Background
Methods
The Danish nurse cohort
Active tobacco smoking
Breast cancer definition
Statistical analyses
Results
Total
N = 21,831 | Breast Cancer
N = 1162 | No Breast Cancer
N = 20,669 | |
---|---|---|---|
Age | |||
Mean (SD) age at baseline (years) | 53.2 (8.0) | 53.7 (7.6) | 53.2 (8.1) |
Birth Cohort | |||
Born 1900–1934, n (%) | 5179 (23.7) | 295 (25.4) | 4884 (23.6) |
Born 1935–1944, n (%) | 6707 (30.7) | 428 (36.8) | 6279 (30.4) |
Born 1945–1949, n (%) | 4564 (20.9) | 244 (21.0) | 4320 (20.9) |
Born 1950–1955, n (%) | 5381 (24.6) | 195 (16.8) | 5186 (25.1) |
Reproductive Factors | |||
Mean (SD) age at menarche | 13.5 (1.5) | 13.5 (1.5) | 13.5 (1.5) |
Nulliparous, n (%) | 3170 (14.5) | 189 (16.3) | 2981 (14.4) |
Mean (SD) number of children in parous women | 2.3 (0.9) | 2.3 (0.9) | 2.3 (0.9) |
Mean (SD) age at first birth in parous women | 25.9 (4.0) | 25.9 (4.0) | 26.3 (4.1) |
Postmenopausal, n (%) | 12,376 (56.7) | 696 (59.9) | 11,680 (56.5) |
Body Mass Index (BMI) | |||
Mean (SD) BMI (kg/m2) | 23.7 (3.5) | 23.8 (3.5) | 23.7 (3.5) |
BMI < 18.5 kg/m2, n (%) | 529 (2.4) | 22 (1.9) | 507 (2.5) |
BMI 18.5–24.9 kg/m2, n (%) | 15,070 (69.0) | 819 (70.5) | 14,251 (68.9) |
BMI 25–29.9 kg/m2, n (%) | 4979 (22.8) | 245 (21.1) | 4734 (22.9) |
BMI ≥ 30 kg/m2, n (%) | 1253 (5.7) | 76 (6.5) | 1177 (5.7) |
Alcohol consumption | |||
Does not drink alcohol, n (%) | 3320 (15.2) | 183 (15.7) | 3137 (15.2) |
Moderate drinker (1–14 drinks/week), n (%) | 13,533 (62.0) | 670 (57.7) | 12,863 (62.2) |
Heavy drinker (> 14 drinks/week), n (%) | 4978 (22.8) | 309 (26.6) | 4669 (22.6) |
Leisure time physical activity | |||
Low physical activity, n (%) | 1428 (6.5) | 79 (6.8) | 1349 (6.5) |
Medium physical activity, n (%) | 5905 (27.0) | 298 (25.6) | 5607 (27.1) |
High physical activity, n (%) | 14,498 (66.4) | 785 (67.6) | 13,713 (66.3) |
Shift Work | |||
Working night shifts, n (%) | 967 (5.5) | 45 (4.9) | 922 (5.5) |
Hormone Use | |||
Ever used oral contraceptives, n (%) | 12,701 (58.2) | 663 (57.1) | 12,038 (58.2) |
Ever used hormone therapy, n (%) | 5951 (27.3) | 407 (35.0) | 5544 (26.8) |
Smoking Status | |||
Never smoker, n (%) | 7923 (36.3) | 379 (32.6) | 7544 (36.5) |
Former smoker, n (%) | 6557 (30.0) | 338 (29.1) | 6219 (30.1) |
Current smoker, n (%) | 7351 (33.7) | 445 (38.3) | 6906 (33.4) |
Ever smoker, n (%) | 13,908 (63.7) | 783 (67.4) | 13,125 (63.5) |
Smoking Intensity | |||
Mean (SD) smoking durationa (years) | 23.3 (12.2) | 23.9 (11.7) | 23.3 (12.2) |
Mean (SD) smoking intensitya (g/day) | 12.4 (8.3) | 12.7 (8.0) | 12.4 (8.3) |
Mean (SD) pack-yearsa
| 16.0 (14.8) | 16.6 (14.8) | 15.9 (14.8) |
Initiation of smoking | |||
