Characteristics | Luminal A-like: ER+ PR+ HER2-, low and medium grade | Luminal B-like, HER2-negative: ER+ PR- HER2-, high grade | Luminal B-like, HER2 positive: ER+ PR+/PR- HER2+, low/medium/high grade | HER2-positive: ER- PR- HER2+ | Triple-negative: ER- PR- HER2- | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Controls (n) | Cases (n) | OR* | 95% CI | Controls (n) | Cases (n) | OR | 95% CI | Controls (n) | Cases (n) | OR | 95%CI | Controls (n) | Cases (n) | OR | 95% CI | Controls (n) | Cases (n) | OR | 95% CI | |
Age at first birth (years) | ||||||||||||||||||||
13–20 | 3951 | 609 | 1 | Reference | 1001 | 42 | 1 | Reference | 553 | 91 | 1 | Reference | 279 | 54 | 1 | Reference | 495 | 95 | 1 | Reference |
21–22 | 2277 | 376 | 1.06 | (0.91, 1.23) | 620 | 32 | 1.31 | (0.77, 2.25) | 305 | 47 | 0.94 | (0.62, 1.42) | 170 | 32 | 0.90 | (0.53, 1.53) | 326 | 65 | 1.13 | (0.78, 1.62) |
23–25 | 3152 | 481 | 0.99 | (0.86, 1.14) | 759 | 32 | 1.42 | (0.80, 2.52) | 437 | 87 | 1.21 | (0.85, 1.73) | 222 | 36 | 0.72 | (0.43, 1.20) | 393 | 86 | 1.28 | (0.89, 1.85) |
26–30 | 2473 | 427 | 1.12 | (0.96, 1.30) | 647 | 25 | 0.71 | (0.38, 1.31) | 343 | 59 | 1.16 | (0.78, 1.74) | 216 | 41 | 0.94 | (0.56, 1.55) | 318 | 63 | 1.13 | (0.76, 1.67) |
31–50 | 937 | 196 | 1.27 | (1.03, 1.57) | 223 | 15 | 1.28 | (0.58, 2.81) | 127 | 32 | 1.53 | (0.90, 2.60) | 63 | 23 | 1.65 | (0.86, 3.17) | 120 | 29 | 1.36 | (0.80, 2.33) |
p-trend* | 0.06 | 0.82 | 0.12 | 0.53 | 0.28 | |||||||||||||||
p-heterogeneity# | 0.73 | 0.24 | 0.71 | 0.72 | ||||||||||||||||
Number of pregnancies lasting 6+ months | ||||||||||||||||||||
0 | 1199 | 245 | 1 | Reference | 303 | 15 | 1 | Reference | 164 | 43 | 1 | Reference | 84 | 27 | 1 | Reference | 144 | 34 | 1 | Reference |
1 | 1596 | 325 | 0.95 | (0.78, 1.15) | 426 | 18 | 0.90 | (0.42, 1.94) | 229 | 41 | 0.58 | (0.35, 0.96) | 128 | 20 | 0.50 | (0.26, 0.96) | 224 | 41 | 0.70 | (0.42, 1.16) |
2 | 6266 | 1057 | 0.80 | (0.68, 0.94) | 1602 | 75 | 1.03 | (0.55, 1.94) | 842 | 178 | 0.78 | (0.52, 1.16) | 426 | 97 | 0.78 | (0.47, 1.29) | 813 | 158 | 0.77 | (0.50, 1.18) |
3 | 3883 | 572 | 0.67 | (0.56, 0.79) | 950 | 42 | 0.93 | (0.47, 1.82) | 528 | 81 | 0.56 | (0.36, 0.86) | 319 | 60 | 0.61 | (0.36, 1.03) | 477 | 117 | 0.98 | (0.63, 1.53) |
>4 | 1518 | 199 | 0.62 | (0.50, 0.77) | 383 | 13 | 0.82 | (0.36, 1.87) | 225 | 28 | 0.43 | (0.25, 0.73) | 98 | 19 | 0.60 | (0.31, 1.19) | 196 | 36 | 0.70 | (0.41, 1.21) |
