Introduction
Methods
Navarre Breast Cancer Screening Program
Study cohort, baseline assessment, and follow-up
Statistical analysis
Results
Cause-specific hazards and hazard ratios from NBCSP cohort
Risk factor | No. of women | No. of woman-years | No. of invasive breast cancers | HR, NBCSP (95 % CI)a
| OR, Gail (95 % CI)b
|
---|---|---|---|---|---|
Age at menarche (years) | |||||
≥14 | 23,530 | 181,394 | 335 | 1.00 (reference) | 1.00 (reference) |
12–13 | 25,198 | 193,970 | 413 | 1.07 (0.97–1.19) | 1.10 (1.02–1.19) |
<12 | 5,921 | 45,436 | 87 | 1.15 (0.94–1.41) | 1.21 (1.03–1.41) |
Previous breast biopsy | |||||
Age <50 years | |||||
No | 12,289 | 29,166 | 42 | 1.00 (reference) | 1.00 (reference) |
Yes | 1,221 | 2,950 | 7 | 1.65 (0.74–3.67) | 1.89 (1.50–2.38)c
|
Age ≥50 years | |||||
No | 49,562 | 353,410 | 673 | 1.00 (reference) | 1.00 (reference) |
Yes | 4,966 | 35,274 | 113 | 1.67 (1.37–2.04) | 1.36 (1.19–1.56)c
|
No. of affected first-degree relatives | |||||
Age at first live birth <20 years | |||||
0 | 983 | 7,593 | 10 | 1.00 (reference) | 1.00 (reference) |
1 | 47 | 370 | 1 | 0.92 (0.45–1.87) | 2.61 (1.99–3.42) |
≥2 | 1 | 8 | 0 | 0.84 (0.20–3.51) | 6.80 (3.96–11.68) |
Age at first live birth 20–24 years | |||||
0 | 15,377 | 118,331 | 204 | 1.11 (1.01–1.23) | 1.24 (1.16–1.33) |
1 | 879 | 6,746 | 12 | 1.26 (0.81–1.95) | 2.68 (2.23–3.22) |
≥2 | 36 | 264 | 1 | 1.42 (0.62–3.28) | 5.78 (4.14–8.06) |
Age at first live birth 25–29 years or nulliparous | |||||
0 | 27,437 | 211,445 | 434 | 1.24 (1.01–1.52) | 1.55 (1.35–1.78) |
1 | 1,696 | 12,975 | 39 | 1.72 (1.28–2.32) | 2.76 (2.32–3.27) |
≥2 | 108 | 810 | 2 | 2.39 (1.48–3.88) | 4.91 (3.76–6.41) |
Age at first live birth ≥30 years | |||||
0 | 7,575 | 58,382 | 116 | 1.38 (1.02–1.88) | 1.93 (1.56–2.38) |
1 | 491 | 3,726 | 16 | 2.36 (1.51–3.67) | 2.83 (2.22–3.62) |
≥2 | 19 | 150 | 0 | 4.02 (1.82–8.88) | 4.17 (2.75–6.31) |
Age (years) | No. of woman-years | Invasive breast cancer | Death from other causes | ||||
---|---|---|---|---|---|---|---|
No. of cases | Baseline rate, NBCSP (95 % CI)a
| External baseline rate, Navarreb
| No. of deaths | Composite rate, NBCSP (95 % CI)c
| External composite rate, Navarred
| ||
45–49 | 32,116 | 49 | 111.3 (77.4–160.1) | 156.6 | 34 | 105.9 (75.6–148.2) | 115.2 |
50–54 | 96,663 | 185 | 138.9 (108.1–178.4) | 134.8 | 151 | 156.2 (133.2–183.2) | 166.6 |
55–59 | 100,953 | 202 | 144.0 (112.2–184.9) | 146.4 | 204 | 202.1 (176.2–231.8) | 239.7 |
60–64 | 86,085 | 193 | 160.4 (124.4–206.9) | 175.9 | 241 | 280.0 (246.8–317.6) | 327.8 |
65–69 | 77,621 | 166 | 152.8 (117.3–199.1) | 146.2 | 373 | 480.5 (434.2–531.9) | 619.5 |
70–74 | 27,362 | 40 | 104.3 (71.3–152.4) | 114.1 | 215 | 785.8 (687.4–898.1) | 1085.2 |
Calibration of prediction models
