Background
Methods
Study population and data collection
Assessment of biomarkers
Statistical analyses
Results
Characteristics of case participants and controls
Overall | By study | |||
---|---|---|---|---|
Women’s CARE | Women’s BCIS | Women’s LIFE | ||
Case participants |
N = 2658 |
N = 1197 |
N = 342 |
N = 1119 |
Mean age at diagnosis, years (SD, range) | 46.7 (8.1, 22-64) | 49.0 (8.6, 35-64) | 51.8 (7.3, 35-64) | 42.7 (5.4, 22-49) |
Race | ||||
White | 1960 (73.7%) | 678 (56.6%) | 287 (83.9%) | 995 (88.9%) |
African-American | 698 (26.3%) | 519 (43.4%) | 55 (16.1%) | 124 (11.1%) |
Subtype of breast cancer | ||||
Triple-negative | 554 (20.8%) | 335 (28.0%) | 21 (6.1%) | 198 (17.7%) |
Luminal A-like | 1517 (57.1%) | 645 (53.9%) | 233 (68.1%) | 639 (57.1%) |
Luminal B-like | 360 (13.5%) | 121 (10.1%) | 49 (14.3%) | 190 (17.0%) |
HER2-enriched | 227 (8.5%) | 96 (8.0%) | 39 (11.4%) | 92 (8.2%) |
Control participants |
N = 2448 |
N = 2011a
| ─ |
N = 437 |
Mean age at reference date, years (SD, range) | 47.8 (8.3, 24-64) | 48.9 (8.4, 35-64) | ─ | 42.6 (4.9, 24-49) |
Race | ||||
White | 1549 (63.3%) | 1147 (57.0%) | ─ | 402 (92.0%) |
African-American | 899 (36.7%) | 864 (43.0%) | ─ | 35 (8.0%) |
Mean age at menarche, years (SD) | 12.4 (1.6) | 12.4 (1.6) | ─ | 12.7 (1.5) |
Ever had a completed (>26-week) pregnancy | 1990 (81.3%) | 1677 (83.4%) | ─ | 313 (71.6%) |
Among parous women |
N = 1990 |
N = 1677 |
N = 313 | |
Mean number of completed pregnancies (SD) | 2.7 (1.5) | 2.8 (1.6) | ─ | 2.2 (1.1) |
Mean age at first completed pregnancy (SD) | 23.2 (5.7) | 22.5 (5.3) | ─ | 27.1 (6.2) |
Ever breastfed | 1242 (62.4%) | 967 (57.7%) | ─ | 275 (87.9%) |
Mean duration of breastfeeding among those who breastfed, months (SD) | 12.1 (15.0) | 10.9 (14.4) | ─ | 16.2 (16.5) |
Reproductive factors and risk of four ER/PR/HER2-defined subtypes
Controls | Triple-negative | Luminal A-like | Luminal B-like | HER2-enriched | |||||
---|---|---|---|---|---|---|---|---|---|
N
|
N
| OR (95% CI) |
N
| OR (95% CI) |
N
| OR (95% CI) |
N
| OR (95% CI) | |
All women | |||||||||
Age at menarche, years | |||||||||
≤ 12 | 1292 | 289 | 1.00 | 820 | 1.00 | 186 | 1.00 | 110 | 1.00 |
13 | 634 | 158 | 1.13 (0.90–1.41) | 419 | 0.98 (0.84–1.16) | 99 | 1.06 (0.81–1.40) | 66 | 1.22 (0.88–1.69) |
≥ 14 | 522 | 107 | 0.89 (0.69–1.14) | 278 | 0.77 (0.64–0.92) | 75 | 0.92 (0.68–1.24) | 51 | 1.07 (0.75–1.53) |
Trend P value |
