Introduction
Methods
Study population
Tumor characteristics
Risk factor information
Multiple imputation
Statistical analysis
Results
Tumor characteristics by patient characteristics, age at breast cancer diagnosis, and BBD calendar year at diagnosis
Age at breast cancer diagnosis | ER status | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
Cases | ≤ 50 years (N = 69) | > 50 years (N = 445) | Pa | ER+ (N = 391) | ER− (N = 64) | Pa | ||||||
N | % | N | % | N | % | N | % | N | % | |||
Age at BBD, years | ||||||||||||
< 40 | 90 | 17.5 | 41 | 59.4 | 49 | 11.0 | < 0.0001 | 61 | 15.6 | 13 | 20.3 | 0.83 |
40–49 | 141 | 27.4 | 28 | 40.6 | 113 | 25.4 | 113 | 28.9 | 17 | 26.6 | ||
50–59 | 145 | 28.2 | 0 | 0 | 145 | 32.6 | 111 | 28.4 | 19 | 29.7 | ||
60–69 | 86 | 16.7 | 0 | 0 | 86 | 9.3 | 65 | 16.6 | 8 | 12.5 | ||
≥ 70 | 52 | 10.1 | 0 | 0 | 52 | 11.7 | 41 | 10.5 | 7 | 10.9 | ||
Mean (SD) | 52.2 (12.5) | 37.5 (6.9) | 54.4 (11.6) | 52.4 (12.5) | 51.7 (12.9) | |||||||
Median (IQR) | 51.5 (42.6, 60.8) | 39.0 (34.9, 42.9) | 53.6 (46.1, 62.1) | 51.7 (42.8, 61.0) | 50.6 (42.8, 59.8) | |||||||
Year of BBD diagnosis | 0.062 | 0.92 | ||||||||||
1971–1979 | 95 | 18.5 | 19 | 27.5 | 76 | 17.1 | 50 | 12.8 | 10 | 15.6 | ||
1980–1989 | 173 | 33.7 | 16 | 23.2 | 157 | 35.3 | 134 | 34.3 | 20 | 31.3 | ||
1990–1999 | 161 | 31.3 | 25 | 36.2 | 136 | 30.6 | 134 | 34.3 | 22 | 34.4 | ||
2000–2006# | 85 | 16.5 | 9 | 13.0 | 76 | 17.1 | 73 | 18.7 | 12 | 18.8 | ||
BBD histology | 0.22 | 0.39 | ||||||||||
Normal/non-proliferative | 324 | 63.0 | 50 | 72.5 | 274 | 61.6 | 243 | 62.2 | 43 | 67.2 | ||
Proliferative without atypia | 163 | 31.7 | 16 | 23.2 | 147 | 33.3 | 127 | 32.5 | 20 | 31.3 | ||
Proliferative with atypia | 27 | 5.3 | 3 | 4.4 | 24 | 5.4 | 21 | 5.4 | 1 | 1.6 | ||
Year of breast cancer diagnosis | < 0.0001 | 0.53 | ||||||||||
1973–1990 | 72 | 14.1 | 22 | 31.9 | 51 | 11.4 | 21 | 5.4 | 3 | 4.7 | ||
1991–1995 | 68 | 13.2 | 10 | 14.5 | 58 | 13.0 | 49 | 12.5 | 12 | 18.8 | ||
1996–2000 | 101 | 19.7 | 17 | 24.6 | 84 | 18.8 | 81 | 20.7 | 17 | 26.6 | ||
2001–2005 | 116 | 22.6 | 11 | 15.9 | 106 | 23.7 | 104 | 26.6 | 12 | 18.8 | ||
2006–2010 | 106 | 20.6 | 5 | 7.3 | 101 | 22.6 | 91 | 23.3 | 14 | 21.9 | ||
2011–2013 | 51 | 9.9 | 4 | 5.8 | 47 | 10.6 | 45 | 11.5 | 6 | 9.4 | ||