p-trend | <0.0001 | 0.66 | 0.002 | 0.19 | 0.88 | |||||||||||||||
p-heterogeneity | 0.85 | 0.41 | 0.31 | 0.04 | ||||||||||||||||
Parous women only | ||||||||||||||||||||
Duration breastfeeding (months) | ||||||||||||||||||||
No breastfeeding | 997 | 165 | 1 | Reference | 260 | 10 | 1 | Reference | 146 | 31 | 1 | Reference | 78 | 10 | 1 | Reference | 135 | 24 | 1 | Reference |
0–6 | 3145 | 500 | 0.93 | (0.76, 1.15) | 831 | 37 | 0.95 | (0.41, 2.18) | 449 | 71 | 0.67 | (0.40, 1.10) | 243 | 37 | 1.42 | (0.63, 3.18) | 467 | 80 | 1.01 | (0.60, 1.71) |
7–12 | 3108 | 527 | 1.07 | (0.87, 1.31) | 763 | 38 | 0.94 | (0.41, 2.19) | 427 | 91 | 0.84 | (0.51, 1.37) | 215 | 52 | 2.25 | (1.02, 4.99) | 359 | 95 | 1.65 | (0.98, 2.78) |
13–20 | 2583 | 402 | 0.99 | (0.80, 1.24) | 654 | 32 | 0.91 | (0.38, 2.18) | 343 | 75 | 0.94 | (0.56, 1.58) | 156 | 48 | 2.51 | (1.11, 5.68) | 308 | 69 | 1.29 | (0.74, 2.23) |
21–30 | 1700 | 263 | 1.02 | (0.80, 1.30) | 399 | 13 | 0.46 | (0.17, 1.21) | 240 | 37 | 0.67 | (0.36, 1.24) | 147 | 28 | 1.78 | (0.74, 4.28) | 222 | 44 | 1.18 | (0.65, 2.15) |
>30 | 966 | 154 | 1.11 | (0.83, 1.47) | 250 | 9 | 0.81 | (0.26, 2.53) | 121 | 12 | 0.57 | (0.25, 1.29) | 70 | 13 | 1.82 | (0.67, 4.97) | 123 | 24 | 1.19 | (0.58, 2.44) |
p-trend | 0.33 | 0.17 | 0.69 | 0.12 | 0.52 | |||||||||||||||
p-heterogeneity | 0.72 | 0.16 | 0.60 | 0.85 | ||||||||||||||||
Menopausal status | ||||||||||||||||||||
Premenopausal | 1171 | 291 | 1 | Reference | 208 | 10 | 1 | Reference | 173 | 30 | 1 | Reference | 100 | 18 | 1 | Reference | 130 | 29 | 1 | Reference |
Perimenopausal | 1055 | 175 | 0.59 | (0.47, 0.74) | 225 | 11 | 0.91 | (0.34, 2.42) | 152 | 25 | 0.82 | (0.44, 1.50) | 79 | 20 | 1.41 | (0.67, 2.94) | 143 | 37 | 1.13 | (0.64, 1.99) |
Postmenopausal | 12000 | 1932 | 0.50 | (0.42, 0.60) | 3231 | 142 | 1.06 | (0.47, 2.39) | 1663 | 316 | 1.05 | (0.64, 1.72) | 876 | 185 | 1.21 | (0.66, 2.23) | 1581 | 320 | 0.82 | (0.50, 1.33) |
p-trend | <0.0001 | 0.77 | 0.59 | 0.71 | 0.21 | |||||||||||||||
p-heterogeneity | 0.02 | 0.01 | 0.001 | 0.002 | ||||||||||||||||
Age of menopause (years) | ||||||||||||||||||||
<47 | 2569 | 367 | 1 | Reference | 640 | 24 | 1 | Reference | 334 | 44 | 1 | Reference | 204 | 22 | 1 | Reference | 336 | 61 | 1 | Reference |
