Oncotype DX® and Adjuvant! Breast
Breast Cancer Res Treat
TANG: B-14/20 Adjuvant! Rev4Rev 11-29-10
28-Jun-16 12:19:39
SUPPLEMENTAL MATERIALS
Supplemental Table S1A: Comparison of the Distribution of Demographic, Clinical, and
Treatment Characteristics of NSABP B-14 Patients Who Did and Did Not Have RS
Assessment
Characteristic
Recurrence Score
Remaining B-14
All NSABP B-14
Population in B-14
Population
Population
(N = 1947)
(N = 668)
(N = 2615)
Treatment enrollment
TAM-randomized
Pts TAM-registered pts
290 (43%)
378 (57%)
1114 (57%)
833 (43%)
1404 (54%)
1211 (46%)
Age at enrollment
< 50 yr of age
50 ≤ age < 60
≥ 60 yr of age
194 (29%)
173 (26%)
301 (45%)
617 (32%)
583 (30%)
747 (38%)
811 (31%)
756 (29%)
1048 (40%)
Race
White
Black
Others
615 (92%)
31 (5%)
22 (3%)
1761 (91%)
87 (4%)
99 (5%)
2376 (91%)
118 (5%)
121 (5%)
Tumor size
0 – 1.0 cm
1.1 – 2.0 cm
2.1 – 4.0 cm
4.1+ cm
112 (17%)
303 (45%)
218 (33%)
35 (5%)
358 (18%)
898 (46%)
592 (30%)
99 (5%)
470 (18%)
1201 (46%)
810 (31%)
134 (5%)
1
Oncotype DX® and Adjuvant! Breast
Breast Cancer Res Treat
TANG: B-14/20 Adjuvant! Rev4Rev 11-29-10
28-Jun-16 12:19:39
Supplemental Table S1B: Comparison of the Distribution of Demographic, Clinical, and
Treatment Characteristics of NSABP B-20 Patients Who Did and Did Not Have RS
Assessments
Recurrence Score
Remaining B-20
NSABP B-20
Population in B-20
Population
Population
(N = 651)
(N = 1648)
(N = 2299)
227 (35%)
290 (65%)
543 (33%)
770 (33%)
1239 (67%)
1529 (67%)
289 (44%)
166 (26%)
196 (30%)
752 (46%)
478 (29%)
418 (25%)
1041 (45%)
643 (28%)
615 (27%)
Race
White
Black
Others
593 (91%)
33 (5%)
25 (4%)
1431 (87%)
103 (6%)
114 (7%)
2024 (88%)
136 (6%)
139 (6%)
Tumor size
0 – 1.0 cm
1.1 – 2.0 cm
2.1 – 4.0 cm
4.1+ cm
83 (13%)
313 (48%)
226 (35%)
29 (4%)
261 (16%)
843 (51%)
486 (29%)
58 (4%)
344 (15%)
1156 (50%)
712 (31%)
87 (4%)
Characteristic
Treatment enrollment
TAM-only
TAM + chemo
Age at enrollment
< 50 yr of age
50 ≤ age < 60
≥ 60 yr of age
2
Oncotype DX® and Adjuvant! Breast
Breast Cancer Res Treat
Models
1
TANG: B-14/20 Adjuvant! Rev4Rev 11-29-10
28-Jun-16 12:19:39
Variables
RI intermediate vs low
HR
2.51 (1.55, 4.21)
Supplemental Table S2:
3
P
0.001
Oncotype DX® and Adjuvant! Breast
Breast Cancer Res Treat