Mean age (SD) at smoking initiationa (years) | 20.4 (5.5) | 20.7 (5.7) | 20.4 (5.5) |
Initiation of smoking in 18,661 parous women | |||
Parous never smoker | 6938 (37.2) | 326 (33.5) | 6612 (37.4) |
Parous ever smoker | 11,723 (62.8) | 647 (66.5) | 11,076 (62.6) |
Parous/around 1st birth or later, n (%) | 1457 (6.7) | 88 (7.6) | 1369 (6.6) |
Parous/before 1st childbirth, ≤ 10 pack-years, n (%) | 9367 (42.9) | 493 (42.4) | 8874 (42.9) |
Parous/before 1st childbirth, > 10 pack-years, n (%) | 899 (4.1) | 66 (5.7) | 833 (4.0) |
Initiation of smoking in 3170 nulliparous women | |||
Nulliparous never smoker | 985 (31.1) | 53 (28.0) | 932 (31.3) |
Nulliparous ever smoker | 2185 (68.9) | 136 (72.0) | 2049 (68.7) |
Nulliparous, before age 21b years, n (%) | 1264 (5.8) | 74 (6.4) | 1190 (5.8) |
Nulliparous, age 21 years or later, n (%) | 921 (4.2) | 62 (5.3) | 859 (4.2) |
Initiation of smoking in 12,376 postmenopausal women | |||
Postmenopausal never smoker, n (%) | 3988 (32.2) | 202 (29.0) | 3786 (32.4) |
Before menopause, n (%) | 8301 (67.1) | 488 (70.1) | 7813 (66.9) |
After menopause, n (%) | 87 (0.7) | 6 (0.9) | 81 (0.7) |
Birth Cohort | 1900–1934
N = 5179 | 1935–1944
N = 6707 | 1945–1949
N = 4564 | 1950–1955
N = 5381 |
---|---|---|---|---|
Age | ||||
Mean (SD) age at baseline (years) | 65.3 (5.8) | 53.1 (3.0) | 47.7 (1.9) | 46.4 (1.5) |
Reproductive Factors | ||||
Mean (SD) age at menarche | 14.0 (1.5) | 13.6 (1.6) | 13.4 (1.5) | 13.2 (1.5) |
Nulliparous, n (%) | 1401 (27.1) | 764 (11.4) | 431 (9.4) | 574 (10.7) |
Mean (SD) number of children in parous women | 2.5 (1.0) | 2.4 (0.9) | 2.3 (0.8) | 2.3 (0.8) |
Mean (SD) age at first birth in parous women | 27.9 (4.1) | 25.7 (3.6) | 25.0 (3.6) | 25.6 (4.2) |
Postmenopausal, n (%) | 5170 (99.8) | 5060 (75.4) | 1240 (27.2) | 906 (16.8) |
Body Mass Index (BMI) | ||||
Mean (SD) BMI (kg/m2) | 23.8 (3.5) | 23.7 (3.4) | 23.5 (3.4) | 23.8 (3.6) |
BMI < 18.5 kg/m2, n (%) | 199 (3.8) | 148 (2.2) | 100 (2.2) | 82 (1.5) |
BMI 18.5–24.9 kg/m2, n (%) | 3368 (65.0) | 4657 (69.4) | 3293 (72.2) | 3752 (69.7) |
BMI 25–29.9 kg/m2, n (%) | 1315 (25.4) | 1527 (22.8) | 944 (20.7) | 1193 (22.2) |
BMI ≥ 30 kg/m2, n (%) | 297 (5.7) | 375 (5.6) | 227 (5.0) | 354 (6.6) |
Alcohol consumption | ||||
Does not drink alcohol, n (%) | 1278 (24.7) | 980 (14.6) | 516 (11.3) | 546 (10.1) |
Moderate drinker (1–14 drinks/week), n (%) | 2900 (56.0) | 4177 (62.3) | 2923 (64.0) | 3533 (65.7) |
Heavy drinker (> 14 drinks/week), n (%) | 1001 (19.3) | 1550 (23.1) | 1125 (24.6) | 1302 (24.2) |
Leisure time physical activity | ||||
Low physical activity, n (%) | 467 (9.0) | 392 (5.8) | 250 (5.5) | 319 (5.9) |
Medium physical activity, n (%) | 1090 (21.0) | 1809 (27.0) | 1406 (30.8) | 1600 (29.7) |