0.55
|
0.009
|
0.70
|
0.56
| |||||
P value for homogeneity of trends |
0.19
| ||||||||
Number of completed pregnancies | |||||||||
Never pregnant | 250 | 68 | 1.00 | 224 | 1.00 | 56 | 1.00 | 31 | 1.00 |
Any completed pregnancies | 1990 | 431 | 0.91 (0.67–1.24) | 1104 | 0.79 (0.64–0.98) | 263 | 0.82 (0.58–1.15) | 176 | 0.78 (0.50–1.20) |
1 | 399 | 98 | 0.95 (0.66–1.36) | 277 | 0.92 (0.71–1.19) | 84 | 1.17 (0.79–1.74) | 50 | 1.02 (0.62–1.67) |
2 | 709 | 168 | 0.98 (0.70–1.37) | 438 | 0.81 (0.64–1.02) | 109 | 0.88 (0.61–1.29) | 59 | 0.69 (0.42–1.11) |
≥3 | 882 | 165 | 0.84 (0.60–1.19) | 389 | 0.64 (0.50–0.81) | 70 | 0.53 (0.35–0.80) | 67 | 0.65 (0.40–1.05) |
Trend P value |
0.26
|
<0.0001
|
<0.0001
|
0.02
| |||||
P value for homogeneity of trends |
0.09
| ||||||||
Only non-completed pregnancy | 208 | 55 | 0.91 (0.60–1.38) | 189 | 1.02 (0.76–1.35) | 41 | 0.88 (0.55–1.39) | 20 | 0.69 (0.38–1.26) |
Parous women onlya,b
| |||||||||
Age at first completed pregnancy, years | |||||||||
≤20 | 799 | 165 | 1.00 | 297 | 1.00 | 69 | 1.00 | 62 | 1.00 |
21–24 | 510 | 107 | 1.03 (0.78–1.38) | 274 | 1.22 (0.98–1.52) | 63 | 1.18 (0.80–1.73) | 43 | 1.05 (0.68–1.62) |
25–29 | 348 | 85 | 1.08 (0.77–1.52) | 275 | 1.64 (1.28–2.10) | 56 | 1.22 (0.78–1.89) | 33 | 1.10 (0.66–1.85) |
≥30 | 333 | 73 | 0.80 (0.54–1.20) | 256 | 1.17 (0.88–1.55) | 75 | 1.09 (0.68–1.74) | 38 | 0.96 (0.55–1.70) |
Trend P value |
0.50
|
0.05
|
0.57
|
0.95
| |||||
P value for homogeneity of trends |
0.24
| ||||||||
Duration of breastfeeding, months | |||||||||
Never | 748 | 166 | 1.00 | 370 | 1.00 | 81 | 1.00 | 60 | 1.00 |
Ever | 1242 | 264 | 0.80 (0.63–1.02) | 732 | 0.78 (0.65–0.94) | 182 | 0.89 (0.65–1.23) | 116 | 0.91 (0.63–1.32) |
< 6 | 541 | 134 | 0.96 (0.74–1.26) | 303 | 0.83 (0.68–1.02) | 82 | 0.99 (0.70–1.41) | 35 | 0.68 (0.43–1.07) |
6–11 | 263 | 40 | 0.55 (0.37–0.82) | 165 | 0.76 (0.59–0.99) | 35 | 0.70 (0.44–1.12) | 33 | 1.28 (0.78–2.09) |
≥ 12 | 438 | 90 | 0.69 (0.50–0.96) | 264 | 0.71 (0.56–0.90) | 65 | 0.85 (0.56–1.30) | 48 | 1.10 (0.69–1.75) |
Trend P value |
0.006
|
0.004
|
0.28
|
0.36
| |||||
P value for homogeneity of trends |
0.08
|
Reproductive factors and risk of TNBC and luminal A-like subtype by race
White women | African-American women | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Controls | Triple-negative | Luminal A-like | Controls | Triple-negative | Luminal A-like | |||||
N
|
N
