Background
Methods
Study design and population
Data collection
Drug use assessment
Statistical methods
Results
Variable | Category | Cases | Controls | p |
---|---|---|---|---|
Age, mean ± sd | 56.4 ± 12.6 | 59.0 ± 13.2 | <0.001 | |
Geographical area, n (%) | Asturias | 70 (4.0) | 121 (6.4) | |
Barcelona | 292 (16.8) | 380 (20.1) | ||
Cantabria | 141 (8.1) | 188 (9.9) | ||
Gerona | 47 (2.7) | 57 (3.0) | ||
Guipuzcoa | 226 (13.0) | 255 (13.5) | ||
Huelva | 105 (6.1) | 79 (4.2) | ||
Leon | 227 (13.1) | 202 (10.7) | ||
Madrid | 341 (19.6) | 365 (19.3) | ||
Navarra | 226 (13.0) | 181 (9.6) | ||
Valencia | 61 (3.5) | 67 (3.5) | <0.001 | |
Family history of breast cancer, n (%) | No | 1288 (75.0) | 1628 (85.7) | |
First-degree relative | 256 (14.9) | 166 (8.7) | ||
Second-degree relative | 174 (10.1) | 106 (5.8) | <0.001 | |
Educational level, n (%) | Less than primary school | 268 (15.4) | 327 (17.3) | |
Primary school | 565 (32.6) | 581 (30.7) | ||
Secondary school | 573 (33.0) | 585 (30.9) | ||
University | 330 (19.0) | 402 (21.2) | 0.10 | |
Tobacco smoking, n (%) | Never smoker | 972 (56.0) | 1141 (60.2) | |
Former smoker | 450 (25.9) | 397 (21.0) | ||
Current smoker | 314 (18.1) | 357 (18.8) | 0.002 | |
Body Mass Index (kg/m2), n (%) | <18.5 | 30 (1.7) | 43 (2.3) | |
18.5–24.9 | 789 (45.5) | 899 (47.4) | ||
25.0–29.9 | 590 (34.0) | 601 (31.7) | ||
≥30 | 327 (18.8) | 352 (18.6) | 0.31 | |
Energy intake (kcal/day), mean ± sd | 1861 ± 644 | 1754 ± 566 | <0.001 | |
Ethanol intake (g/day), mean ± sd | 6.2 ± 11.5 | 5.3 ± 9.5 | 0.01 | |
Red meat intake (g/day), mean ± sd | 26.9 ± 20.2 | 25.2 ± 19.9 | 0.01 | |
Fruit intake (g/day), mean ± sd | 363 ± 239 | 365 ± 222 | 0.87 | |
Vegetable intake (g/day), mean ± sd | 196 ± 133 | 198 ± 119 | 0.60 | |
Dairy intake (g/day), mean ± sd | 321.1 ± 177.1 | 328.7 ± 176.7 | 0.24 | |
Number of deliveries, mean ± sd | 1.9 ± 1.5 | 2.0 ± 1.6 | 0.03 | |
Menopausal status, n (%) | Premenopausal | 702 (40.4) | 628 (33.1) | |
Postmenopausal | 1034 (59.6) | 1267 (66.9) | <0.001 | |
Age at first delivery, mean ± sd | 26.5 ± 5.0 | 26.5 ± 4.7 | 0.82 | |
Age at menarche, mean ± sd | 12.8 ± 1.5 | 12.9 ± 1.5 | 0.02 | |
Age at menopause, mean ± sd | 48.8 ± 5.4 | 48.5 ± 5.3 | 0.18 | |
Previous use of hormonal contraceptives, n (%) | 789 (45.5) | 868 (45.8) | 0.83 |
Classification | N (%) |
---|---|
Pathology | |
Ductal | 1289 (74.3) |
Lobular | 112 (6.5) |
Papilar | 22 (1.3) |
Coloid | 20 (1.2) |
Tubular | 12 (0.7) |
Mixed | 27 (1.6) |
Other | 35 (2.0) |
Not Available | 213 (12.3) |
Clinical stage | |
0 | 115 (6.6) |
I | 604 (34.8) |
II | 495 (28.5) |
III | 182 (10.5) |
IV | 22 (1.3) |