TANG: B-14/20 Adjuvant! Rev4Rev 11-29-10
28-Jun-16 12:19:39
RI high vs low
2.01 (1.25, 3.23)
RS intermediate vs low
2.21 (1.28, 3.81)
<0.001
2
RS high vs low
3.8 (2.36, 6.1)
Age (>50 vs <=50)
0.76 (0.52, 1.13)
0.173
Tumor size
1.2(1.07, 1.36)
0.003
Grade (moderate vs well) 1.51 (0.75, 3.05)
Grade (poor vs well)
3.18 (1.42, 7.15)
RI intermediate vs low
1.51 (0.82, 2.78)
RI high vs low
0.95 (0.52, 1.76)
RS intermediate vs low
2.07 (1.18, 3.61)
RS high vs low
2.88 (1.74, 4.76)
0.003
0.176
<0.001
Results of Multivariate Cox Models Assessing the Relative Associations of RS and RI
Risk Groups among 668 B-14 Tamoxifen-treated Patients using DRFI as the Endpoint
4
Oncotype DX® and Adjuvant! Breast
Breast Cancer Res Treat
TANG: B-14/20 Adjuvant! Rev4Rev 11-29-10
28-Jun-16 12:19:39
Supplemental Table S3: Results from Multivariate Cox Models Assessing the Relative
Associations of RI-PCT/50 and RS-PCT/50 among 668 B-14 Tamoxifen-treated Patients
Using Breast Cancer-specific Mortality as the Endpoint
Models
Variables
Age (>50 vs <=50)
Tumor size (cm)
1
Grade (moderate vs well)
Grade (poor vs well)
Hazard ratio (95% CI)
0.81 (0.55, 1.21)
1.21 (1.1, 1.35)
2.71 (1.46, 5.06)
P
0.3
-2log(L)a
1270.6
<0.001
<0.001
6.45 (3.48, 11.94)
2
RI-PCT/50
3.28 (2.2, 4.89)
<0.001
1295.7
3
RS-PCT/50
3.32 (2.29, 4.81)
<0.001
1288.9
RI-PCT/50
2.31 (1.51, 3.53)
<0.001
1273.1
RS-PCT/50
2.45 (1.66, 3.61)
<0.001
Age (>50 vs <=50)
0.87 (0.58, 1.29)
0.49
Tumor size (cm)
1.22 (1.05, 1.41)
0.008
4
5
6
7
Grade (moderate vs well) 2.24 (1.07, 4.72)
0.001
Grade (poor vs well)
4.35 (1.86, 10.15)
RI-PCT/50
0.93 (0.49, 1.78)
0.83
RS-PCT/50
2.02 (1.35, 3)
<0.001
Age (>50 vs <=50)
0.87 (0.59, 1.29)
0.49
Tumor size (cm)
1.2 (1.08, 1.34)
<0.001
Grade (moderate vs well) 2.15 (1.14, 4.07)
4.11 (2.11, 8.01)
RS-PCT/50
2.01 (1.35, 2.98)
<0.001
Age (>50 vs <=50)
0.81 (0.55, 1.21)
0.31
Tumor size (cm)
1.2 (1.05, 1.38)
0.01
<0.001
5
1257.8
<0.001
Grade (poor vs well)
Grade (moderate vs well) 2.59 (1.24, 5.4)
1257.8
1270.5
Oncotype DX® and Adjuvant! Breast
Breast Cancer Res Treat
aL
TANG: B-14/20 Adjuvant! Rev4Rev 11-29-10
28-Jun-16 12:19:39
Grade (poor vs well)
6.04 (2.67, 13.71)
RI-PCT/50
1.08 (0.57, 2.03)
represents the likelihood function for a model.
