72 - 7.67	0.158	29	1.87	0.85 - 4.10	0.119	46	0.85	0.41 - 1.74	0.655
Molecular subtypes
Luminal	14	Reference			47	Reference			39	Reference			81	Reference
Luminal - HER2	7	0.69	0.25 - 1.90	0.476	7	1.77	0.60 - 5.24	0.304	11	0.86	0.35 - 2.10	0.738	7	1.42	0.50 - 4.02	0.507
HER2 - enriched	13	0.82	0.34 - 1.98	0.654	11	0.77	0.26 - 2.32	0.642	3	0.48	0.06 - 3.52	0.467	3	1.58	0.38 - 6.62	0.531
Triple - negative	15	1.87	0.84 - 4.18	0.126	26	3.37	1.75 - 6.48	< 0.001	11	3.19	1.46 - 6.94	0.004	14	2.29	1.15 - 4.54	0.018
Primary trigger for MBC diagnosis
Regular surveillance	2	Reference			75	Reference			46	Reference			49	Reference
Subjective symptoms	44	1.30	0.31 - 5.48	0.721	13	5.04	2.32 - 10.98	< 0.001	14	3.34	1.53 - 7.27	0.002	52	1.37	0.77 - 2.45	0.290
Local treatment for initial MBC
Yes	40	Reference			14	Reference			0	Reference			21	Reference
No	9	2.16	0.98 - 4.78	0.057	77	2.95	1.05 - 8.27	0.039	64	NA	NA	NA	84	0.45	0.25 - 0.83	0.011

Table 3. Site-Specific Factors Relating With Post-Relapse Survival

Clinicopathological factors

Brain-only

Lung-only

Liver-only

Bone-only

95% CI

P value

95% CI

P value

95% CI

P value

95% CI

P value

HR: hazard ratio; 95% CI: 95% confidence interval; MBC: metastatic breast cancer; HER2: human epidermal growth factor receptor 2; NA: not available.

Age at MBC diagnosis

1.02

0.99 - 1.05

0.139

1.03

1.00 - 1.05

0.033

1.01

0.98 - 1.03

0.652

105

1.02

0.99 - 1.04

0.154

Histological type

Invasive ductal carcinoma

Reference

Others

0.60

0.18 - 1.96

0.396

0.99

0.44 - 2.21

0.971

1.73

0.67 - 4.46

0.254

2.30

1.22 - 4.33

0.010

Nuclear grade

Grade 1/2

Reference

Grade 3

2.58

0.95 - 7.05

0.064

2.79

1.27 - 6.13

0.011

1.87

0.92 - 3.79

0.084

1.62

0.73 - 3.62

0.238

Ki67 labeling index

Low (≤ 20%)

Reference

High (> 20%)

1.11

0.47 - 2.63

0.811

2.35

0.72 - 7.67

0.158

1.87

0.85 - 4.10

0.119

0.85

0.41 - 1.74

0.655

Molecular subtypes

Luminal

Reference

Luminal - HER2

0.69

0.25 - 1.90

0.476

1.77

0.60 - 5.24

0.304

0.86

0.35 - 2.10

0.738

1.42

0.50 - 4.02

0.507

HER2 - enriched

0.82

0.34 - 1.98

0.654

0.77

0.26 - 2.32

0.642

0.48

0.06 - 3.52

0.467

1.58

0.38 - 6.62

0.531

Triple - negative

1.87

0.84 - 4.18

0.126

3.37

1.75 - 6.48

< 0.001

3.19

1.46 - 6.94

0.004

2.29

1.15 - 4.54

0.018

Primary trigger for MBC diagnosis

Regular surveillance

Reference

Subjective symptoms

1.30

0.31 - 5.48

0.721

5.04

2.32 - 10.98

< 0.001

3.34

1.53 - 7.27

0.002

1.37

0.77 - 2.45

0.290

Local treatment for initial MBC

Yes

Reference

2.16

0.98 - 4.78

0.057

2.95

1.05 - 8.27

0.039

0.45

0.25 - 0.83

0.011