Introduction
Materials and methods
Study population
Exposure assessment
Outcome assessment
Statistical analyses
Results
Serum 25(OH)D | |||
---|---|---|---|
Characteristic | < 35 nmol/L | 35-55 nmol/L | ≥ 55 nmol/L |
Number of patients | 432 | 407 | 456 |
Age at diagnosis (years), mean ± SD | 64.0 ± 5.7 | 63.7 ± 5.4 | 62.5 ± 5.4 |
25(OH)D concentration (nmol/L), median | 25.7 | 44.4 | 71.3 |
Follow-up time (years), median | 5.6 | 5.9 | 6.0 |
Time between diagnosis and blood collection (days), median | 82 | 63 | 130 |
BMI at recruitment (kg/m2), mean ± SD | 27.7 ± 4.9 | 26.6 ± 4.4 | 25.5 ± 4.1 |
Leisure time physical activity since age 50 (met-hr/wk), mean ± SD | 37.3 ± 30.0 | 43.5 ± 33.0 | 49.5 ± 36.4 |
Season of blood draw, % | |||
Jan-Mar | 37.5 | 16.7 | 13.6 |
Apr-Jun | 22.0 | 24.8 | 16.0 |
Jul-Sept | 13.0 | 29.5 | 43.6 |
Oct-Dec | 27.5 | 29.0 | 26.8 |
Tumor size, % | |||
In situ | 3.9 | 4.9 | 8.3 |
≤ 2 cm | 44.4 | 51.8 | 51.1 |
> 2- ≤ 5 cm | 32.9 | 32.4 | 32.2 |
> 5 cm | 5.6 | 2.2 | 2.6 |
Growth into chest wall/skin | 5.6 | 2.0 | 1.6 |
Neoadjuvant CT | 7.4 | 6.1 | 4.2 |
Missing | 0.2 | 0.5 | 0.0 |
Nodal status, %* | |||
0 | 54.4 | 58.2 | 59.6 |
1-3 | 19.2 | 19.7 | 19.7 |
4-9 | 6.7 | 6.6 | 4.0 |
≥ 10 | 7.6 | 3.7 | 4.2 |
Missing | 0.7 | 0.7 | 0.0 |
Metastases, % | |||
In situ | 3.9 | 4.9 | 8.3 |
No | 89.1 | 89.7 | 88.8 |
Yes | 5.6 | 4.9 | 2.2 |
Missing | 1.4 | 0.5 | 0.7 |
Tumor grade, %* | |||
Low + moderate | 61.1 | 65.1 | 64.5 |
High | 27.3 | 23.3 | 22.8 |
Missing | 0.2 | 0.5 | 0.2 |
ERPR, %* | |||
ER+PR+ | 55.3 | 55.0 | 50.9 |
ER+PR-/ER-PR+ | 19.2 | 15.7 | 20.8 |
ER-PR- | 14.1 | 17.4 | 15.8 |
Missing | 0.0 | 0.7 | 0.0 |
Chemotherapy, % | |||
No | 49.1 | 52.1 | 58.8 |
Yes | 48.8 | 47.6 | 41.0 |
Missing | 2.1 | 0.3 | 0.2 |
Radiotherapy, % | |||
No | 27.8 | 17.9 | 25.4 |
Yes | 72.0 | 82.1 | 74.4 |
Missing | 0.2 | 0.0 | 0.2 |
Tamoxifen/aromatase inhibitor use, % | |||
No | 14.8 | 18.9 | 19.3 |
Yes | 79.9 | 77.2 | 76.3 |
Missing | 5.3 | 3.9 | 4.4 |
Hormone replacement therapy, % | |||
No | 71.1 | 57.7 | 48.9 |
Yes | 27.8 | 41.5 | 50.0 |
Missing | 1.1 | 0.7 | 1.1 |
Diabetes, % | |||
No | 87.0 | 89.7 | 91.9 |
Yes | 13.0 | 10.3 | 7.9 |
Missing | 0.0 | 0.0 | 0.2 |
Cardiovascular disease, % | |||
No | 41.0 | 48.2 | 51.8 |
Yes | 59.0 | 51.8 | 48.2 |
Mode of detection, % | |||
Self-detected by palpation/secretion/pain | 65.3 | 56.3 | 53.5 |
Physician-detected by routine investigation/mammography/ultrasound | 34.5 | 43.5 | 45.4 |
Missing | 0.2 | 0.2 | 1.1 |