High physical activity, n (%) | 3622 (69.9) | 4506 (67.2) | 2908 (63.7) | 3462 (64.3) |
Shift Work | ||||
Working night shifts, n (%) | 191 (12.5) | 453 (7.4) | 178 (4.0) | 145 (2.7) |
Hormone Use | ||||
Ever used oral contraceptives, n (%) | 2082 (40.2) | 2490 (37.1) | 779 (17.1) | 600 (11.2) |
Ever used hormone therapy, n (%) | 1143 (22.1) | 3544 (52.8) | 3462 (75.9) | 4552 (84.6) |
Smoking status | ||||
Never smoker, n (%) | 1481 (28.6) | 2487 (37.1) | 1840 (40.3) | 2115 (39.3) |
Former smoker, n (%) | 1812 (35.0) | 1716 (25.6) | 1242 (27.2) | 1787 (33.2) |
Current smoker, n (%) | 1886 (36.4) | 2504 (37.3) | 1482 (32.5) | 1479 (27.5) |
Ever smoker, n (%) | 3698 (71.4) | 4220 (62.9) | 2724 (59.7) | 3266 (60.7) |
Smoking Intensity | ||||
Mean (SD) smoking durationa (years) | 29.4 (14.5) | 23.4 (11.3) | 19.8 (9.5) | 19.4 (9.2) |
Mean (SD) smoking intensitya (g/day) | 12.1 (9.0) | 13.0 (8.8) | 12.5 (7.5) | 12.0 (7.5) |
Mean (SD) pack-yearsa
| 19.5 (18.6) | 16.9 (14.9) | 13.5 (11.1) | 12.8 (11.0) |
Initiation of smoking | ||||
Mean age (SD) at smoking initiationa (years) | 22.6 (6.9) | 21.1 (5.3) | 19.6 (3.9) | 17.8 (3.3) |
Initiation of smoking in 18,661 parous women | ||||
Parous never smoker, n (%) | 1078 (28.5) | 2246 (37.8) | 1684 (40.8) | 1930 (40.2) |
Parous ever smoker, n (%) | 2700 (71.5) | 3697 (62.2) | 2449 (59.3) | 2877 (59.9) |
Parous/around 1st birth or later, n (%) | 430 (8.3) | 632 (9.4) | 259 (5.7) | 136 (2.5) |
Parous/before 1st childbirth, ≤ 10 pack-years, n (%) | 2047 (39.5) | 2824 (42.1) | 2037 (44.6) | 2459 (45.7) |
Parous/before 1st childbirth, > 10 pack-years, n (%) | 223 (4.3) | 241 (3.6) | 153 (3.4) | 282 (5.2) |
Initiation of smoking in 3170 nulliparous women | ||||
Nulliparous never smoker, n (%) | 403 (28.8) | 241 (31.5) | 156 (36.2) | 185 (32.2) |
Nulliparous ever smoker, n (%) | 998 (71.2) | 523 (68.5) | 275 (63.8) | 389 (67.8) |
Nulliparous, before age 21b years, n (%) | 442 (8.5) | 295 (4.4) | 187 (4.1) | 340 (6.3) |
Nulliparous, age 21 years or later, n (%) | 556 (10.7) | 228 (3.4) | 88 (1.9) | 49 (0.9) |
Initiation of smoking in 12,376 postmenopausal women | ||||
Postmenopausal never smoker, n (%) | 1477 (28.6) | 1757 (34.7) | 454 (36.6) | 300 (33.1) |
Postmenopausal ever smoker, n (%) | 3693 (71.4) | 3303 (65.3) | 786 (63.4) | 606 (66.9) |
Before menopause, n (%) | 3633 (70.3) | 3281 (64.8) | 782 (63.1) | 605 (66.8) |
After menopause, n (%) | 60 (1.2) | 22 (0.4) | 4 (0.3) | 1 (0.1) |
N
| Person-years | No. of cases | Age adjusted | Fullya adjusted | |
---|---|---|---|---|---|
HR (95% CI) | HR (95% CI) | ||||
Never smoked (ref.) | 7923 | 126,950 | 379 | 1.00 | 1.00 |
Former smoker | 6557 | 102,190 | 338 | 1.11 (0.96–1.29) | 1.08 (0.94–1.26) |
