Introduction
Methods
Cohort
Ethics, consent and permissions
Study design
Assay methods
Statistical analysis
Results
Cohort
Analysis and presentation
Question | Group | No breast cancer | Breast cancer | OR (95 % CI) | Univariate summarya
| Age-adjusted summarya
|
---|---|---|---|---|---|---|
Age, yr | <52 | 10,601 (21 %) | 123 (18 %) | 0.85 (0.69–1.04) | 58 (52–64) | |
52–64 | 28,466 (57 %) | 387 (56 %) | 1.00 (reference) | 1.30 (1.14–1.48) | ||
>64 | 10,864 (22 %) | 187 (27 %) | 1.27 (1.06–1.51) | 15.9 (P < 0.001) | ||
Age at menarche, yr | <12 | 11,298 (23 %) | 168 (24 %) | 1.09 (0.89–1.31) | 13 (12–14) | |
12–13 | 20,817 (42 %) | 285 (41 %) | 1.00 (reference) | 0.99 (0.90–1.08) | 0.99 (0.90–1.08) | |
14+ | 16,685 (33 %) | 230 (33 %) | 1.01 (0.84–1.20) | 0.1 (P = 0.78) | 0.1 (P = 0.77) | |
Missing | 1131 (2 %) | 14 (2 %) | 0.90 (0.50–1.49) | |||
Parous | Yes | 43,578 (87 %) | 591 (85 %) | 1.00 (reference) | ||
No | 6166 (12 %) | 103 (15 %) | 1.23 (0.99–1.51) | 1.23 (0.99–1.51) | 1.28 (1.03–1.58) | |
Missing | 187 (0 %) | 3 (0 %) | 1.18 (0.29–3.12) | 3.6 (P = 0.059) | 5.0 (P = 0.026) | |
Age at birth of first child, yr | <21 | 11,134 (26 %) | 139 (24 %) | 0.91 (0.74–1.11) | 24 (20–27) | |
21–27 | 21,791 (50 %) | 300 (51 %) | 1.00 (reference) | 1.09 (0.98–1.22) | 1.13 (1.01–1.26) | |
>27 | 10,502 (24 %) | 150 (25 %) | 1.04 (0.85–1.26) | 2.4 (P = 0.12) | 4.4 (P = 0.037) | |
Missing | 151 (0 %) | 2 (0 %) | 0.96 (0.16–3.03) | |||
Age at menopause, yr | <46 | 16,201 (47 %) | 242 (47 %) | 0.73 (0.56–0.93) | 50 (45–51) | |
46–52 | 7933 (23 %) | 86 (17 %) | 1.00 (reference) | 1.30 (1.16–1.46) | 1.28 (1.14–1.44) | |
>52 | 4906 (14 %) | 90 (18 %) | 1.23 (0.96–1.56) | 21.4 (P < 0.001) | 18.4 (P < 0.001) | |
Missing | 5321 (15 %) | 95 (19 %) | 1.20 (0.94–1.51) | |||
BMI, kg/m2
| <25 | 17,538 (35 %) | 216 (31 %) | 1.00 (reference) | 26.5 (23.7–30.4) | |
25–30 | 16,633 (33 %) | 241 (35 %) | 1.18 (0.98–1.42) | 1.10 (1.01–1.21) | 1.11 (1.01–1.21) | |
30+ | 12,442 (25 %) | 192 (28 %) | 1.25 (1.03–1.52) | 4.6 (P = 0.033) | 4.8 (P = 0.028) | |
Missing | 3318 (7 %) | 48 (7 %) | 1.17 (0.85–1.59) | |||
BMI premenopause, kg/m2
| <25 | 1710 (38 %) | 18 (31 %) | 1.00 (reference) | 26.2 (23.3–30.1) | |
25–30 | 1394 (31 %) | 24 (41 %) | 1.64 (0.89–3.07) | 0.98 (0.71–1.33) | 0.98 (0.70–1.32) | |
30+ | 1087 (24 %) | 14 (24 %) | 1.22 (0.60–2.46) | 0.0 (P = 0.92) | 0.0 (P = 0.88) | |
Missing | 322 (7 %) | 3 (5 %) | 0.89 (0.21–2.63) | |||
BMI perimenopause, kg/m2
| <25 | 3176 (36 %) | 33 (34 %) | 1.00 (reference) | 26.4 (23.5–30.3) | |
25–30 | 2816 (32 %) | 33 (34 %) | 1.13 (0.69–1.84) | 1.00 (0.77–1.27) | 1.00 (0.77–1.27) | |
