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Table 5 Adjusted odds ratios (OR) and 95% confidence intervals (CI) for association between breast cancer subtypes and reproductive and hormonal factors with grade included in the luminal-like subtypes

From: Parity, hormones and breast cancer subtypes - results from a large nested case-control study in a national screening program

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  
  1. *p for trend and OR mutually adjusted for age (50–54, 55–59, 60–64, 65–70 years at screening), body mass index (BMI) (≤22, 23–25, 26–28, >28 at screening), education (no education/primary school, high school, bachelor’s or master’s degree), age at menarche (9–12, 13, 14, 15–18 years), number of pregnancies (0, 1, 2, 3, ≥4), menopausal status (premenopausal, perimenopausal, postmenopausal). # p for heterogeneity across subtypes was determined in a case–case model (see “Methods”)