Not Available | 196 (11.3) |
Inmunohistochemistry | |
Progesterone | 992 (62.5) |
Estrogens | 1147 (72.2) |
HER2 | 227 (14.3) |
Triple negative | 92 (5.8) |
NSAID consumption and breast cancer according to women’s characteristics
Population | NSAID | Unexposed controls/cases (n) | Exposed controls/Cases (n) | OR (95 % CI) | p |
---|---|---|---|---|---|
All women | NSAID (all) | 1170/1111 | 739/625 | 0.76 (0.64–0.89) | 0.001 |
Aspirin | 1807/1653 | 102/83 | 0.91 (0.64–1.29) | 0.60 | |
Acetic acid derivatives | 1753/1620 | 156/116 | 0.75 (0.55–1.01) | 0.06 | |
Propionic acid derivatives | 1350/1232 | 559/504 | 0.82 (0.69–0.98) | 0.03 | |
cox2 inhibitors | 1891/1731 | 18/5 | 0.28 (0.09–0.88) | 0.03 | |
NSAID others | 1861/1697 | 48/39 | 1.13 (0.67–1.89) | 0.65 | |
Premenopausal | NSAID (all) | 361/415 | 267/287 | 0.80 (0.60–1.07) | 0.14 |
Aspirin | 613/689 | 15/13 | 0.60 (0.25–1.47) | 0.27 | |
Acetic acid derivatives | 600/664 | 28/38 | 0.75 (0.42–1.36) | 0.35 | |
Propionic acid derivatives | 392/451 | 236/251 | 0.84 (0.62–1.13) | 0.24 | |
cox2 inhibitors | 626/701 | 2/1 | - | - | |
NSAID others | 618/693 | 10/9 | 1.26 (0.41–3.9) | 0.69 | |
Postmenopausal | NSAID (all) | 804/696 | 462/338 | 0.69 (0.56–0.86) | <0.001 |
Aspirin | 1180/964 | 86/70 | 0.99 (0.68–1.46) | 0.98 | |
Acetic acid derivatives | 1142/956 | 124/78 | 0.72 (0.50–1.03) | 0.07 | |
Propionic acid derivatives | 953/781 | 313/253 | 0.78 (0.62–0.98) | 0.03 | |
cox2 inhibitors | 1250/1030 | 16/4 | - | - | |
NSAID others | 1228/1004 | 38/30 | 1.05 (0.58–1.90) | 0.86 | |
BMI <25 | NSAID (all) | 578/537 | 364/282 | 0.73 (0.57–0.94) | 0.02 |
Aspirin | 901/794 | 41/25 | 0.74 (0.40–1.35) | 0.32 | |
Acetic acid derivatives | 883/783 | 59/36 | 0.54 (0.31–0.93) | 0.03 | |
Propionic acid derivatives | 656/575 | 286/244 | 0.86 (0.66–1.13) | 0.27 | |
cox2 inhibitors | 932/816 | 10/3 | - | - | |
NSAID others | 919/806 | 23/13 | 0.98 (0.42–2.31) | 0.97 | |
BMI >25 | NSAID (all) | 592/574 | 375/343 | 0.76 (0.60–0.95) | 0.02 |
Aspirin | 906/859 | 61/58 | 1.01 (0.65–1.56) | 0.96 | |
Acetic acid derivatives | 870/837 | 97/80 | 0.81 (0.56–1.18) | 0.27 | |
Propionic acid derivatives | 694/657 | 273/260 | 0.78 (0.61–1.00) | 0.05 | |
cox2 inhibitors | 959/915 | 8/2 | - | - | |
NSAID others | 942/891 | 25/26 | 1.24 (0.64–2.41) | 0.52 |
Population | NSAID | No consumption | Consumption ≤5y | Consumption >5y | ||
---|---|---|---|---|---|---|
Controls/cases (n) | Controls/cases (n) | OR (95 % CI) | Controls/cases (n) | OR (95 % CI) | ||
All women | NSAID (all) | 1171/1111 | 484/445 | 0.81 (0.67–0.98) | 255/180 | 0.64 (0.50–0.83) |
Aspirin | 1808/1653 | 79/70 | 0.99 (0.67–1.46) | 23/13 | 0.65 (0.31–1.38) | |
