Introduction
Methods
Data source
Patient selection
Definition of HER2 subgroups
Covariates of interest
Tumor characteristics
Patient characteristics
Statistical analyses
Study cohort characterization
Sites of recurrence analysis
Agreement between primary and metastatic samples analysis
Survival outcomes analysis
Results
Description of the study cohort
Clinicopathological characteristics and patterns of care
At time of diagnosis of index cancer
| ||||
---|---|---|---|---|
Variable N (%) | Total (N = 3394) | HR-positive (n = 2015) | HR-negative (n = 1379) | P-value |
Age, mean (se), y
| 52.48 (0.21) | 52.41 (0.29) | 52.59 (0.32) | |
Age category, N, (%)
| <.001 | |||
0 to <50
| 1,514 (45) | 931 (46) | 583 (42) | |
50 to <70
| 1,547 (46) | 865 (43) | 682 (49) | |
70+
| 333 (10) | 219 (11) | 114 (8) | |
Race/Ethnicity, N, (%)
| 0.030 | |||
African-American
| 259 (8) | 135 (7) | 124 (9) | |
Caucasian
| 2,693 (79) | 1,627 (81) | 1,066 (77) | |
Hispanic
| 262 (8) | 155 (8) | 107 (8) | |
Asian Pacific Island
| 126 (4) | 64 (3) | 62 (5) | |
American Indian
| 10 (<1) | 4 (<1) | 6 (<1) | |
Other
| 16 (<1) | 10 (1) | 6 (<1) | |
Unknown
| 28 (1) | 20 (1) | 8 (1) | |
Menopausal Status, N, (%)
| 0.001 | |||
Premenopausal
| 1,569 (46) | 978 (49) | 591 (43) | |
Postmenopausal
| 1,825 (54) | 1,037 (51) | 788 (57) | |
Body Mass Index kg/m2, N, (%)
| 0.512 | |||
<18.5 kg/m2 (Underweight)
| 52 (2) | 34 (2) | 18 (1) | |
18.5 to <25 kg/m2 (Normal)
| 1,263 (37) | 750 (37) | 513 (37) | |
25 to <30 kg/m2 (Obese)
| 913 (27) | 554 (27) | 359 (26) | |
>30 kg/m2 (Severely Obese)
| 884 (26) | 506 (25) | 378 (27) | |
Missing/unknown
| 282 (8) | 171 (8) | 111 (8) | |
Co-morbidity score, N, (%)
| 0.958 | |||
0
| 2,713 (80) | 1,609 (80) | 1,104 (80) | |
1
| 452 (13) | 271 (13) | 181 (13) | |
2+
| 229 (7) | 135 (7) | 94 (7) | |
Method of detection, N, (%)
| <.001 | |||
Abnormal screening mammogram
| 1,209 (36) | 755 (37) | 454 (33) | |
Symptom
| 2,012 (59) | 1,175 (58) | 837 (61) | |
Other
| 147 (4) | 67 (3) | 80 (6) | |
Unknown
| 26 (1) | 18 (1) | 8 (1) | |
T stage, category, N, (%)
| <.001 | |||
T1
| 1,753 (52) | 1,103 (55) | 650 (47) | |
T2
| 1,150 (34) | 691 (34) | 459 (33) | |
T3
| 244 (7) | 129 (6) | 115 (8) | |
T4
| 197 (6) | 73 (4) | 124 (9) | |
Unknown
| 50 (1) | 19 (1) | 31 (2) | |
Nodal status, N, (%)
| <.001 | |||
Positive
| 1,623 (48) | 907 (45) | 716 (52) | |
Negative
| 1,757 (52) | 1,101 (55) | 656 (48) | |
Unknown
| 14 (<1) | 7 (<1) | 7 (<1) | |
AJCC stage, N, (%)
| <.001 | |||
I
| 1,187 (35) | 772 (38) | 415 (30) | |
II
| 1,467 (43) | 887 (44) | 580 (42) | |
III
| 740 (22) | 356 (18) | 384 (28) | |
Histologic grade, N, (%)
| <.001 | |||
Low/Intermediate
| 907 (27) | 719 (36) | 188 (14) | |
High
| 2,324 (68) | 1,211 (60) | 1,113 (81) | |
Unknown
| 163 (5) | 85 (4) | 78 (6) | |
Histology, N, (%)
| <.001 | |||
Invasive ductal
| 3,101 (91) | 1,772 (88) | 1,329 (97) | |
Invasive lobular
| 105 (3) | 89 (4) | 16 (1) | |
Mixed ductal and lobular
| 139 (4) | 120 (6) | 19 (1) | |
Other
| 49 (1) | 34 (2) | 15 (1) | |
LVI, N, (%)
| 0.630 | |||
Presence
| 1,164 (34) | 678 (34) | 486 (35) | |
Absence
| 2,113 (62) | 1,267 (63) | 846 (61) | |
Unknown