Years from BBD to breast cancer diagnosis | < 0.0001 | 0.55 | ||||||||||
≤ 10 | 284 | 55.3 | 54 | 78.3 | 230 | 51.7 | 198 | 50.6 | 35 | 54.7 | ||
> 10 | 230 | 44.8 | 15 | 21.7 | 215 | 48.3 | 193 | 49.4 | 29 | 45.3 | ||
Mean (SD) | 10.8 (7.9) | 7.3 (6) | 11.4 (8) | 11.6 (8) | 10.5 (8.3) | |||||||
Median (IQR) | 9.0 (4.4, 15.8) | 5.6 (2.9, 9.4) | 9.8 (4.7, 16.3) | 10.0 (5.3, 16.4) | 8.7 (3.3, 15.7) | |||||||
Tumor size/mm | 0.13 | 0.63 | ||||||||||
< 10 | 143 | 28.9 | 26 | 37.7 | 117 | 27.5 | 90 | 23.9 | 16 | 26.2 | ||
10–20 | 211 | 42.6 | 29 | 42.0 | 182 | 42.7 | 173 | 45.9 | 24 | 39.3 | ||
> 20 | 141 | 28.5 | 14 | 20.3 | 127 | 29.8 | 114 | 30.2 | 21 | 34.4 | ||
Missing | 19 | 0 | 19 | 14 | 3 | |||||||
Tumor gradec | 0.14 | < 0.0001 | ||||||||||
Well differentiated | 141 | 34.7 | 14 | 31.8 | 127 | 34.9 | 134 | 39.3 | 5 | 8.6 | ||
Moderately differentiated | 159 | 38.9 | 13 | 29.6 | 146 | 40.1 | 149 | 43.7 | 6 | 10.3 | ||
Poorly differentiated | 108 | 26.4 | 17 | 38.6 | 91 | 25.0 | 58 | 17.0 | 47 | 81.0 | ||
Not determined | 106 | 25 | 81 | 50 | 6 | |||||||
ER | 0.026 | – | ||||||||||
Negative | 64 | 14.1 | 12 | 24.5 | 52 | 12.8 | – | – | – | – | ||
Positive | 391 | 85.9 | 37 | 75.5 | 354 | 87.2 | – | – | – | – | ||
Missing/unknown | 59 | 20 | 39 | – | – | – | – | |||||
PR | 0.53 | < 0.0001 | ||||||||||
Negative | 131 | 28.9 | 16 | 32.7 | 115 | 28.4 | 73 | 18.7 | 58 | 90.6 | ||
Positive | 323 | 71.2 | 33 | 67.4 | 290 | 71.6 | 317 | 81.3 | 6 | 9.4 | ||
Missing/unknown | 60 | 20 | 40 | 1 | 0 | |||||||
HER2d | 0.99b | 0.0028 | ||||||||||
Negative | 224 | 79.4 | 17 | 73.9 | 207 | 79.9 | 203 | 81.5 | 20 | 62.5 | ||
Positive | 50 | 17.7 | 4 | 17.4 | 46 | 17.8 | 38 | 15.3 | 12 | 37.5 | ||
Equivocal | 8 | 2.8 | 2 | 8.7 | 6 | 2.3 | 8 | 3.2 | 0 | 0.0 | ||
Missing/unknown | 232 | 46 | 186 | 142 | 32 | |||||||
Regional lymph nodes | 0.98 | 0.11 | ||||||||||
Negative | 337 | 73.6 | 47 | 73.4 | 230 | 73.6 | 264 | 74.6 | 36 | 64.3 | ||
Positive | 121 | 26.4 | 17 | 26.6 | 104 | 26.4 | 90 | 25.4 | 20 | 35.7 | ||
Missing | 56 | 5 | 51 | 37 | 8 | |||||||
Tumor histology | 0.54b | 0.14b | ||||||||||
Ductal | 439 | 83.5 | 59 | 85.5 | 370 | 83.2 | 322 | 82.4 | 54 | 84.4 | ||
Lobular | 48 | 9.3 | 8 | 11.6 | 40 | 9.0 | 39 | 10.0 | 4 | 6.3 | ||