Acetic acid derivatives | 1754/1620 | 113/86 | 0.75 (0.53–1.06) | 43/30 | 0.75 (0.42–1.32) | |
Propionic acid derivatives | 1351/1232 | 380/364 | 0.86 (0.71–1.06) | 179/140 | 0.73 (0.55–0.97) | |
NSAID others | 1862/1697 | 33/35 | 1.47 (0.83–2.60) | 15/4 | - | |
Premenopausal | NSAID (all) | 361/415 | 162/187 | 0.82 (0.59–1.13) | 105/100 | 0.78 (0.52–1.17) |
Aspirin | 613/689 | 12/12 | 0.72 (0.27–1.95) | 3/1 | - | |
Acetic acid derivatives | 600/664 | 21/27 | 0.68 (0.35–1.34) | 7/11 | 1.02 (0.31–3.32) | |
Propionic acid derivatives | 392/461 | 146/167 | 0.85 (0.61–1.19) | 90/84 | 0.81 (0.52–1.25) | |
NSAID others | 618/693 | 6/8 | 2.38 (0.63–9.00) | 4/1 | - | |
Postmenopausal | NSAID (all) | 805/696 | 312/258 | 0.77 (0.61–0.98) | 150/80 | 0.53 (0.38–0.75) |
Aspirin | 1181/964 | 66/58 | 1.08 (0.70–1.66) | 20/12 | 0.74 (0.33–1.65) | |
Acetic acid derivatives | 1143/956 | 88/59 | 0.76 (0.50–1.15) | 36/19 | 0.61 (0.31–1.20) | |
Propionic acid derivatives | 954/781 | 224/197 | 0.84 (0.64–1.09) | 89/56 | 0.64 (0.43–0.95) | |
NSAID others | 1229/1004 | 27/27 | 1.27 (0.66–2.42) | 11/3 | - | |
BMI <25 | NSAID (all) | 578/537 | 233/183 | 0.78 (0.58–1.04) | 131/99 | 0.65 (0.45–0.94) |
Aspirin | 901/794 | 32/22 | 0.84 (0.43–1.63) | 9/3 | - | |
Acetic acid derivatives | 883/783 | 44/22 | 0.40 (0.20–0.77) | 15/14 | 1.16 (0.42–3.15) | |
Propionic acid derivatives | 656/575 | 191/163 | 0.89 (0.66–1.21) | 95/81 | 0.80 (0.52–1.22) | |
NSAID others | 919/806 | 14/11 | 1.51 (0.56–4.06) | 9/2 | - | |
BMI >25 | NSAID (all) | 593/574 | 251/262 | 0.84 (0.65–1.08) | 124/81 | 0.61 (0.43–0.86) |
Aspirin | 907/859 | 47/48 | 1.10 (0.68–1.80) | 14/10 | 0.74 (0.30–1.82) | |
Acetic acid derivatives | 871/837 | 69/64 | 0.94 (0.61–1.44) | 28/16 | 0.54 (0.27–1.10) | |
Propionic acid derivatives | 695/657 | 189/201 | 0.85 (0.64–1.12) | 84/59 | 0.64 (0.43–0.95) | |
NSAID others | 943/891 | 19/24 | 1.44 (0.71–2.95) | 6/2 | - |
NSAID consumption and breast cancer according to tumor characteristics
Variable | Category | NSAID | Unexposed controls/cases (n) | Exposed controls/cases (n) | OR (95 % CI) | P |
---|---|---|---|---|---|---|
Clinical stage | 1–2 | NSAID (all) | 1170/696 | 739/404 | 0.80 (0.66–0.97 | 0.02 |
Aspirin | 1807/1047 | 102/52 | 0.93 (0.63–1.38) | 0.72 | ||
Acetic acid derivatives | 1753/1025 | 156/74 | 0.75 (0.54–1.06) | 0.11 | ||
Propionic acid derivatives | 1350/770 | 559/329 | 0.90 (0.74–1.11) | 0.33 | ||
cox2 inhibitors | 1891/1095 | 18/4 | - | - | ||
NSAID others | 1861/1072 | 48/27 | 1.07 (0.61–1.90) | 0.81 | ||
3–4 | NSAID (all) | 1170/136 | 739/68 | 0.74 (0.51–1.06) | 0.10 | |