Current smoker | 7351 | 113,400 | 445 | 1.32 (1.15–1.51) | 1.27 (1.11–1.46) |
Ever smokers | 13,908 | 215,589 | 783 | 1.22 (1.08–1.38) | 1.18 (1.04–1.34) |
Smoking duration among ever smokers | |||||
≤ 10 years | 2925 | 47,335 | 156 | 1.10 (0.92–1.33) | 1.10 (0.91–1.33) |
11–20 years | 3175 | 50,151 | 175 | 1.17 (0.98–1,40) | 1.15 (0.96–1.38) |
21–30 years | 4456 | 68,818 | 259 | 1.26 (1.08–1.48) | 1.24 (1.06–1.46) |
> 30 years | 3295 | 49,285 | 193 | 1.32 (1.11–1.57) | 1.21 (1.01–1.46) |
p-value for trend
|
0.004
| ||||
Every increase of 10 years | 1.08 (1.04–1.12) | 1.06 (1.02–1-11) | |||
Smoking (Tobacco) Intensity among ever smokers | |||||
> 6 g/day | 3098 | 49,245 | 161 | 1.10 (0.91–1.32) | 1.07 (0.89–1.29) |
6–10 g/day | 4317 | 67,410 | 235 | 1.17 (0.99–1.38) | 1.14 (0.97–1.34) |
11–15 g/day | 3050 | 46,962 | 175 | 1.25 (1.05–1.50) | 1.22 (1.02–1.46) |
> 15 g/day | 3443 | 51,973 | 212 | 1.37 (1.16–1.62) | 1.31 (1.11–1.56) |
p-value for trend
|
0.001
| ||||
Every increase of 10 g/day | 1.05 (0.97–1.14) | 1.04 (0.95–1.13) | |||
Lifetime pack-years | |||||
≤ 10 pack-years | 6082 | 96,640 | 327 | 1.13 (0.98–1.31) | 1.12 (0.97–1.30) |
11–20 pack-years | 3536 | 54,993 | 192 | 1.17 (0.99–1.39) | 1.14 (0.96–1.36) |
> 20 pack-years | 4290 | 63,956 | 264 | 1.39 (1.19–1.63) | 1.32 (1.12–1.55) |
p-value for trend
|
0.002
| ||||
Every increase of 20 pack-years | 1.10 (1.01–1.20) | 1.07 (0.98–1.18) | |||
Initiation of smoking in 18,661 parous women | |||||
Parous never smoker (ref.) | 6938 | 111,811 | 326 | 1.00 | 1.00 |
Parous, around first birth or later | 1457 | 23,553 | 88 | 1.28 (1.01–1.62) | 1.28 (1.00–1.62) |
Parous, before first childbirth, ≤ 10 pack-years | 9367 | 146,965 | 493 | 1.15 (1.00–1.33) | 1.13 (0.98–1.31) |
Parous, before first childbirth, > 10 pack-years | 899 | 12,901 | 66 | 1.77 (1.36–2-31) | 1.58 (1.20–2.10) |
Initiation of smoking in 3170 nulliparous women | |||||
Nulliparous never smoker (ref.) | 985 | 15,138 | 53 | 1.00 | 1.00 |
Nulliparous, before age 21b years | 1264 | 18,737 | 74 | 1.14 (0.80–1.62) | 1.10 (0.76–1.58) |
Nulliparous, age 21 years or later | 921 | 13,434 | 62 | 1.31 (0.91–1.90) | 1.29 (0.89–1.88) |
Initiation of smoking in 12,376 postmenopausal women | |||||
Postmenopausal never smoker (ref.) | 3988 | 66,617 | 202 | 1.00 | 1.00 |
Before menopause | 8301 | 130,987 | 488 | 1.23 (1.05–1.45) | 1.20 (1.01–1.41) |
After menopause | 87 | 1252 | 6 | 1.60 (0.71–3.59) | 1.66 (0.74–3.75) |
Pack-years in 8347 parous postmenopausal womenc
| |||||
Parous postmenopausal never smoker (ref.) | 2712 | 129 | 1.00 | 1.00 | |
Pack-years before 1st childbirthd
| |||||