| OR (95% CI) |
N
| OR (95% CI) |
N
|
N
| OR (95% CI) |
N
| OR (95% CI) | |
All women | ||||||||||
Age at menarche, years | ||||||||||
≤12 | 793 | 167 | 1.00 | 631 | 1.00 | 499 | 122 | 1.00 | 189 | 1.00 |
13 | 433 | 102 | 1.12 (0.84–1.48) | 327 | 0.90 (0.74–1.08) | 201 | 56 | 1.09 (0.75–1.58) | 92 | 1.18 (0.86–1.61) |
≥14 | 323 | 74 | 0.99 (0.72–1.36) | 220 | 0.78 (0.63–0.97) | 199 | 33 | 0.69 (0.44–1.06) | 58 | 0.75 (0.53–1.08) |
Trend P value |
0.89
|
0.02
|
0.16
|
0.26
| ||||||
P value for homogeneity of trends |
0.10
|
0.68
| ||||||||
Number of completed pregnancies | ||||||||||
Never pregnant | 199 | 56 | 1.00 | 200 | 1.00 | 51 | 12 | 1.00 | 24 | 1.00 |
Any completed pregnancies | 1213 | 246 | 0.87 (0.61–1.24) | 822 | 0.77 (0.61–0.97) | 777 | 185 | 1.18 (0.59–2.36) | 282 | 0.89 (0.51–1.54) |
1 | 240 | 58 | 0.91 (0.59–1.40) | 199 | 0.86 (0.65–1.16) | 159 | 40 | 1.14 (0.54–2.43) | 78 | 1.09 (0.60–1.97) |
2 | 468 | 112 | 0.99 (0.67–1.45) | 358 | 0.82 (0.63–1.06) | 241 | 56 | 1.12 (0.54–2.35) | 80 | 0.79 (0.44–1.42) |
≥3 | 505 | 76 | 0.69 (0.45–1.05) | 265 | 0.60 (0.45–0.79) | 377 | 89 | 1.24 (0.60–2.57) | 124 | 0.76 (0.43–1.36) |
Trend P value |
0.11
|
0.0005
|
0.62
|
0.13
| ||||||
P value for homogeneity of trends |
0.48
|
0.12
| ||||||||
Only non-completed pregnancy | 137 | 41 | 1.02(0.63–1.64) | 156 | 1.08 (0.78–1.49) | 71 | 14 | 0.86 (0.35–2.08) | 33 | 0.97 (0.49–1.90) |
Parous women onlya,b
| ||||||||||
Age at first completed pregnancy, years | ||||||||||
≤20 | 338 | 60 | 1.00 | 162 | 1.00 | 461 | 105 | 1.00 | 135 | 1.00 |
21–24 | 347 | 66 | 1.03 (0.68–1.56) | 199 | 1.09 (0.82–1.44) | 163 | 41 | 1.01 (0.65–1.58) | 75 | 1.40 (0.96–2.04) |
25–29 | 257 | 64 | 1.09 (0.69–1.70) | 227 | 1.55 (1.14–2.10) | 91 | 21 | 1.05 (0.59–1.89) | 48 | 1.75 (1.10–2.80) |
≥30 | 271 | 55 | 0.70 (0.42–1.17) | 232 | 1.13 (0.80–1.60) | 62 | 18 | 1.21 (0.61–2.41) | 24 | 0.95 (0.51–1.77) |
Trend P value |
0.21
|
0.10
|
0.62
|
0.24
| ||||||
P value for homogeneity of trends |
0.02
|
0.66
| ||||||||
Duration of breastfeeding, months | ||||||||||
Never | 368 | 66 | 1.00 | 228 | 1.00 | 380 | 100 | 1.00 | 142 | 1.00 |
Ever | 845 | 179 | 0.97 (0.68–1.38) | 592 | 0.81 (0.64–1.02) | 397 | 85 | 0.67 (0.47–0.96) | 140 | 0.78 (0.57–1.06) |
< 6 | 343 | 84 | 1.14 (0.78–1.68) | 230 | 0.85 (0.66–1.10) | 198 | 50 | 0.79 (0.52–1.19) | 73 | 0.82 (0.57–1.18) |