Aspirin | 1807/192 | 102/12 | 1.31 (0.66–2.59) | 0.44 | ||
Acetic acid derivatives | 1753/190 | 156/14 | 0.99 (0.53–1.83) | 0.97 | ||
Propionic acid derivatives | 1350/147 | 559/57 | 0.84 (0.57–1.24) | 0.39 | ||
cox2 inhibitors | 1891/204 | 18/0 | - | - | ||
NSAID others | 1861/201 | 48/3 | - | - | ||
Pathology | Ductal cancer | NSAID (all) | 1170/835 | 739/454 | 0.70 (0.58–0.84) | <0.001 |
Aspirin | 1807/1225 | 102/64 | 0.97 (0.66–1.41) | 0.86 | ||
Acetic acid derivatives | 1753/1204 | 156/85 | 0.76 (0.55–1.06) | 0.11 | ||
Propionic acid derivatives | 1350/918 | 559/371 | 0.78 (0.64–0.95) | 0.01 | ||
cox2 inhibitors | 1891/1289 | 18/3 | - | - | ||
NSAID others | 1861/1259 | 48/30 | 1.06 (0.60–1.87) | 0.85 | ||
Non-ductal cancer | NSAID (all) | 1170/151 | 739/83 | 0.82 (0.58–1.15) | 0.25 | |
Aspirin | 1807/228 | 102/6 | 0.50 (0.21–1.19) | 0.12 | ||
Acetic acid derivatives | 1753/219 | 156/15 | 0.85 (0.46–1.58) | 0.61 | ||
Propionic acid derivatives | 1350/166 | 559/68 | 0.91 (0.63–1.31) | 0.60 | ||
cox2 inhibitors | 1891/234 | 18/0 | - | - | ||
NSAID others | 1861/232 | 48/2 | - | - | ||
Inmunohistochemistry | Hormone + | NSAID (all) | 1170/727 | 739/390 | 0.72 (0.60–0.88) | <0.001 |
Aspirin | 1807/1069 | 102/48 | 0.82 (0.55–1.24) | 0.35 | ||
Acetic acid derivatives | 1753/1044 | 156/73 | 0.76 (0.54–1.08) | 0.12 | ||
Propionic acid derivatives | 1350/805 | 559/312 | 0.80 (0.65–0.98) | 0.03 | ||
cox2 inhibitors | 1891/1115 | 18/2 | - | - | ||
NSAID others | 1861/1089 | 48/28 | 1.28 (0.73–2.25) | 0.38 | ||
HER2+ | NSAID (all) | 1170/739 | 172/83 | 0.63 (0.45–0.88) | 0.007 | |
Aspirin | 1807/102 | 244/11 | 0.79 (0.38–1.65) | 0.53 | ||
Acetic acid derivatives | 1753/238 | 156/17 | 0.67 (0.36–1.24) | 0.20 | ||
Propionic acid derivatives | 1350/188 | 559/67 | 0.66 (0.46–0.95) | 0.03 | ||
cox2 inhibitors | 1891/255 | 18/0 | - | - | ||
NSAID others | 1861/251 | 48/4 | - | - | ||
Triple negative breast cancer | NSAID (all) | 1170/94 | 739/63 | 0.87 (0.58–1.30) | 0.49 | |
Aspirin | 1807/148 | 102/9 | 1.24 (0.57–2.71) | 0.59 | ||
Acetic acid derivatives | 1753/147 | 156/10 | 0.86 (0.41–1.79) | 0.68 | ||
Propionic acid derivatives | 1350/103 | 559/54 | 0.99 (0.64–1.52) | 0.95 | ||
cox2 inhibitors | 1891/156 | 18/1 | - | - | ||
NSAID others | 1861/154 | 48/3 | - | - |
Variable | Category | NSAID | No consumption | Consumption ≤5y | Consumption >5y | ||
---|---|---|---|---|---|---|---|
Controls/cases (n) | Controls/cases (n) | OR (95 % CI) | Controls/cases (n) | OR (95 % CI) | |||
Clinical stage | 1–2 | NSAID (all) | 1171/695 | 484/281 | 0.85 (0.69–1.06) | 255/123 | 0.69 (0.52–0.92) |
Aspirin | 1808/1047 | 79/44 | 1.01 (0.65–1.58) | 23/8 | 0.74 (0.31–1.73) | ||
