Analysis of clinicopathological features and prognostic factors of breast cancer brain metastasis

Table 1 Clinicopathological features and tumor characteristics of patients

Item	Non-BCBM group (n = 136) [n (%)]	BCBM group (n = 68) [n (%)]	P
Age at diagnosis of BC (yr)			0.009
≤ 35	9 (6.6)	12 (17.6)
35-55	79 (58.1)	43 (63.2)
> 55	48 (35.3)	13 (19.2)
Menstrual status at diagnosis of BC			0.77
Premenopause	69 (50.7)	33 (48.5)
Menopause	67 (49.3)	35 (51.5)
Family history of cancer			0.12
None	112 (82.4)	60 (88.2)
Other malignancies	16 (11.8)	8 (11.8)
BC	8 (5.9)	0 (0.0)
Lymph node stage			0.01
N0	56 (41.2)	19 (27.9)
N1	43 (31.6)	14 (20.6)
N2	25 (18.4)	17 (25.0)
N3	12 (8.8)	15 (22.1)
Missing	0 (0.0)	3 (4.4)
Tumor size			0.17
T1	53 (39.0)	18 (26.5)
T2	67 (49.3)	37 (54.4)
T3	13 (9.6)	11 (16.2)
T4	1 (0.7)	0 (0.0)
Missing	2 (1.5)	2 (2.9)
Tumor stage at the initial diagnosis			< 0.001
IA	29 (21.3)	3 (4.4)
IIA	39 (28.7)	19 (27.9)
IIB	29 (21.3)	7 (10.3)
IIIA	22 (16.2)	17 (25.0)
IIIB	2 (1.5)	0 (0.0)
IIIC	11 (8.1)	11 (16.2)
IV	3 (2.2)	7 (10.3)
Missing	1 (0.7)	4 (5.9)
ER			0.009
Negative	42 (30.9)	32 (47.1)
Positive	94 (69.1)	32 (47.1)
Missing	0 (0.0)	4 (5.9)
PR			0.003
Negative	52 (38.2)	39 (57.4)
Positive	84 (61.8)	25 (36.8)
Missing	0 (0.0)	4 (5.9)
Molecular type			< 0.001
Luminal A type	71 (52.2)	13 (19.1)
Luminal B type	28 (20.6)	22 (32.4)
HER2-overexpressing type	18 (13.2)	14 (20.6)
Triple-negative type	19 (14.0)	14 (20.6)
Missing	0 (0.0)	5 (7.4)
Pathological type			0.42
Noninvasive carcinoma	10 (7.4)	2 (2.9)
Invasive ductal carcinoma	95 (69.9)	51 (75.0)
Invasive lobular carcinoma	5 (3.7)	2 (2.9)
Others	26 (19.1)	8 (11.8)
Missing	0 (0.0)	5 (7.4)
Metastasis
Bone metastasis			< 0.001
Yes	12 (8.8)	38 (55.9)
No	124 (91.2)	30 (44.1)
Liver metastasis			< 0.001
Yes	7 (5.1)	20 (29.4)
No	129 (94.9)	48 (70.6)
Lung metastasis			< 0.001
Yes	8 (5.9)	35 (51.5)
No	128 (94.1)	33 (48.5)
Number of liver, lung and bone metastases			< 0.001
0	123 (90.4)	21 (30.9)
1	8 (5.9)	19 (27.9)
2	3 (2.2)	18 (26.5)
3	2 (1.5)	10 (14.7)
Number of metastases to other sites			< 0.001
0	118 (86.8)	33 (48.5)
1	15 (11.0)	24 (35.3)
2	2 (1.5)	8 (11.8)
3	1 (0.7)	3 (4.4)
Surgical treatment			< 0.001
No	3 (2.2)	7 (10.3)
Breast-conserving surgery	20 (14.7)	5 (7.4)
Modified radical mastectomy	106 (77.9)	43 (63.2)
Others	7 (5.1)	13 (19.1)
Radiotherapy			0.006
No	76 (55.9)	24 (35.3)
Yes	60 (44.1)	44 (64.7)
Chemotherapy
Neoadjuvant chemotherapy			0.21
No	119 (87.5)	55 (80.9)
Yes	17 (12.5)	13 (19.1)
Anthracyclines			< 0.001
No	28 (20.6)	35 (51.5)
Yes	107 (78.7)	32 (47.1)
Missing	1 (0.7)	1 (1.5)
Taxane			0.35
No	35 (25.7)	22 (32.4)
Yes	101 (74.3)	46 (67.6)
HER2 targeted therapy			< 0.001
No	118 (86.8)	36 (52.9)
Yes	18 (13.2)	32 (47.1)

BC: Breast cancer; BCBM: Breast cancer brain metastasis; ER: Estrogen receptor; PR: Progesterone receptor; HER2: Human epidermal growth factor receptor 2.