47–49 | 2404 | 373 | 1.11 | (0.94, 1.31) | 639 | 32 | 1.21 | (0.65, 2.27) | 326 | 55 | 1.34 | (0.85, 2.10) | 181 | 39 | 2.06 | (1.14, 3.73) | 292 | 72 | 1.47 | (0.98, 2.20) |
50–52 | 4698 | 704 | 1.11 | (0.96, 1.29) | 1190 | 51 | 1.33 | (0.76, 2.31) | 663 | 123 | 1.57 | (1.06, 2.33) | 338 | 77 | 2.32 | (1.36, 3.94) | 623 | 102 | 0.99 | (0.69, 1.44) |
>52 | 3255 | 491 | 1.05 | (0.90, 1.23) | 871 | 35 | 1.29 | (0.71, 2.34) | 442 | 90 | 1.71 | (1.12, 2.61) | 225 | 48 | 2.38 | (1.33, 4.26) | 420 | 88 | 1.37 | (0.94, 2.01) |
p-trend | 0.60 | 0.37 | 0.01 | 0.004 | 0.42 | |||||||||||||||
p-heterogeneity | 0.84 | 0.03 | 0.06 | 0.26 | ||||||||||||||||
Age at start of oral contraceptives (years) | ||||||||||||||||||||
Never used | 6715 | 1070 | 1 | Reference | 1758 | 78 | 1 | Reference | 876 | 166 | 1 | Reference | 501 | 115 | 1 | Reference | 860 | 165 | 1 | Reference |
14–18 | 1476 | 226 | 0.94 | (0.79, 1.12) | 334 | 12 | 0.72 | (0.34, 1.50) | 187 | 44 | 1.24 | (0.80, 1.92) | 128 | 17 | 0.49 | (0.26, 0.93) | 180 | 55 | 1.86 | (1.23, 2.81) |
19–20 | 1462 | 319 | 1.33 | (1.14, 1.55) | 367 | 23 | 1.35 | (0.76, 2.39) | 230 | 47 | 1.09 | (0.72, 1.63) | 133 | 27 | 0.74 | (0.45, 1.23) | 206 | 46 | 1.24 | (0.83, 1.85) |
21–24 | 1959 | 323 | 1.02 | (0.88, 1.18) | 458 | 23 | 1.14 | (0.65, 2.00) | 295 | 43 | 0.78 | (0.53, 1.15) | 130 | 24 | 0.71 | (0.42, 1.18) | 253 | 41 | 0.82 | (0.55, 1.22) |
25–50 | 1993 | 325 | 1.01 | (0.87, 1.16) | 536 | 18 | 0.71 | (0.40, 1.25) | 296 | 54 | 1.01 | (0.70, 1.44) | 114 | 27 | 1.09 | (0.66, 1.79) | 258 | 58 | 1.17 | (0.82, 1.67) |
p-trend | 0.41 | 0.63 | 0.56 | 0.70 | 0.91 | |||||||||||||||
p-heterogeneity | 0.77 | 0.54 | 0.08 | 0.02 | ||||||||||||||||
Duration of oral contraceptives (years) | ||||||||||||||||||||
Never used | 6715 | 1070 | 1 | Reference | 1758 | 78 | 1 | Reference | 876 | 166 | 1 | Reference | 501 | 115 | 1 | Reference | 860 | 165 | 1 | Reference |
<2 | 1839 | 294 | 0.97 | (0.84, 1.13) | 482 | 19 | 0.75 | (0.42, 1.34) | 275 | 33 | 0.67 | (0.44, 1.03) | 151 | 18 | 0.47 | (0.27, 0.81) | 263 | 43 | 0.85 | (0.58, 1.26) |
2–5 years | 1753 | 295 | 1.05 | (0.91, 1.23) | 435 | 15 | 0.73 | (0.39, 1.38) | 233 | 46 | 0.95 | (0.64, 1.41) | 113 | 17 | 0.61 | (0.34, 1.09) | 228 | 56 | 1.32 | (0.92, 1.89) |
5–10 years | 1568 | 268 | 1.06 | (0.90, 1.24) | 388 | 20 | 1.02 | (0.56, 1.85) | 240 | 54 | 1.27 | (0.87, 1.85) | 121 | 35 | 1.07 | (0.66, 1.73) | 203 | 47 | 1.20 | (0.82, 1.76) |