Serum 25(OH)D | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Continuous | Categorized | ||||||||||||
per 10 nmol/L decrement | < 35 nmol/L | 35-55 nmol/L | ≥ 55 nmol/L | ||||||||||
Outcome | No. (events) | HR | 95% CI |
P
trend
a
| No. (events) | HR | 95% CI | No. (events) | HR | 95% CI | No. (events) | HR | 95% CI |
Overall mortality | |||||||||||||
Crude†b | 1,295 (183) | 1.11 | 1.03 to 1.18 | 0.009 | 432 (87) | 1.96 | 1.32 to 2.90 | 407 (46) | 0.94 | 0.62 to 1.44 | 456 (50) | 1.00 | - |
Multivariate‡c | 1,265 (174) | 1.08 | 1.00 to 1.17 | 0.07 | 422 (82) | 1.55 | 1.00 to 2.39 | 397 (44) | 0.72 | 0.45 to 1.17 | 446 (48) | 1.00 | - |
Distant disease | |||||||||||||
Crudeb | 1,088 (137) | 1.12 | 1.03 to 1.21 | 0.01 | 341 (64) | 2.09 | 1.31 to 3.30 | 347 (37) | 1.19 | 0.73 to 1.93 | 400 (36) | 1.00 | - |
Multivariatec | 1,074 (135) | 1.14 | 1.05 to 1.24 | 0.006 | 338 (63) | 2.09 | 1.29 to 3.41 | 342 (37) | 1.16 | 0.70 to 1.94 | 394 (35) | 1.00 | - |
Serum 25(OH)D | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Continuous | Categorized | ||||||||||||
per 10 nmol/L decrement | < 35 nmol/L | 35-55 nmol/L | ≥ 55 nmol/L | ||||||||||
Outcome | No. (events) | HR | 95% CI |
P
trend
b
| No. (events) | HR | 95% CI | No. (events) | HR | 95% CI | No. (events) | HR | 95% CI |
Overall mortality | |||||||||||||
All | 1,265 (174) | 1.08 | 1.00 to 1.17 | 0.07 | 422 (82) | 1.55 | 1.00 to 2.39 | 397 (44) | 0.72 | 0.45 to 1.17 | 446 (48) | 1.00 | - |
< 2 years | 1,249 (172) | 1.09 | 1.00 to 1.17 | 0.05 | 418 (82) | 1.57 | 1.01 to 2.43 | 394 (44) | 0.75 | 0.46 to 1.22 | 437 (46) | 1.00 | - |
< 1 year | 1,093 (151) | 1.13 | 1.03 to 1.22 | 0.02 | 375 (77) | 1.81 | 1.11 to 2.94 | 353 (39) | 0.82 | 0.48 to 1.42 | 365 (35) | 1.00 | - |
< 0.5 year | 807 (119) | 1.15 | 1.03 to 1.26 | 0.02 | 277 (63) | 2.19 | 1.21 to 3.97 | 275 (33) | 0.96 | 0.50 to 1.83 | 255 (23) | 1.00 | - |
Distant disease | |||||||||||||
All | 1,074 (135) | 1.14 | 1.05 to 1.24 | 0.006 | 338 (63) | 2.09 | 1.29 to 3.41 | 342 (37) | 1.16 | 0.70 to 1.94 | 394 (35) | 1.00 | - |
< 2 years | 1,059 (133) | 1.15 | 1.05 to 1.25 | 0.005 | 335 (63) | 2.11 | 1.30 to 3.45 | 339 (37) | 1.17 | 0.70 to 1.95 | 385 (33) | 1.00 | - |
< 1 year | 925 (119) | 1.15 | 1.05 to 1.26 | 0.007 | 298 (59) | 2.24 | 1.32 to 3.79 | 302 (32) | 1.28 | 0.74 to 2.22 | 325 (28) | 1.00 | - |
< 0.5 year | 685 (95) | 1.13 | 1.01 to 1.25 | 0.05 | 219 (48) | 2.16 | 1.18 to 3.98 | 235 (25) | 1.12 | 0.60 to 2.10 | 231 (22) | 1.00 | - |