Table 2 High-risk factors of breast cancer brain metastasis

Item	Univariate Cox		Multivariate Cox
	HR (95%CI)	P	HR (95%CI)	P
Age at diagnosis of BC (yr)
≤ 35	Reference
> 35	0.008 (0-1.89)	0.083
Menstrual status at diagnosis of BC
Premenopause	Reference
Menopause	1.29 (0.52-3.20)	0.59
Family history of cancer
None	Reference
Yes	0.62 (0.26-1.44)	0.26
Lymph node stage
N0-N1	Reference
N2-N3	2.77 (1.40-5.48)	0.004	NS
Tumor size
T1-T2	Reference
T3-T4	1.44 (0.65-3.15)	0.37
Tumor stage at the initial diagnosis
I-II	Reference
III-IV	3.84 (1.89-7.78)	< 0.001	5.58 (1.99-15.68)	0.001
ER
Negative	Reference
Positive	0.49 (0.27-0.87)	0.015	NS
PR
Negative	Reference
Positive	0.36 (0.18-0.69)	0.002	NS
Molecular type
Luminal A type	Reference
Luminal B type	3.95 (1.71-9.14)	0.001	5.36 (1.61-17.76)	0.006
HER2-overexpression type	4.01 (1.61-9.96)	0.003	5.0 (1.30-19.25)	0.019
Triple-negative type	4.34 (1.55-12.11)	0.005	NS	NS
Pathological type
Others	Reference
Invasive ductal carcinoma	1.83 (0.83-4.05)	0.14
Invasive lobular carcinoma	1.31 (0.22-7.69)	0. 77
Surgical treatment
Others	Reference
Modified radical mastectomy	0.48 (0.26-0.90)	0.021	NS
Bone metastasis
No	Reference
Yes	7.19 (3.13-16.52)	< 0.001	NS
Liver metastasis
No	Reference
Yes	7.44 (2.77-20.01)	< 0.001	NS
Lung metastasis
No	Reference
Yes	15.87 (5.61-44.89)	< 0.001	24.18 (6.40-91.43)	< 0.001
Number of liver, lung and bone metastases
< 2	Reference
≥ 2	17.78 (5.38-58.73)	< 0.001	NS
Number of metastases to other sites
< 2	Reference
≥ 2	7.33 (2.05-26.27)	0.002	NS

95%CI: 95% confidence interval; NS: Not statistically significant; HR: Hazard ratio; ER: Estrogen receptor; PR: Progesterone receptor; BC: Breast Cancer; HER2: Human epidermal growth factor receptor 2.

Table 3 Prognostic factors of breast cancer brain metastasis

Item	Univariate Cox		Multivariate Cox
	HR (95%CI)	P	HR (95%CI)	P
Age at diagnosis of BM (yr)
≤ 35	Reference
> 35	1.033 (0.315-3.385)	0.957
Time from BC to BM (mo)
≤ 24	Reference
> 24	0.896 (0.482-1.664)	0.727
Menstrual status at diagnosis of BM
Premenopause	Reference
Menopause	0.685 (0.331-1.416)	0.307
Molecular type
Luminal A type	0.253 (0.087-0.730)	0.011	0.227 (0.074-0.693)	0.009
Luminal B type	0.279 (0.128-0.607)	0.001	0.293 (0.129-0.663)	0.003
HER2-overexpressing type	0.274 (0.121-0.618)	0.002	0.319 (0.135-0.754)	0.009
Triple-negative type	Reference
Bone metastasis
No	Reference
Yes	1.980 (1.135-3.453)	0.016	2.011 (1.056-3.831)	0.034
Liver metastasis
No	Reference
Yes	1.121 (0.626-2.007)	0.701
Lung metastasis
No	Reference
Yes	1.616 (0.929-2.810)	0.089
Number of liver, lung and bone metastases
≤ 2	Reference
> 2	1.548 (0.894-2.682)	0.119
Number of metastases to other sites
< 2	Reference
≥ 2	1.425 (0.711-2.858)	0.318
Tumor stage
I-II	Reference
III-IV	0.813 (0.466-1.419)	0.466
Lymph node stage
N0-N1	Reference
N2-N3	0.843 (0.486-1.464)	0.545
Pathological type
Others	0.287 (0.073-1.133)	0.075
Invasive lobular carcinoma	Reference
Invasive ductal carcinoma	0.208 (0.060-0.725)	0.014	NS
Symptoms
No	Reference
Yes	2.171 (1.191-3.959)	0.011	1.923 (1.005-3.680)	0.048
Size of BM (cm)
≤ 3	Reference
> 3	0.803 (0.449-1.439)	0.462
Number of BM
≤ 3	Reference
> 3	1.248 (0.721-2.160)	0.428
Surgery for BM
No	Reference
Yes	0.744 (0.348-1.591)	0.446
Treatment after BM
Local therapy	Reference
Medication alone	1.531 (0.638-3.674)	0.064
Systemic therapy	0.748 (0.317-1.765)	0.507
Local therapy
SRT	1.350 (0.513-3.549)	0.543
WBRT	1.600 (0.633-4.043)	0.320
Both	1.935 (0.680-5.506)	0.216
Neither	Reference

95%CI: 95% confidence interval; NS: Not statistically significant; HR: Hazard ratio; BC: Breast Cancer; BM：Brain Metastasis; WBRT: Whole brain radiation therapy; SRT: Stereotactic radiotherapy; HER2: Human epidermal growth factor receptor 2.

Table 4 Treatment methods of brain metastasis

Item	Patients with BM (n = 68)	Median survival time (mo)
Medication	7	12
MDT	27	21
Local therapy alone	30	15
Neither	4
Local therapy	n = 57
SRT alone	19	16
Surgery + SRT	6	19
SRT + WBRT	10	18
Surgery + WBRT	3	30
WBRT	17	12
Surgery + SRT + WBRT	2	21
HER2 targeted therapy	n = 16
Trastuzumab	5	17
Trastuzumab + pertuzumab	2
Trastuzumab + TKI	2	23
Capecitabine + TKI	7	54

MDT: Multidisciplinary treatment; WBRT: Whole brain radiation therapy; SRT: Stereotactic radiotherapy; TKI: Trastuzumab plus tyrosine kinase inhibitors; BM: Brain Metastasis; HER2: Human epidermal growth factor receptor 2.