≤ 10 pack-years | 4349 | 70,627 | 227 | 1.16 (0.93–1.44) | 1.14 (0.92–1.42) |
11–20 pack-years | 366 | 5233 | 34 | 2.36 (1.62–3.45) | 2.16 (1.45–3.20) |
> 20 pack-years | 61 | 854 | 4 | 1.69 (0.63–4.59) | 1.38 (0.50–3.78) |
p-value for trend
|
0.006
| ||||
Pack-years from 1st childbirth until menopaused
| |||||
≤ 10 pack-years | 2572 | 42,484 | 128 | 1.08 (0.85–1.38) | 1.03 (0.81–1.33) |
11–20 pack-years | 1606 | 25,391 | 79 | 1.12 (0.85–1.49) | 1.13 (0.85–1.50) |
> 20 pack-years | 817 | 12,471 | 60 | 1.74 (1.28–2.36) | 1.84 (1.34–2.53) |
p-value for trend
|
0.029
| ||||
Pack-years after menopaused
| |||||
≤ 10 pack-years | 2294 | 37,270 | 124 | 1.20 (0.94–1.53) | 1.19 (0.93–1.53) |
11–20 pack-years | 453 | 6695 | 20 | 1.09 (0.68–1.74) | 1.03 (0.64–1.66) |
> 20 pack-years | 1966 | 32,094 | 118 | 1.32 (1.03–1.70) | 1.29 (0.70–4.98) |
p-value for trend
|
0.412
|
Never | Former | Current | Ever | |||
---|---|---|---|---|---|---|
N
| No. of cases | HR (95% CI) | HR (95% CI) | HR (95% CI) | HR (95% CI) | |
Menopausal status | ||||||
Premenopausal | 9455 | 466 | 1.00 | 1.03 (0.82–1.29) | 1.30 (1.04–1.61) | 1.16 (0.95–1.40) |
Postmenopausal | 12,376 | 696 | 1.00 | 1.12 (1.92–1.37) | 1.27 (1.05–1.52) | 1.20 (1.02–1.42) |
p-value
|
0.77
|
0.80
| ||||
BMI | ||||||
Not obese (< 30 kg/m2) | 20,578 | 1086 | 1.00 | 1.07 (0.92–1.25) | 1.25 (1.08–1.45) | 1.11 (1.03–1.33) |
Obese (≥ 30 kg/m2) | 1253 | 76 | 1.00 | 1.23 (0.72–2.09) | 1.47 (0.81–2.66) | 1.32 (0.82–2.12) |
p-value
|
0.84
|
0.63
| ||||
Alcohol Consumption | ||||||
None | 3320 | 183 | 1.00 | 1.11 (0.77–1.61) | 1.17 (0.83–1.66) | 1.14 (0.85–1.54) |
Moderate (1–14 drinks/week) | 13,533 | 670 | 1.00 | 1.13 (0.94–1.37) | 1.26 (1.05–1.52) | 1.19 (1.02–1.40) |
Heavy (>14 drinks/week) | 4978 | 309 | 1.00 | 0.96 (0.70–1.31) | 1.34 (1.01–1.77) | 1.17 (0.90–1.52) |
p-value
|
0.66
|
0.99
| ||||
Hormone therapy use | ||||||
Never | 15,880 | 755 | 1.00 | 1.05 (0.88–1.26) | 1.21 (1.02–1.44) | 1.13 (0.97–1.32) |
Ever | 5951 | 407 | 1.00 | 1.15 (0.88–1.49) | 1.36 (1.06–1.73) | 1 26 (1.01–1.58) |
p-value
|
0.63
|
0 33
|
Never | Former | Current | Ever | ||
---|---|---|---|---|---|
N
| Ref. | HR (95% CI) | HR (95% CI) | HR (95% CI) | |
Estrogen Receptor (ER) Status | |||||
ER + | 851 | 1.00 | 1.06 (0.89–1.26) | 1.28 (1.09–1.51) | 1.17 (1.01–1.36) |
ER - | 172 | 1.00 | 1.11 (0.77–1.62) | 1.11 (0.77–1.61) | 1.11 (0.81–1.53) |
Receptor Status | |||||
ER+/PR+ | 366 | 1.00 | 1.17 (0.90–1.53) | 1.36 (1.06–1.76) | 1.27 (1.02–1.59) |
ER+/PR- | 111 | 1.00 | 1.56 (0.94–2.59) | 1.92 (1.19–3.10) | 1.75 (1.12–2.71) |
ER−/PR- | 107 | 1.00 | 1.01 (0.63–1.63) | 1.15 (0.73–1.82) | 1.08 (0.72–1.61) |
ER−/PR+ | 10 | 1.00 | 1.76 (0.41–7.56) | 0.49 (0.08–3.01) | 1.02 (0.26–4.07) |