>10 years | 1266 | 232 | 1.09 | (0.92, 1.29) | 271 | 14 | 1.00 | (0.49, 2.03) | 204 | 41 | 0.95 | (0.62, 1.44) | 82 | 19 | 1.02 | (0.56, 1.86) | 149 | 38 | 1.25 | (0.82, 1.90) |
p-trend | 0.22 | 0.91 | 0.54 | 0.91 | 0.11 | |||||||||||||||
p-heterogeneity | 0.76 | 0.14 | 0.003 | 0.66 | ||||||||||||||||
Age at start of intrauterine device (years) | ||||||||||||||||||||
Never users | 10000 | 1609 | 1 | Reference | 2600 | 113 | 1 | Reference | 1368 | 266 | 1 | Reference | 729 | 153 | 1 | Reference | 1279 | 267 | 1 | Reference |
14–28 | 612 | 105 | 1.12 | (0.89, 1.41) | 152 | 5 | 1.14 | (0.40, 3.24) | 82 | 14 | 0.76 | (0.40, 1.45) | 55 | 12 | 0.91 | (0.46, 1.80) | 88 | 19 | 1.07 | (0.62, 1.83) |
29–35 | 681 | 113 | 0.99 | (0.79, 1.23) | 152 | 7 | 1.11 | (0.45, 2.72) | 93 | 10 | 0.62 | (0.31, 1.24) | 46 | 7 | 0.68 | (0.27, 1.68) | 78 | 25 | 1.51 | (0.90, 2.55) |
36–42 | 532 | 121 | 1.57 | (1.25, 1.98) | 114 | 5 | 0.61 | (0.22, 1.72) | 89 | 18 | 0.95 | (0.54, 1.69) | 43 | 7 | 0.69 | (0.29, 1.61) | 78 | 12 | 0.75 | (0.39, 1.44) |
43–50 | 456 | 96 | 1.32 | (1.02, 1.69) | 136 | 5 | 0.97 | (0.33, 2.86) | 70 | 8 | 0.57 | (0.25, 1.28) | 39 | 7 | 0.85 | (0.35, 2.09) | 70 | 14 | 1.01 | (0.53, 1.90) |
p-trend | 0 | 0.66 | 0.13 | 0.31 | 0.89 | |||||||||||||||
p-heterogeneity | 0.79 | 0.07 | 0.21 | 0.40 | ||||||||||||||||
Duration of intrauterine device (years) | ||||||||||||||||||||
Never used | 10000 | 1609 | 1 | Reference | 2600 | 113 | 1 | Reference | 1368 | 266 | 1 | Reference | 729 | 153 | 1 | Reference | 1279 | 267 | 1 | Reference |
<2 | 341 | 53 | 0.96 | (0.70, 1.32) | 83 | 2 | 0.81 | (0.16, 4.02) | 56 | 12 | 1.17 | (0.58, 2.39) | 33 | 5 | 0.84 | (0.31, 2.32) | 37 | 7 | 0.90 | (0.38, 2.13) |
2–5 years | 432 | 89 | 1.27 | (0.98, 1.63) | 112 | 6 | 1.79 | (0.62, 5.18) | 62 | 10 | 0.85 | (0.41, 1.76) | 36 | 7 | 0.81 | (0.34, 1.91) | 57 | 21 | 1.79 | (1.01, 3.16) |
5–10 years | 615 | 110 | 1.19 | (0.94, 1.49) | 153 | 4 | 0.49 | (0.16, 1.43) | 89 | 13 | 0.80 | (0.41, 1.54) | 53 | 8 | 0.62 | (0.27, 1.43) | 99 | 20 | 1.23 | (0.72, 2.11) |
>10 years | 820 | 173 | 1.36 | (1.12, 1.64) | 176 | 10 | 1.41 | (0.62, 3.18) | 111 | 12 | 0.53 | (0.28, 1.02) | 63 | 12 | 0.73 | (0.37, 1.47) | 120 | 20 | 0.75 | (0.44, 1.28) |
p-trend | <0.0001 | 0.90 | 0.06 | 0.18 | 0.98 | |||||||||||||||
p- heterogeneity | 0.71 | 0.01 | 0.58 | 0.31 | ||||||||||||||||
Hormone therapy use | ||||||||||||||||||||