6–11 | 194 | 29 | 0.62 (0.37–1.05) | 134 | 0.75 (0.54–1.02) | 69 | 11 | 0.54 (0.26–1.09) | 31 | 1.06 (0.63–1.77) |
≥ 12 | 308 | 66 | 0.88 (0.56–1.39) | 228 | 0.77 (0.57–1.04) | 130 | 24 | 0.55 (0.32–0.94) | 36 | 0.57 (0.36–0.90) |
Trend P value |
0.27
|
0.07
|
0.01
|
0.04
| ||||||
P value for homogeneity of trends |
0.94
|
0.47
|
Reproductive factors and risk of TNBC and the luminal A-like subtype by age
Younger (20–44 years) | Oldera (45–64 years) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Controls | Triple-negative | Luminal A-like | Controls | Triple-negative | Luminal A-like | |||||
N
|
N
| OR (95% CI) |
N
| OR (95% CI) |
N
|
N
| OR (95% CI) |
N
| OR (95% CI) | |
All women | ||||||||||
Age at menarche, years | ||||||||||
≤12 | 491 | 139 | 1.00 | 299 | 1.00 | 801 | 150 | 1.00 | 521 | 1.00 |
13 | 252 | 94 | 1.35 (0.98–1.85) | 152 | 0.94 (0.72–1.22) | 382 | 64 | 0.90 (0.65–1.25) | 267 | 0.94 (0.77–1.16) |
≥14 | 227 | 58 | 0.86 (0.60–1.23) | 98 | 0.63 (0.47–0.85) | 295 | 49 | 0.85 (0.59–1.22) | 180 | 0.85 (0.67–1.08) |
Trend P value |
0.72
|
0.004
|
0.33
|
0.18
| ||||||
P-value for homogeneity of trends |
0.06
|
0.92
| ||||||||
Number of completed pregnancies | ||||||||||
Never pregnant | 115 | 47 | 1.00 | 91 | 1.00 | 135 | 21 | 1.00 | 133 | 1.00 |
Any completed pregnancies | 735 | 207 | 0.88 (0.58–1.32) | 368 | 0.75 (0.54–1.05) | 1255 | 224 | 1.06 (0.64–1.77) | 736 | 0.82 (0.62–1.09) |
1 | 193 | 48 | 0.75 (0.46–1.23) | 107 | 0.83 (0.56–1.23) | 206 | 50 | 1.30 (0.73–2.31) | 170 | 1.01 (0.72–1.42) |
2 | 289 | 83 | 0.94 (0.60–1.48) | 159 | 0.82 (0.57–1.19) | 420 | 85 | 1.15 (0.67–1.96) | 279 | 0.80 (0.59–1.09) |
≥ 3 | 253 | 76 | 0.98 (0.61–1.56) | 102 | 0.59 (0.40–0.88) | 629 | 89 | 0.85 (0.49–1.48) | 287 | 0.70 (0.51–0.96) |
Trend P value |
0.73
|
0.02
|
0.13
|
0.006
| ||||||
P value for homogeneity of trends |
0.03
|
0.83
| ||||||||
Only non-completed pregnancy | 120 | 37 | 0.91 (0.54–1.53) | 90 | 1.03 (0.68–1.57) | 88 | 18 | 1.08 (0.54–2.19) | 99 | 1.10 (0.74–1.65) |
Parous women onlyb,c
| ||||||||||
Age at first completed pregnancy, years | ||||||||||
≤ 20 | 235 | 71 | 1.00 | 85 | 1.00 | 564 | 94 | 1.00 | 212 | 1.00 |
21–24 | 142 | 43 | 1.02 (0.63–1.65) | 80 | 1.44 (0.95–2.17) | 368 | 64 | 1.05 (0.72–1.54) | 194 | 1.11 (0.85–1.44) |
25–29 | 168 | 50 | 0.94 (0.57–1.56) | 99 | 1.48 (0.97–2.27) | 180 | 35 | 1.20 (0.74–1.94) | 176 | 1.84 (1.34–2.51) |