6
0.82
Oncotype DX® and Adjuvant! Breast
Breast Cancer Res Treat
TANG: B-14/20 Adjuvant! Rev4Rev 11-29-10
28-Jun-16 12:19:39
Supplemental Table S4: Results from Multivariate Cox Models Assessing the Relative
Associations of RI-PCT/50 and RS-PCT/50 among 668 B-14 Tamoxifen-treated
Models
Variables
Hazard ratio (95% CI)
P
-2log(L)a
Age (>50 vs <=50)
1.48 (1.06, 2.05)
0.021
2324.1
Tumor size (cm)
1.1 (1, 1.21)
0.047
Grade (moderate vs well)
1.66 (1.15, 2.39)
Grade (poor vs well)
2.68 (1.8, 3.99)
2
RI-PCT/50
1.63 (1.24, 2.14)
<0.001
2342.9
3
RS-PCT/50
1.95 (1.51, 2.52)
<0.001
2328.9
RI-PCT/50
1.31 (0.98, 1.75)
0.074
2325.6
RS-PCT/50
1.77 (1.35, 2.33)
<0.001
Age (>50 vs <=50)
1.55 (1.11, 2.16)
0.01
Tumor size (cm)
1.14 (1, 1.29)
0.057
1
<0.001
4
5
6
7
Grade (moderate vs well) 1.63 (1.01, 2.61)
0.013
Grade (poor vs well)
2.4 (1.33, 4.33)
RI-PCT/50
0.77 (0.47, 1.26)
0.3
RS-PCT/50
1.67 (1.26, 2.22)
<0.001
Age (>50 vs <=50)
1.56 (1.12, 2.17)
0.01
Tumor size (cm)
1.08 (0.98, 1.19)
0.13
Grade (moderate vs well) 1.4 (0.96, 2.05)
1.95 (1.26, 3.02)
RS-PCT/50
1.65 (1.24, 2.19)
<0.001
Age (>50 vs <=50)
1.47 (1.06, 2.05)
0.022
Tumor size (cm)
1.14 (1, 1.29)
0.045
<0.001
7
2311.8
0.011
Grade (poor vs well)
Grade (moderate vs well) 1.85 (1.16, 2.94)
2310.7
2323.6
Oncotype DX® and Adjuvant! Breast
Breast Cancer Res Treat
TANG: B-14/20 Adjuvant! Rev4Rev 11-29-10
28-Jun-16 12:19:39
Grade (poor vs well)
3.12 (1.77, 5.5)
RI-PCT/50
0.83 (0.51, 1.35)
0.462
Patients Using Overall Survival as the Endpoint
aL
represents the likelihood function for a model.
Supplemental Table S5: Results from Multivariate Cox Models Assessing the Relative
Associations of RI-PCT/50 and RS-PCT/50 among 668 B-14 Tamoxifen-treated
Models
Variables
Hazard ratio (95% CI)
P
Age (>50 vs <=50)
1.15 (0.89,1.5)
0.287
Tumor size (cm)
1.06 (0.98, 1.15)
0.13
Grade (moderate vs well)
1.19 (0.9, 1.58)
-2log(L)a
3453.4
1
0.002
Grade (poor vs well)
1.77 (1.29, 2.43)
2
RI-PCT/50
1.3 (1.04, 1.61)
0.021
3463.8
3
RS-PCT/50
1.77(1.44, 2.18)
<0.001
3439.5
RI-PCT/50
1.05(0.83,1.33)
0.69
3439.3
RS-PCT/50
1.75(1.4, 2.18)
<0.001
Age (>50 vs <=50)
1.2(0.99,1.24)
0.175
Tumor size (cm)
1.11(0.99,1.24)
0.07
4
5
Grade (moderate vs well) 1.17 (0.8, 1.7)
0.12
Grade (poor vs well)
1.58 (0.97,2.56)
RI-PCT/50
0.76 (0.5, 1.15)
0.188
RS-PCT/50
1.69 (1.34, 2.14)
<0.001
8
3432.6
Oncotype DX® and Adjuvant! Breast
Breast Cancer Res Treat
6
7
TANG: B-14/20 Adjuvant! Rev4Rev 11-29-10
28-Jun-16 12:19:39
Age (>50 vs <=50)
1.21(0.93,1.57)
0.161
Tumor size (cm)
1.05 (0.96,1.14)
0.27
Grade (moderate vs well) 1 (0.75,1.34)
3434.3
0.268
Grade (poor vs well)
1.27 (0.89,1.81)
RS-PCT/50
1.67(1.32,2.11)
<0.001
Age (>50 vs <=50)
1.15(0.88,1.49)
0.3
Tumor size (cm)
1.1 (0.99,1.23)
0.07
Grade (moderate vs well) 1.33 (0.92,1.93)
Grade (poor vs well)
2.07 (1.31,3.29)
RI-PCT/50
0.83 (0.55, 1.24)
3452.6
0.004
0.357
Patients Using DFS as the Endpoint
aL
represents the likelihood function for a model.