| 117 (3) | 70 (3) | 47 (3) | |
EIC, N, (%)
| 0.536 | |||
Presence
| 606 (18) | 353 (18) | 253 (18) | |
Absence
| 2,788 (82) | 1,662 (82) | 1,126 (82) | |
In patients with documented recurrence
| ||||
Variable
|
Total
N = 458 |
HR-positive
N = 208 |
HR-negative
N = 250 |
P
-value
|
Disease free interval median (range), y
| 1.95 (7.69) | 2.24 (7.69) | 1.70 (7.08) | |
Age, mean (se), y
| 50.95 (0.60) | 50.39 (0.94) | 51.41 (0.78) | |
Race/Ethnicity, N, (%)
| 0.644 | |||
African-American
| 51 (11) | 21 (10) | 30 (12) | |
Caucasian
| 358 (78) | 166 (80) | 192 (77) | |
Hispanic
| 31 (7) | 12 (6) | 19 (8) | |
Asian Pacific Island
| 12 (3) | 6 (3) | 6 (2) | |
American Indian
| 1 (<1) | 1 (<1) | 0 (0) | |
Other
| 4 (1) | 1 (<1) | 3 (1) | |
Unknown
| 1 (<1) | 1 (<1) | 0 (0) | |
Menopausal status at time of diagnosis of index cancer, N, (%)
| 0.207 | |||
Premenopausal
| 223 (49) | 108 (52) | 115 (46) | |
Postmenopausal
| 235 (51) | 100 (48) | 135 (54) | |
Co-morbidity score at time of diagnosis of index cancer, N, (%)
| 0.437 | |||
0
| 371 (81) | 166 (80) | 205 (82) | |
1
| 57 (12) | 25 (12) | 32 (13) | |
2+
| 30 (7) | 17 (8) | 13 (5) | |
AJCC stage at time of diagnosis of index cancer, N, (%)
| 0.437 | |||
I
| 77 (17) | 36 (17) | 41 (16) | |
II
| 188 (41) | 91 (44) | 97 (39) | |
III
| 193 (42) | 81 (39) | 112 (45) | |
Histologic grade at time of diagnosis of index cancer, N, (%)
| 0.016 | |||
Low/Intermediate
| 65 (14) | 40 (19) | 25 (10) | |
High
| 379 (83) | 163 (79) | 216 (86) | |
Unknown
| 14 (3) | 5 (2) | 9 (4) |
Patterns of recurrence
Type of first recurrence by HR
Univariate analysis OR (95% CI) | P-value | Multivariable analysis OR (95% CI) | P-value | |
---|---|---|---|---|
HR-negative vs. HR-positive | HR-negative vs. HR-positive | |||
Local regional
vs. Distant
| 1.06 (0.71, 1.59) | 0.772 | 1.15 (0.75, 1.76) | 0.531 |
Brain vs. Other
| 1.75 (1.05, 2.93) | 0.033 | 1.63 (0.95, 2.81) | 0.079 |
Bone vs. Other
| 0.53 (0.34, 0.82) | 0.005 | 0.53 (0.34, 0.83) | 0.005 |
Lung vs. Other
| 1.24 (0.76, 2.03) | 0.393 | 1.27 (0.77, 2.09) | 0.353 |
Liver vs. Other
| 1.38 (0.86, 2.22) | 0.188 | 1.44 (0.89, 2.35) | 0.139 |
Type of first and subsequent recurrence by HR
Univariate analysis OR (95% CI) | P-value | Multivariate analysis OR (95% CI) | P-value | |
---|---|---|---|---|
HR-negative vs. positive | HR-negative vs. positive | |||
Local regional
vs.
Distant
| 0.71 (0.44,1.15) | 0.162 | 0.74 (0.44, 1.23) | 0.246 |
Brain vs. Other
| 1.37 (0.93, 2.02) | 0.107 | 1.31 (0.88, 1.95) | 0.191 |
Bone vs. Other
| 0.54 (0.37, 0.78) | 0.001 | 0.55 (0.37, 0.80) | 0.002 |
Lung vs. Other
| 1.48 (1.00, 2.18) | 0.050 | 1.45 (0.98, 2.15) | 0.061 |
Liver vs. Other
| 1.01 (0.69, 1.48) | 0.954 | 1.06 (0.72, 1.56) | 0.764 |
Agreement between primary and metastatic samples
HR status* | HER2* | |||||
---|---|---|---|---|---|---|
ER status | K (ASE) | PR status | K (ASE) | HER2 Status | K (ASE) | |
Total (N)
| 126 | 123 | 121 | |||
Agreement,
N (%)
| ||||||
Yes
| 98 (78) | 0.55 (0.074) | 86 (70) | 0.31 (0.083) | 101 (83) | 0.003 (0.019) |
No
| 28 (22) | 37 (29) | 20 (17) | |||
+ to -
| 18 (14) | 30 (24) | 20 (17) | |||
- to +
| 10 (8) | 7 (6) | N/A |