Serum 25(OH)D | |||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Continuous | Categorized | ||||||||||||
per 10 nmol/L decrement | < 35 nmol/L | 35-55 nmol/L | ≥ 55 nmol/L | ||||||||||
Outcome | No. (events) | HR | 95% CI |
P
trend
b
| No. (events) | HR | 95% CI | No. (events) | HR | 95% CI | No. (events) | HR | 95% CI |
Overall mortality | |||||||||||||
All | 1,265 (174) | 1.08 | 1.00 to 1.17 | 0.07 | 422 (82) | 1.55 | 1.00 to 2.39 | 397 (44) | 0.72 | 0.45 to 1.17 | 446 (48) | 1.00 | - |
No/before CTc | 911 (99) | 1.15 | 1.03 to 1.27 | 0.02 | 292 (51) | 2.17 | 1.18 to 3.99 | 276 (20) | 1.00 | 0.51 to 1.96 | 343 (28) | 1.00 | - |
After CTd | 339 (71) | 0.91 | 0.75 to 1.08 | 0.27 | 121 (29) | 0.82 | 0.35 to 1.95 | 117 (22) | 0.59 | 0.24 to 1.44 | 101 (20) | 1.00 | - |
Distant disease | |||||||||||||
All | 1,074 (135) | 1.14 | 1.05 to 1.24 | 0.006 | 338 (63) | 2.09 | 1.29 to 3.41 | 342 (37) | 1.16 | 0.70 to 1.94 | 394 (35) | 1.00 | - |
No/before CTc | 844 (103) | 1.17 | 1.06 to 1.29 | 0.005 | 259 (50) | 2.41 | 1.37 to 4.22 | 263 (26) | 1.07 | 0.59 to 1.94 | 322 (27) | 1.00 | - |
After CTd | 221 (32) | 1.12 | 0.85 to 1.39 | 0.41 | 73 (13) | 1.79 | 0.35 to 9.00 | 78 (11) | 0.84 | 0.14 to 4.97 | 70 (8) | 1.00 | - |
Serum 25(OH)D | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|
Continuous | Categorical | |||||||||
per 10 nmol/L decrement | < 35 nmol/L | 35-55 nmol/L | ≥ 55 nmol/L | |||||||
Variable | Total no. | HR | 95%CI |
P
trend
b
| HR | 95%CI | HR | 95%CI |
P
interaction
c
| |
BMI, kg/m2d | 0.74 | |||||||||
< 26 | 382 | 1.05 | 0.66 to 1.44 | 0.81 | 0.64 | 0.08 to 5.00 | 0.02 | 0.00 to 2.06 | Referent | |
≥ 26 | 393 | 1.15 | 0.94 to 1.36 | 0.20 | 2.57 | 0.88 to 7.54 | 0.60 | 0.19 to 1.92 | Referent | |
Leisure time physical activity, MET-h/wk | 0.49 | |||||||||
< 37 | 631 | 1.04 | 0.92 to 1.17 | 0.50 | 1.19 | 0.62 to 2.29 | 0.63 | 0.30 to 1.32 | Referent | |
≥ 37 | 629 | 1.19 | 1.03 to 1.35 | 0.03 | 1.90 | 0.85 to 4.24 | 0.57 | 0.22 to 1.48 | Referent | |
HRT use | 0.40 | |||||||||
Never, past | 746 | 1.13 | 1.01 to 1.25 | 0.04 | 1.89 | 1.09 to 3.26 | 0.61 | 0.31 to 1.19 | Referent | |
Current | 506 | 1.03 | 0.86 to 1.21 | 0.73 | 0.89 | 0.26 to 3.05 | 1.17 | 0.46 to 2.98 | Referent | |
ER status | 0.78 | |||||||||
ER+ | 903 | 1.08 | 0.97 to 1.19 | 0.17 | 1.70 | 0.95 to 3.05 | 0.72 | 0.39 to 1.35 | Referent | |
ER- | 276 | 1.09 | 0.84 to 1.35 | 0.50 | 1.48 | 0.38 to 5.76 | 0.81 | 0.21 to 3.09 | Referent |