1. GOCS GRUPO ONCOLÓGICO COOPERATIVO DEL SUR
Prognostic factors and survival according to tumor subtype in women presenting with
breast cancer brain metastases at initial diagnosis.
GOCS GRUPO ONCOLÓGICO COOPERATIVO DEL SUR
ARGENTINA
J.P. Leone1, A.O. Zwenger2, J. Iturbe2, J. Leone2, B.A. Leone2, C.T. Vallejo2
Background
Results
Breast cancer represents one of the most common causes of brain metastases. The occurrence of this event is a catastrophic complication of metastatic breast cancer, associated with poor prognosis, significant morbidity and reduced quality of life.
Brain metastases generally occur as a late event in the natural course of breast cancer. The presence of brain metastases at the time of initial breast cancer diagnosis (BMIBCD) is less common. There is a lack of data about patient characteristics and prognostic factors in this unique group of patients, which makes the prognostic assessment and management very challenging.
A total of 740 patients were included in this study. Median age was 60 years (range 26-93). Median follow-up was 6 months (range 1-48). OS at 1 and 3 years were 44.6% and 20.7%, respectively. There were 471 deaths reported.
At diagnosis, brain was the only site of metastasis in 125 patients, whereas 66.2% had metastases in bone, 33.2% in liver and 44.7% in lung. Among patients with known variables, 56.5% had grade III/IV tumors, 46.6% were HR+/HER2-, 17% HR+/HER2+, 14.1% HR-/HER2+ and 22.3% TNBC.
Table 1 shows the patient characteristics according to tumor subtype. Patients with TNBC had higher tumor grade (p<0.0001), higher rates of brain only (p=0.001) and lung metastases (p=0.037), lower rate of bone metastases (p<0.0001) and were more likely to die from breast cancer (p<0.0001).
Table 2. Univariate and Multivariate Analysis
Variable
Log-Rank P
Cox P HR
95.0% CI for HR
Lower
Upper
Age at diagnosis, y
0.0002
<50 years
Reference
50-64 years
0.850
1.033
0.741
1.439
>64 years
0.001
1.840
1.276
2.653
Race
0.0041
White
Black
0.051
1.397
0.999
1.953
Other (American Indian/AK Native, Asian/Pacific Islander)
0.937
1.020
0.631
1.649
Grade
0.0696 I II
0.131
1.626
0.865
3.057
III/IV
0.081
1.765
0.932
3.342
Histology
0.0145
Ductal
Lobular
0.006
2.081
1.238
3.496
Mixed ductal and lobular
0.199
0.552
0.223
1.366
Mucinous
0.359
0.394
0.054
2.881
Carcinoma
0.435
1.181
0.777
1.795
Tumor subtype
<0.0001
HR-positive/HER2-negative
Triple negative
0.010
1.541
1.108
2.143
HR-positive/HER2-positive
0.059
0.685
0.462
1.014
HR-negative/HER2-positive
0.325
1.222
0.820
1.821
Sites of metastases
Bone (Yes vs No)
0.1823
0.780
1.054
0.730
1.521
Liver (Yes vs No)
1.645
1.236
2.190
Lung (Yes vs No)
0.002
0.288
1.170
0.876
1.563
Brain only (Yes vs No)
0.1597
0.696
1.102
0.678
1.789
Marital status
0.0165
Single
Married
0.047
0.715
0.513
0.996
Other (Separated/Divorced/Widowed)
0.546
0.898
0.633
1.273
Objective
Analysis of OS for the entire cohort. Median OS 10 months.
Table 1. Patient Characteristics
The aim of this study was to analyze the influence of tumor subtype compared with other prognostic factors in the survival of patients who present with BMIBCD.