≥30 | 190 | 42 | 0.62 (0.34–1.12) | 102 | 1.15 (0.71–1.86) | 143 | 31 | 1.08 (0.61–1.89) | 154 | 1.32 (0.91–1.90) |
Trend P value |
0.15
|
0.52
|
0.60
|
0.01
| ||||||
P value for homogeneity of trends |
0.07
|
0.27
| ||||||||
Duration of breastfeeding, months | ||||||||||
Never | 204 | 64 | 1.00 | 100 | 1.00 | 544 | 102 | 1.00 | 270 | 1.00 |
Ever | 531 | 142 | 0.75 (0.50–1.12) | 266 | 0.70 (0.50–0.99) | 711 | 122 | 0.85 (0.62–1.17) | 466 | 0.83 (0.67–1.03) |
< 6 | 209 | 69 | 0.93 (0.60–1.44) | 97 | 0.72 (0.49–1.05) | 332 | 65 | 0.97 (0.67–1.39) | 206 | 0.90 (0.70–1.16) |
6–11 | 126 | 22 | 0.49 (0.27–0.89) | 64 | 0.68 (0.44–1.07) | 137 | 18 | 0.62 (0.35–1.10) | 101 | 0.84 (0.60–1.17) |
≥ 12 | 196 | 51 | 0.60 (0.35–1.01) | 105 | 0.68 (0.44–1.05) | 242 | 39 | 0.79 (0.50–1.24) | 159 | 0.71 (0.53–0.96) |
Trend P value |
0.02
|
0.12
|
0.17
|
0.03
| ||||||
P value for homogeneity of trends |
0.32
|
0.93
|
Breastfeeding and risk of TNBC and luminal A-like breast cancer by race and age
White women | African-American women | |||||||||
---|---|---|---|---|---|---|---|---|---|---|
Controls | Triple-negative | Luminal A-like | Controls | Triple-negative | Luminal A-like | |||||
N
|
N
| OR (95% CI) |
N
| OR (95% CI) |
N
|
N
| OR (95% CI) |
N
| OR (95% CI) | |
Younger (20–44 years)a
| ||||||||||
Duration of breastfeeding, months | ||||||||||
Never | 85 | 27 | 1.00 | 57 | 1.00 | 119 | 37 | 1.00 | 43 | 1.00 |
Ever | 383 | 105 | 0.85 (0.49–1.49) | 218 | 0.71 (0.46–1.11) | 148 | 37 | 0.43 (0.22–0.83) | 48 | 0.58 (0.32–1.06) |
<6 | 136 | 43 | 0.94 (0.52–1.72) | 72 | 0.70 (0.43–1.14) | 73 | 26 | 0.67 (0.33–1.36) | 25 | 0.64 (0.32–1.26) |
≥6 | 247 | 62 | 0.76 (0.41–1.41) | 146 | 0.73 (0.45–1.18) | 75 | 11 | 0.18 (0.07–0.46) | 23 | 0.50 (0.24–1.06) |
Trend P value |
0.34
|
0.28
|
0.0004
|
0.07
| ||||||
P value for homogeneity of trends |
0.93
|
0.09
| ||||||||
Older (45–64 years)b
| ||||||||||
Duration of breastfeeding, months | ||||||||||
Never | 283 | 39 | 1.00 | 171 | 1.00 | 261 | 63 | 1.00 | 96 | 1.00 |
Ever | 462 | 74 | 1.06 (0.65–1.72) | 374 | 0.83 (0.63–1.10) | 249 | 48 | 0.74 (0.47–1.17) | 92 | 0.90 (0.62–1.30) |
< 6 | 207 | 41 | 1.30 (0.78–2.19) | 158 | 0.91 (0.67–1.25) | 125 | 24 | 0.69 (0.39–1.21) | 48 | 0.94 (0.60–1.46) |
≥ 6 | 255 | 33 | 0.75 (0.41–1.38) | 216 | 0.73 (0.53–1.02) | 124 | 24 | 0.81 (0.46–1.43) | 44 | 0.85 (0.54–1.35) |
Trend P value |
0.41
|
0.07
|
0.35
|
0.49
| ||||||
P value for homogeneity of trends |
0.85
|
0.72
|