Stratum | Observed cases of invasive breast cancer | Navarre model | Original Gail modela
| Recalibrated Gail modela
| |||
---|---|---|---|---|---|---|---|
Expected cases of invasive breast cancerb
| Ratio of expected to observed cases (95 % CI)c
| Expected cases of invasive breast cancerb
| Ratio of expected to observed cases (95 % CI)c
| Expected cases of invasive breast cancerb
| Ratio of expected to observed cases (95 % CI)c
| ||
Age interval (years) | |||||||
45–49 | 49 | 48.87 | 1.00 (0.75–1.32) | 61.60 | 1.26 (0.95–1.66) | 50.81 | 1.04 (0.78–1.37) |
50–54 | 185 | 182.97 | 0.99 (0.86–1.14) | 208.61 | 1.13 (0.98–1.30) | 183.01 | 0.99 (0.86–1.14) |
55–59 | 202 | 198.90 | 0.98 (0.86–1.13) | 268.34 | 1.33 (1.16–1.52) | 201.40 | 1.00 (0.87–1.14) |
60–64 | 193 | 189.49 | 0.98 (0.85–1.13) | 281.55 | 1.46 (1.27–1.68) | 194.40 | 1.01 (0.87–1.16) |
65–69 | 166 | 161.72 | 0.97 (0.84–1.13) | 292.15 | 1.76 (1.51–2.05) | 167.14 | 1.01 (0.86–1.17) |
70–74 | 40 | 38.14 | 0.95 (0.70–1.30) | 103.24 | 2.58 (1.89–3.52) | 39.61 | 0.99 (0.73–1.35) |
Age at menarche (years) | |||||||
≥14 | 335 | 339.14 | 1.01 (0.91–1.13) | 508.56 | 1.52 (1.36–1.69) | 341.86 | 1.02 (0.92–1.14) |
12–13 | 413 | 385.28 | 0.93 (0.85–1.03) | 567.08 | 1.37 (1.25–1.51) | 395.11 | 0.96 (0.87–1.05) |
<12 | 87 | 95.68 | 1.10 (0.89–1.36) | 139.86 | 1.61 (1.30–1.98) | 99.41 | 1.14 (0.93–1.41) |
Previous breast biopsy | |||||||
Age <50 years | |||||||
No | 42 | 41.84 | 1.00 (0.74–1.35) | 51.60 | 1.23 (0.91–1.66) | 42.56 | 1.01 (0.75–1.37) |
Yes | 7 | 7.03 | 1.00 (0.48–2.11) | 10.00 | 1.43 (0.68–3.00) | 8.25 | 1.18 (0.56–2.47) |
Age ≥50 years | |||||||
No | 673 | 660.74 | 0.98 (0.91–1.06) | 1016.75 | 1.51 (1.40–1.63) | 691.11 | 1.03 (0.95–1.11) |
Yes | 113 | 110.48 | 0.98 (0.81–1.18) | 137.14 | 1.21 (1.01–1.46) | 94.45 | 0.84 (0.70–1.01) |
No. of affected first-degree relatives | |||||||
Age at first live birth <20 years | |||||||
0 | 10 | 11.85 | 1.18 (0.64–2.20) | 13.60 | 1.36 (0.73–2.53) | 9.60 | 0.96 (0.52–1.78) |
1 | 1 | 0.54 | 0.54 (0.10–21.35) | 1.72 | 1.72 (0.31–67.95) | 1.25 | 1.25 (0.22–49.28) |
≥2 | 0 | 0.01 | – | 0.12 | – | 0.06 | – |
Age at first live birth 20–24 years | |||||||
0 | 204 | 206.10 | 1.01 (0.88–1.16) | 259.50 | 1.27 (1.11–1.46) | 185.37 | 0.91 (0.79–1.04) |
1 | 12 | 13.47 | 1.12 (0.64–1.98) | 31.98 | 2.67 (1.51–4.69) | 22.84 | 1.90 (1.08–3.35) |
≥2 | 1 | 0.61 | 0.61 (0.11–23.98) | 2.60 | 2.60 (0.47–102.68) | 1.87 | 1.87 (0.34–73.89) |
Age at first live birth 25–29 years or nulliparous | |||||||
0 | 434 | 409.97 | 0.94 (0.86–1.04) | 600.26 | 1.38 (1.26–1.52) | 411.27 | 0.95 (0.86–1.04) |
1 | 39 | 35.33 | 0.91 (0.66–1.24) | 66.61 | 1.71 (1.25–2.34) | 45.08 | 1.16 (0.84–1.58) |
≥2 | 2 | 3.11 | 1.55 (0.43–12.83) | 7.50 | 3.75 (0.94–14.99) | 5.03 | 2.52 (0.63–10.06) |