Tumor subtype:
HR-positive/HER2-negative
HR-positive/HER2-positive
HR-negative/HER2-positive
Triple negative
Unknown*
Total N % P
All patients
293
39.6%
107
14.5% 89
12.0%
140
18.9%
111
15.0%
740
100.0%
Age at diagnosis, y
<50 54
18.4% 25
23.4% 26
29.2% 35
25.0% 9
8.1%
149
20.1%
0.005
50-64
125
42.7% 59
55.1% 44
49.4% 62
44.3%
48.6%
344
46.5%
>64
114
38.9% 23
21.5% 19
21.3% 43
30.7% 48
43.2%
247
33.4%
Race
White
231
78.8% 78
72.9%
69.7%
105
75.0% 73
65.8%
549
74.2%
0.19
Black 46
15.7% 16 28
20.0% 33
29.7%
142
19.2%
Other 15
5.1% 12
11.2% 8
9.0% 7
5.0% 5
4.5% 47
6.4% 1
.3%
.9%
0.0% 2
Grade I 20
6.8% 3
2.1%
1.8%
3.5%
<0.0001 II
112
38.2% 34
31.8%
22.5%
14.3% 22
19.8%
208
28.1%
III/IV
30.4% 49
45.8%
53.9%
63.6% 29
26.1%
304
41.1% 72
24.6% 21
23.6% 58
52.3%
202
27.3%
Histology
Ductal
213
72.7% 92
86.0% 68
76.4%
113
80.7% 76
68.5%
562
75.9%
0.002
Lobular
9.9%
2.8%
1.1% 38
Ductal and lobular 6
2.0%
4.7%
2.2% 17
2.3%
Mucinous
1.7%
.7%
Carcinoma 40
13.7%
5.6% 18
20.2% 32
28.8%
116
Bone metastases No 65
22.2%
36.0%
54.3%
246
33.2%
Yes
224
76.5% 82
76.6% 55
61.8% 60
54.1%
483
65.3% 4
1.4%
2.7% 11
1.5%
Liver metastases
198
67.6% 94
67.1%
61.3%
472
63.8%
0.012
28.0% 41
46.1% 42
30.0% 36
32.4%
235 13
4.4%
2.9%
6.3%
Lung metastases
162
55.3%
60.7% 39
43.8% 66
47.1% 53
47.7%
385
52.0%
0.037
115
39.2%
32.7%
44.9% 70
50.0% 52
46.8%
312
42.2%
5.5%
6.5% 10
5.4%
5.8%
Brain metastases only
249
85.0% 93
86.9%
80.9% 98
70.0%
80.2%
601
81.2%
0.001
13.0% 14
13.1%
28.6%
17.1%
16.9%
3.4%
1.9%
Marital status at diagnosis
Single 71
24.2%
26.2%
16.4%
169
22.8%
0.12
Married
118
40.3%
49.5% 37
41.6%
31.5%
305
41.2% 81
27.6%
37.1%
36.9%
225
7.8%
6.7%
Status
Alive
121
41.3% 57
53.3%
20.7% 30
27.0%
269
36.4%
Dead
172
58.7% 50
46.7%
64.0%
79.3%
73.0%
471
Cause of Death
Breast cancer
161
54.9%
106
75.7% 77
69.4%
447
60.4%
3.8%
3.6% 24
3.2%
*Unknown patients are excluded from the comparative analysis
Materials and Methods
We obtained data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) program, using the 18 registry ( ) database.
We extracted all cases of women with brain metastases at the time of initial diagnosis of microscopically confirmed stage IV breast cancer diagnosed between 2010 and Patients with other primary neoplasms either before or after breast cancer were excluded.
The following variables were analyzed: age at diagnosis, race, year of diagnosis, grade, histology, ER, PR, HER2, type of breast surgery, radiation therapy, laterality, marital status, site of metastases, survival months, vital status and cause of death.
Patient characteristics were compared between tumor subtypes using chi2 or Fisher’s exact tests.
Survival probabilities were estimated using the Kaplan Meier method.
Log-Rank test analyzed differences in overall survival (OS) between groups.
Univariate and multivariate analyses were performed to determine the effect of each variable on OS.
OS was shorter for patients with triple negative tumors (P=<0.0001).
Conclusions
Although the prognosis is generally poor, 20.7% of patients were still alive 3 years after diagnosis.
There were substantial differences in OS according to tumor subtype.
The HR+/HER2- group represented the largest proportion of cases.
In addition to tumor subtype, other independent predictors of OS are age at diagnosis, marital status, histology and liver metastases.
Analysis of OS according to liver metastases showed significantly longer survival for patients with no liver involvement (P=<0.0001).
1University of Iowa Holden Comprehensive Cancer Center and Iowa City VA Medical Center, 2Grupo Oncológico Cooperativo del Sur, Argentina