30+ | 2151 (25 %) | 25 (26 %) | 1.12 (0.66–1.88) | 0.0 (P = 0.99) | 0.0 (P = 0.99) | |
Missing | 601 (7 %) | 7 (7 %) | 1.12 (0.45–2.40) | |||
BMI postmenopause, kg/m2
| <25 | 11,918 (35 %) | 157 (31 %) | 1.00 (reference) | 26.5 (23.8–30.4) | |
25–30 | 11,767 (34 %) | 176 (34 %) | 1.14 (0.91–1.41) | 1.13 (1.02–1.25) | 1.14 (1.02–1.26) | |
30+ | 8603 (25 %) | 144 (28 %) | 1.27 (1.01–1.60) | 5.2 (P =0.023) | 5.5 (P = 0.019) | |
Missing | 2073 (6 %) | 36 (7 %) | 1.32 (0.90–1.88) | |||
First-degree relatives with breast cancer | 0 | 44,269 (89 %) | 595 (85 %) | 1.00 (reference) | ||
1 | 5257 (11 %) | 92 (13 %) | 1.30 (1.04–1.62) | 1.32 (1.09–1.58) | 1.30 (1.07–1.56) | |
2+ | 405 (1 %) | 10 (1 %) | 1.84 (0.91–3.27) | 7.8 (P =0.005) | 7.0 (P = 0.008) | |
Biopsies | No | 41,311 (83 %) | 530 (76 %) | 1.00 (reference) | ||
Yes | 7174 (14 %) | 136 (20 %) | 1.48 (1.22–1.78) | 1.48 (1.22–1.78) | 1.45 (1.19–1.75) | |
Missing | 14,46 (3 %) | 31 (4 %) | 1.67 (1.14–2.37) | 15.0 (P < 0.001) | 13.6 (P <0.001) | |
Current HRT by age group, yr, yes/no | <58, no | 23,758 (48 %) | 286 (41 %) | 1.00 (reference) | ||
<58, yes | 2529 (5 %) | 29 (4 %) | 0.95 (0.64–1.37) | 1.12 (0.82–1.49) | 1.43 (1.03–1.95) | |
58+, no | 22,328 (45 %) | 354 (51 %) | 1.32 (1.13–1.54) | 0.5 (P = 0.47) | 4.7 (P = 0.031) | |
58+, yes | 1316 (3 %) | 28 (4 %) | 1.77 (1.17–2.57) |
No cancer, median (IQR) | Cancer, median (IQR) | IQR-ORa (95 % CI) | IQR-ORb (95 % CI) | LRa-χ2
| LRb-Δχ2
| AUCa (95 % CI) | AUCb (95 % CI) | |
---|---|---|---|---|---|---|---|---|
Primary: invasive + DCIS | ||||||||
Number of women | 49,931 | 697 | ||||||
Gail | 3.50 % (2.90–4.40 %) | 3.70 % (3.10–4.60 %) | 1.22 (1.12–1.33) | 1.21 (1.10–1.31) | 19.7 | 0.55 (0.52–0.57) | ||
Density residual | −0.06 (−0.73–0.63) | 0.24 (−0.40–0.91) | 1.48 (1.34–1.63) | 1.47 (1.33–1.62) | 61.4 | 58.6 | 0.59 (0.57–0.61) | 0.59 (0.57–0.61) |
Tyrer-Cuzick | 2.66 % (2.12–3.47 %) | 2.94 % (2.28–3.97 %) | 1.36 (1.25–1.48) | 1.34 (1.23–1.45) | 49.2 | 0.57 (0.55–0.59) | ||
Density residual | −0.06 (−0.73–0.63) | 0.24 (−0.40–0.91) | 1.48 (1.34–1.63) | 1.45 (1.32–1.60) | 61.4 | 54.8 | 0.59 (0.57–0.61) | 0.61 (0.59–0.63) |
Secondary: invasive | ||||||||
Number of women | 50,061 | 567 | ||||||
Gail | 3.50 % (2.90–4.40 %) | 3.70 % (3.00–4.55 %) | 1.19 (1.07–1.31) | 1.17 (1.06–1.29) | 11.3 | 0.54 (0.52–0.56) | ||
Density residual | −0.06 (−0.73–0.63) | 0.24 (−0.40–0.85) | 1.47 (1.32–1.64) | 1.46 (1.31–1.63) | 48.5 | 46.6 | 0.59 (0.56–0.61) | 0.59 (0.57–0.61) |