Age at first live birth ≥30 years | |||||||
0 | 116 | 124.45 | 1.07 (0.89–1.29) | 210.19 | 1.81 (1.51–2.17) | 139.99 | 1.21 (1.01–1.45) |
1 | 16 | 13.77 | 0.86 (0.53–1.41) | 20.11 | 1.26 (0.77–2.05) | 13.23 | 0.83 (0.51–1.35) |
≥2 | 0 | 0.90 | – | 1.30 | – | 0.78 | – |
Overall | 835 | 820.10 | 0.98 (0.92–1.05) | 1215.49 | 1.46 (1.36–1.56) | 836.37 | 1.00 (0.94–1.07) |
Predicted 5-year risk (%) | No. of women | No. of woman-years | Observed cases of invasive breast cancer | Expected cases of invasive breast cancerb
| Ratio of expected to observed cases (95 % CI)c
|
---|---|---|---|---|---|
Navarre prediction model | |||||
0.40–0.81 | 10,930 | 84,233 | 154 | 129.95 | 0.84 (0.72–0.99) |
0.82–0.88 | 10,930 | 83,860 | 144 | 143.72 | 1.00 (0.85–1.18) |
0.89–0.95 | 10,929 | 84,274 | 155 | 154.16 | 0.99 (0.85–1.16) |
0.96–1.05 | 10,930 | 84,457 | 170 | 165.91 | 0.98 (0.84–1.13) |
1.06–5.59 | 10,930 | 83,976 | 212 | 226.36 | 1.07 (0.93–1.22) |
Original Gail prediction modela
| |||||
0.54–0.96 | 10,930 | 84,783 | 126 | 151.09 | 1.20 (1.01–1.43) |
0.97–1.18 | 10,931 | 84,260 | 156 | 190.94 | 1.22 (1.05–1.43) |
1.19–1.44 | 10,927 | 84,287 | 173 | 229.06 | 1.32 (1.14–1.54) |
1.45–1.74 | 10,931 | 84,041 | 175 | 273.13 | 1.56 (1.35–1.81) |
1.75–7.70 | 10,930 | 83,429 | 205 | 371.28 | 1.81 (1.58–2.08) |
Recalibrated Gail prediction modela
| |||||
0.39–0.77 | 10,930 | 84,296 | 138 | 120.15 | 0.87 (0.74–1.03) |
0.78–0.88 | 10,929 | 83,973 | 151 | 141.16 | 0.93 (0.80–1.10) |
0.89–0.98 | 10,930 | 84,138 | 158 | 157.62 | 1.00 (0.85–1.17) |
0.99–1.16 | 10,930 | 84,409 | 175 | 176.26 | 1.01 (0.87–1.17) |
1.17–4.96 | 10,930 | 83,984 | 213 | 241.18 | 1.13 (0.99–1.30) |
Discrimination of prediction models
Age (years) | No. of invasive breast cancers | No. of comparable pairsa
| Navarre prediction model | Gail prediction model | Discrimination difference (95 % CI)c
| ||
---|---|---|---|---|---|---|---|
No. of concordant pairsb
| Discrimination index (95 % CI)c
| No. of concordant pairsb
| Discrimination index (95 % CI)c
| ||||
45–49 | 49 | 44,932 | 25748.5 | 0.573 (0.497–0.649) | 25879.5 | 0.576 (0.501–0.651) | −0.003 (−0.015 to 0.009) |
50–54 | 185 | 378,725 | 206573.5 | 0.545 (0.502–0.589) | 209957.5 | 0.554 (0.512–0.597) | −0.009 (−0.031 to 0.013) |
55–59 | 202 | 447,830 | 240137.5 | 0.536 (0.492–0.580) | 243176.5 | 0.543 (0.499–0.587) | −0.007 (−0.029 to 0.016) |
60–64 | 193 | 368,818 | 199167.5 | 0.540 (0.496–0.584) | 195754.5 | 0.531 (0.488–0.574) | 0.009 (−0.001 to 0.019) |
65–69 | 166 | 271,740 | 145556.5 | 0.536 (0.490–0.581) | 145508.5 | 0.535 (0.490–0.581) | 0.000 (−0.011 to 0.011) |
70–74 | 40 | 31,467 | 19753.0 | 0.628 (0.531–0.725) | 19683.0 | 0.626 (0.534–0.717) | 0.002 (−0.038 to 0.042) |
Overall | 0.542 (0.521–0.564) | 0.544 (0.523–0.565) | −0.002 (−0.011 to 0.007) |