Never | 7411 | 1085 | 1 | Reference | 1762 | 80 | 1 | Reference | 1010 | 183 | 1 | Reference | 573 | 113 | 1 | Reference | 991 | 196 | 1 | Reference |
Past | 4809 | 880 | 1.28 | (1.15, 1.43) | 1361 | 63 | 1.06 | (0.71, 1.59) | 688 | 132 | 1.09 | (0.82, 1.45) | 319 | 65 | 0.88 | (0.60, 1.30) | 575 | 126 | 1.04 | (0.79, 1.38) |
Estrogen current | 655 | 107 | 1.09 | (0.86, 1.37) | 162 | 5 | 0.77 | (0.27, 2.15) | 85 | 19 | 1.28 | (0.73, 2.26) | 51 | 12 | 1.12 | (0.54, 2.35) | 93 | 16 | 0.79 | (0.43, 1.46) |
Estrogen and progesterone current | 345 | 150 | 3.03 | (2.39, 3.83) | 89 | 3 | 0.80 | (0.21, 3.04) | 48 | 15 | 1.42 | (0.72, 2.78) | 32 | 6 | 0.88 | (0.33, 2.30) | 49 | 10 | 0.92 | (0.43, 1.98) |
p-trend | <0.0001 | 0.80 | 0.19 | 0.77 | 0.72 | |||||||||||||||
p-heterogeneity | 0.02 | 0.17 | 0.04 | 0.005 | ||||||||||||||||
Duration of hormone therapy (years) | ||||||||||||||||||||
Never used | 7411 | 1085 | 1 | Reference | 1762 | 80 | 1 | Reference | 1010 | 183 | 1 | Reference | 573 | 113 | 1 | Reference | 991 | 196 | 1 | Reference |
< =3 | 1625 | 246 | 1.10 | (0.93, 1.29) | 473 | 21 | 1.09 | (0.62, 1.91) | 237 | 43 | 1.01 | (0.67, 1.51) | 134 | 20 | 0.66 | (0.38, 1.16) | 234 | 41 | 0.77 | (0.52, 1.15) |
4–8 | 1130 | 197 | 1.19 | (0.99, 1.43) | 289 | 17 | 1.27 | (0.66, 2.45) | 155 | 31 | 1.14 | (0.71, 1.83) | 76 | 19 | 1.18 | (0.65, 2.13) | 119 | 25 | 0.99 | (0.59, 1.67) |
>8 | 1756 | 445 | 1.85 | (1.59, 2.15) | 485 | 23 | 1.01 | (0.56, 1.80) | 253 | 58 | 1.35 | (0.91, 2.02) | 108 | 23 | 0.93 | (0.52, 1.65) | 222 | 47 | 1.04 | (0.69, 1.56) |
p-trend | <0.0001 | 0.75 | 0.15 | 0.94 | 1.00 | |||||||||||||||
p-heterogeneity | 0.11 | 0.50 | 0.04 | 0.01 | ||||||||||||||||
Duration of estrogen and progesterone therapy (years) | ||||||||||||||||||||
Never | 7411 | 1085 | 1 | Reference | 1762 | 80 | 1 | Reference | 1010 | 183 | 1 | Reference | 573 | 113 | 1 | Reference | 991 | 196 | 1 | Reference |
< =5 | 1908 | 321 | 1.22 | (1.04, 1.42) | 545 | 25 | 1.08 | (0.62, 1.87) | 276 | 44 | 0.85 | (0.57, 1.27) | 153 | 30 | 0.92 | (0.56, 1.53) | 230 | 54 | 1.19 | (0.81, 1.74) |
>5 | 1796 | 454 | 1.82 | (1.57, 2.10) | 496 | 16 | 0.77 | (0.39, 1.50) | 256 | 64 | 1.41 | (0.95, 2.10) | 105 | 29 | 1.04 | (0.62, 1.74) | 211 | 52 | 1.34 | (0.89, 2.02) |
p-trend | <0.0001 | 0.65 | 0.30 | 0.98 | 0.13 | |||||||||||||||
p-heterogeneity | 0.002 | 0.33 | 0.18 | 0.02 |