Mixed ductal/lobular | 26 | 5.1 | 2 | 2.9 | 24 | 5.4 | 23 | 5.9 | 2 | 3.1 | ||
Others | 11 | 2.1 | 0 | 0.0 | 11 | 2.5 | 7 | 1.8 | 4 | 6.3 | ||
Tumor stage | 0.46b | 0.30b | ||||||||||
I | 262 | 58.0 | 32 | 62.8 | 230 | 57.4 | 223 | 59.3 | 29 | 47.5 | ||
II | 150 | 33.2 | 13 | 25.5 | 137 | 34.2 | 120 | 31.9 | 25 | 41.0 | ||
III | 29 | 6.4 | 4 | 7.8 | 25 | 6.2 | 24 | 6.4 | 5 | 8.2 | ||
IV | 11 | 2.4 | 2 | 3.9 | 9 | 2.2 | 9 | 2.4 | 2 | 3.3 | ||
Missing | 62 | 18 | 44 | 15 | 3 |
Breast cancer risk factors among women with BBD
Breast cancer risk by ER status among women with BBD
Variable | Controls (N = 514) | Cases, ER+ (N = 391) | ER+ vs. controls | Cases, ER− (N = 64) | ER− vs. controls | P-het† | |||
---|---|---|---|---|---|---|---|---|---|
Na | %a | Na | %a | OR (95% CI)* | Na | %a | OR (95% CI)* | ||
Age at first full-term birth/years | |||||||||
Nulliparous/≥ 30 | 108 | 20.9 | 88 | 27.6 | 1.00 (ref) | 13 | 20.3 | 1.00 (ref) | 0.24 |
< 30 | 406 | 79.1 | 231 | 72.4 | 0.69 (0.49, 0.98) | 51 | 79.7 | 1.08 (0.51, 2.30) | |
P-value | 0.038 | 0.84 | |||||||
Family history of breast cancer | |||||||||
No | 434 | 84.4 | 257 | 80.7 | 1.00 (ref) | 50 | 77.5 | 1.00 (ref) | 0.56 |
Yes | 80 | 15.6 | 62 | 19.3 | 1.30 (0.89, 1.88) | 14 | 22.5 | 1.60 (0.77, 3.33) | |
P-value | 0.17 | 0.20 | |||||||
History of bilateral oophorectomy | |||||||||
No | 429 | 83.4 | 346 | 88.6 | 1.00 (ref) | 55 | 85.9 | 1.00 (ref) | 0.42 |
Yes | 85 | 16.6 | 45 | 11.4 | 0.59 (0.38, 0.90) | 9 | 14.1 | 0.82 (0.37, 1.80) | |
P-value | 0.015 | 0.62 | |||||||
BBD histology | |||||||||
Normal/non-proliferative | 384 | 74.7 | 243 | 62.2 | 1.00 (ref) | 43 | 67.2 | 1.00 (ref) | 0.45 |
Proliferative without atypia | 124 | 24.1 | 127 | 32.5 | 1.70 (1.25, 2.30) | 20 | 31.3 | 1.49 (0.84, 2.67) | |
Proliferative with atypia | 6 | 1.2 | 21 | 5.4 | 5.48 (2.14, 14.01) | 1 | 1.6 | – | |
P-trend | < 0.0001 | – | |||||||
Subjective impression of involution | |||||||||
None/mildly involuted (0–24%) | 235 | 45.7 | 187 | 47.8 | 1.00 (ref) | 27 | 42.2 | 1.00 (ref) | 0.85 |
Partially involuted (25–74%) | 75 | 14.6 | 78 | 20.0 | 1.38 (0.93, 2.04) | 12 | 18.8 | 1.48 (0.70, 3.13) | |
Completely involuted (≥ 75%) | 135 | 26.3 | 84 | 21.5 | 0.87 (0.61, 1.24) | 15 | 23.4 | 1.07 (0.53, 2.13) | |