Tyrer-Cuzick | 2.66 % (2.12–3.47 %) | 2.93 % (2.29–3.88 %) | 1.33 (1.21–1.46) | 1.30 (1.18–1.43) | 33.6 | 33.6 | 0.57 (0.55–0.59) | |
Density residual | −0.06 (−0.73–0.63) | 0.24 (−0.40–0.85) | 1.47 (1.32–1.64) | 1.46 (1.31–1.63) | 48.5 | 43.7 | 0.59 (0.56–0.61) | 0.61 (0.58–0.63) |
Calibration: O/E (95 % CI) | Discrimination: AUC (95 % CI) | ||||
---|---|---|---|---|---|
Age group, yr | Cases/total (%) | Tyrer-Cuzick | Gail | Tyrer-Cuzick | Gail |
47–49 | 170/13,662 (1.2 %) | 51 % (16–85 %) | 43 % (−4–88 %) | 0.57 (0.52–0.61) | 0.54 (0.50–0.59) |
50–54 | 125/10,677 (1.2 %) | 52 % (14–89 %) | 44 % (−8–93 %) | 0.55 (0.49–0.60) | 0.54 (0.49–0.59) |
55–59 | 42/4312 (1.0 %) | 70 % (−2–138 %) | 33 % (−75–135 %) | 0.58 (0.49–0.67) | 0.53 (0.45–0.62) |
60–64 | 147/8244 (1.8 %) | 79 % (42–114 %) | 17 % (−33–64 %) | 0.62 (0.58–0.66) | 0.52 (0.48–0.57) |
65–69 | 173/10,926 (1.6 %) | 44 % (10–76 %) | 17 % (−29–60 %) | 0.54 (0.50–0.59) | 0.51 (0.46–0.55) |
70–73 | 40/2807 (1.4 %) | 122 % (54–188 %) | 99 % (19–172 %) | 0.64 (0.55–0.73) | 0.58 (0.48–0.68) |
Risk model combined with density (10-year risk) | |||||||
---|---|---|---|---|---|---|---|
Risk model | <1 % | 1–2 % | 2–3.5 % | 3.5–5 % | 5–8 % | >8 % | Total |
Tyrer-Cuzick | |||||||
<1 % | 0/60 (0.0 %) |
0/18 (0.0 %)
| 0/78 (0.0 %) | ||||
1–2 % | 4/700 (0.6 %) | 60/6910 (0.9 %) |
18/1976 (0.9 %)
|
2/85 (2.4 %)
|
0/8 (0.0 %)
| 84/9679 (0.9 %) | |
2–3.5 % | 0/6 (0.0 %) | 69/7425 (0.9 %) | 221/16,515 (1.3 %) |
75/3807 (2.0 %)
|
16/652 (2.5 %)
|
1/24 (4.2 %)
| 382/28,429 (1.3 %) |
3.5–5 % | 0/29 (0.0 %) | 21/2689 (0.8 %) | 66/3139 (2.1 %) |
35/1508 (2.3 %)
|
2/139 (1.4 %)
| 124/7504 (1.7 %) | |
5–8 % | 3/144 (2.1 %) | 20/1181 (1.7 %) | 48/2257 (2.1 %) |
16/758 (2.1 %)
| 87/4340 (2.0 %) | ||
>8 % | 0/2 (0.0 %) | 5/172 (2.9 %) | 15/424 (3.5 %) | 20/598 (3.3 %) | |||
Total | 4/766 (0.5 %) | 129/14,382 (0.9 %) | 263/21324 (1.2 %) | 163/8214 (2.0 %) | 104/4597 (2.3 %) | 34/1345 (2.5 %) | 697/50,628 (1.4 %) |
Gail | |||||||
<1 % | |||||||
1–2 % | 0/17 (0.0 %) | 5/601 (0.8 %) |
5/257 (1.9 %)
|
0/14 (0.0 %)
| 10/889 (1.1 %) | ||
2–3.5 % | 0/1 (0.0 %) | 33/4286 (0.8 %) | 170/14,115 (1.2 %) |
62/3894 (1.6 %)
|
15/756 (2.0 %)
|
0/42 (0.0 %)
| 280/23,094 (1.2 %) |
3.5–5 % | 1/90 (1.1 %) | 68/7048 (1.0 %) | 118/7751 (1.5 %) |
75/3533 (2.1 %)
|
11/315 (3.5 %)
| 273/18,737 (1.5 %) | |
5–8 % | 3/277 (1.1 %) | 21/1851 (1.1 %) | 63/3610 (1.7 %) |
20/1105 (1.8 %)
| 107/6843 (1.6 %) | ||
>8 % | 0/15 (0.0 %) | 8/316 (2.5 %) | 19/734 (2.6 %) | 27/1065 (2.5 %) | |||
Total | 0/18 (0.0 %) | 39/4977 (0.8 %) | 246/21,697 (1.1 %) | 201/13,525 (1.5 %) | 161/8215 (2.0 %) | 50/2196 (2.3 %) | 697/50,628 (1.4 %) |