Supplemental Table S6: Association between RS or RI Risk Groups and Benefit from
Chemotherapy among 651 B-20 Patients using Breast Cancer-specific Mortality as the
Endpoint
Cohort
HR for benefit
Pa
Pb (interaction)
from MF/CMF (95%
CI)
Overall
0.62 (0.36, 1.06)
0.081
RS low
1.86 (0.38, 9.19)
0.449
RS intermediate
0.94 (0.32, 2.82)
0.918
RS high
0.27 (0.13, 0.55)
<0.001
9
0.025
Oncotype DX® and Adjuvant! Breast
Breast Cancer Res Treat
TANG: B-14/20 Adjuvant! Rev4Rev 11-29-10
28-Jun-16 12:19:39
Adjuvant! low
1.03 (0.35, 3.01)
0.96
Adjuvant!
0.62 (0.23, 1.71)
0.358
0.44 (0.19, 1.02)
0.054
intermediate
Adjuvant! high
a From
Wald tests.
b From
likelihood ratio tests.
10
0.463
Oncotype DX® and Adjuvant! Breast
Breast Cancer Res Treat
TANG: B-14/20 Adjuvant! Rev4Rev 11-29-10
28-Jun-16 12:19:39
SUPPLEMENTAL FIGURES
SUPPLEMENTAL FIGURES LEGENDS
Fig. S1 Kaplan-Meier curves for distant recurrence across RS risk groups in B-14
tamoxifen-treated patients.
Fig. S2 Kaplan-Meier curves for distant recurrence across RI risk groups in B-14
tamoxifen-treated patients.
Fig. S3 Point estimates and 95% confidence intervals for the percentage of
B-14 patients with distant recurrence at 10 years by RS then RI risk groups.
11
Oncotype DX® and Adjuvant! Breast
Breast Cancer Res Treat
TANG: B-14/20 Adjuvant! Rev4Rev 11-29-10
28-Jun-16 12:19:39
Fig. S1 Kaplan-Meier curves for distant recurrence across RS risk groups in B-14
0.8
0.6
0.4
RS Risk Groups
Low
Intermediate
High
0.2
Number of Patients at Risk:
0.0
Proportion of Free From Distant Recurrence
1.0
tamoxifen-treated patients.
0
338
328
313
298
276
258
231
169
149
139
128
116
104
96
80
66
181
157
140
123
111
99
90
70
2
4
6
8
10
Time in Years
12
12
14
Oncotype DX® and Adjuvant! Breast
Breast Cancer Res Treat
TANG: B-14/20 Adjuvant! Rev4Rev 11-29-10
28-Jun-16 12:19:39
Fig. S2 Kaplan-Meier curves for distant recurrence across RI risk groups in B-14
0.8
0.6
0.4
Adjuvant! Risk Groups
Low
Intermediate
High
0.2
Number of Patients at Risk:
0.0
Proportion of Free From Distant Recurrence
1.0
tamoxifen-treated patients.
0
352
337
322
297
267
248
219
170
124
112
101
94
86
78
73
52
192
175
158
146
138
127
109
83
2
4
6
8
10
12
Time in Years
13
14
Oncotype DX® and Adjuvant! Breast
Breast Cancer Res Treat
TANG: B-14/20 Adjuvant! Rev4Rev 11-29-10
28-Jun-16 12:19:39
Fig. S3 Point estimates and 95% confidence intervals for the percentage of
B-14 patients with distant recurrence at 10 years by RS then RI risk groups.
All Patients
No. of
Patients
668
RS Low
Adjuvant! Low
Adjuvant! Intermediate
Adjuvant! High
338
216
57
65
RS Intermediate
Adjuvant! Low
Adjuvant! Intermediate
Adjuvant! High
149
84
24
41
RS High
Adjuvant! Low
Adjuvant! Intermediate
Adjuvant! High
181
52
43
86
0
14
5
10
15
20
25
30
35
40
45
50
Percentage of Distant
Recurrence After 10 Years