No TDLU observed | 69 | 13.4 | 42 | 10.7 | 0.69 (0.43, 1.10) | 10 | 15.6 | 1.28 (0.57, 2.91) | |
P-trendb | 0.68 | 0.90 | |||||||
Columnar cell lesionsc | |||||||||
None | 450 | 87.9 | 328 | 84.1 | 1.00 (ref) | 53 | 82.8 | 1.00 (ref) | 0.94 |
Present with/without atypia | 62 | 12.1 | 62 | 15.9 | 1.54 (1.03, 2.29) | 11 | 17.2 | 1.50 (0.73, 3.07) | |
P-value | 0.034 | 0.27 |
Breast cancer risk by grade and tumor size among women with BBD
Breast cancer risk by menopausal status at BBD diagnosis and before and after 1993
Variable | Premenopausal women, N = 449a | Postmenopausal women, N = 579a | P-het† | ||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Control N = 217 | Case N = 233 | Multivariable model* | Control N = 297 | Case N = 282 | Multivariable model* | ||||||
Na | %a | Na | %a | OR (95% CI)* | Na | %a | Na | %a | OR (95% CI)* | ||
Age at first full-term birth/years | |||||||||||
Nulliparous/≥ 30 | 57 | 26.3 | 83 | 35.7 | 1.00 (ref) | 50 | 17.0 | 56 | 20.0 | 1.00 (ref) | 0.35 |
< 30 | 160 | 73.7 | 150 | 64.3 | 0.59 (0.38, 0.90) | 247 | 83.0 | 226 | 80.0 | 0.81 (0.47, 1.38) | |
P-value | 0.015 | 0.43 | |||||||||
Family history of breast cancer | |||||||||||
No | 190 | 87.5 | 186 | 80.0 | 1.00 (ref) | 244 | 82.2 | 225 | 79.9 | 1.00 (ref) | 0.28 |
Yes | 27 | 12.5 | 47 | 20.0 | 1.75 (1.00, 3.07) | 53 | 17.8 | 57 | 20.1 | 1.18 (0.76, 1.83) | |
P-value | 0.052 | 0.46 | |||||||||
History of bilateral oophorectomy | |||||||||||
No | – | – | – | – | – | 212 | 71.3 | 221 | 78.3 | 1.00 (ref) | – |
Yes | – | – | – | – | – | 85 | 28.7 | 61 | 21.7 | 0.66 (0.44, 0.99) | |
P-value | – | 0.044 | |||||||||
BBD histology | |||||||||||
Normal/non-proliferative | 178 | 81.9 | 157 | 67.5 | 1.00 (ref) | 206 | 69.5 | 167 | 59.4 | 1.00 (ref) | 0.47 |
Proliferative without atypia | 37 | 17.2 | 67 | 28.7 | 2.06 (1.27, 3.33) | 87 | 29.2 | 97 | 34.2 | 1.41 (0.97, 2.03) | |
Proliferative with atypia | 2 | 0.9 | 9 | 3.9 | 5.45 (1.14, 26.15) | 4 | 1.4 | 18 | 6.4 | 5.65 (1.86, 17.14) | |
P-trend | 0.015 | 0.41 | |||||||||
Columnar cell lesionsb | |||||||||||
None | 179 | 83.2 | 188 | 81.1 | 1.00 (ref) | 271 | 91.3 | 238 | 84.6 | 1.00 (ref) | 0.09 |
Present with/without atypia | 36 | 16.9 | 44 | 18.9 | 1.09 (0.65, 1.82) | 26 | 8.7 | 43 | 15.4 | 2.08 (1.21, 3.58) | |
P-value | 0.73 | 0.008 |