Acetic acid derivatives | 1754/1025 | 113/53 | 0.79 (0.53–1.17) | 43/21 | 0.73 (0.38–1.42) | ||
Propionic acid derivatives | 1351/770 | 380/234 | 0.93 (0.73–1.17) | 179/95 | 0.78 (0.57–1.08) | ||
NSAID others | 1862/1072 | 33/24 | 1.56 (0.82–2.95) | 15/3 | - | ||
3–4 | NSAID (all) | 1171/136 | 484/54 | 0.85 (0.57–1.27) | 255/14 | 0.46 (0.24–0.88) | |
Aspirin | 1808/192 | 79/11 | 1.61 (0.78–3.34) | 23/1 | - | ||
Acetic acid derivatives | 1754/190 | 113/12 | 1.08 (0.54–2.17) | 43/2 | - | ||
Propionic acid derivatives | 1351/147 | 380/45 | 0.91 (0.59–1.40) | 179/12 | 0.54 (0.27–1.09) | ||
NSAID others | 1862/201 | 33/3 | - | 15/0 | - | ||
Pathology | Ductal cancer | NSAID (all) | 1171/835 | 484/324 | 0.74 (0.60–0.91) | 255/130 | 0.60 (0.45–0.79) |
Aspirin | 1808/1225 | 79/56 | 1.09 (0.72–1.66) | 23/8 | 0.60 (0.26–1.41) | ||
Acetic acid derivatives | 1754/1204 | 113/64 | 0.78 (0.53–1.14) | 43/21 | 0.68 (0.36–1.30) | ||
Propionic acid derivatives | 1351/918 | 380/270 | 0.81 (0.65–1.02) | 179/101 | 0.68 (0.49–0.94) | ||
NSAID others | 1862/1259 | 33/28 | 1.42 (0.77–2.67) | 15/2 | |||
Non-ductal cancer | NSAID (all) | 1171/151 | 484/50 | 0.78 (0.53–1.15) | 255/33 | 0.90 (0.55–1.48) | |
Aspirin | 1808/228 | 79/5 | 0.59 (0.23–1.53) | 23/1 | - | ||
Acetic acid derivatives | 1754/219 | 113/11 | 0.92 (0.45–1.87) | 43/4 | - | ||
Propionic acid derivatives | 1351/166 | 380/40 | 0.79 (0.51–1.22) | 179/28 | 1.15 (0.67–1.96) | ||
NSAID others | 1862/232 | 33/1 | - | 15/1 | - | ||
Inmunohisto-chemistry | Hormone + | NSAID (all) | 1171/727 | 484/267 | 0.74 (0.60–0.92) | 256/123 | 0.69 (0.52–0.92) |
Aspirin | 1808/1069 | 79/38 | 0.85 (0.54–1.36) | 23/10 | 0.79 (0.36–1.75) | ||
Acetic acid derivatives | 1754/1044 | 113/50 | 0.69 (0.46–1.04) | 43/23 | 0.94 (0.51–1.75) | ||
Propionic acid derivatives | 1351/805 | 380/221 | 0.82 (0.65–1.04) | 179/91 | 0.76 (0.55–1.05) | ||
NSAID others | 1862/1089 | 33/25 | 1.62 (0.87–3.01) | 15/3 | - | ||
HER2 +/Hormone- | NSAID (all) | 1171/172 | 484/61 | 0.70 (0.48–1.01) | 255/22 | 0.49 (0.28–0.87) | |
Aspirin | 1808/244 | 79/10 | 0.89 (0.41–1.96) | 23/1 | - | ||
Acetic acid derivatives | 1754/238 | 113/16 | 1.02 (0.29–3.60) | 43/1 | - | ||
Propionic acid derivatives | 1351/188 | 380/47 | 0.66 (0.43–0.99) | 179/20 | 0.61 (0.33–1.12) | ||
NSAID others | 1862/251 | 33/4 | - | 15/0 | - | ||
Triple negative breast cancer | NSAID (all) | 1171/94 | 484/49 | 0.94 (0.60–1.48) | 255/14 | 0.60 (0.30–1.17) | |
Aspirin | 1808/148 | 79/9 | 1.74 (0.78–3.89) | 23/0 | - | ||
Acetic acid derivatives | 1754/144 | 113/8 | 0.85 (0.36–2.01) | 43/2 | - | ||
Propionic acid derivatives | 1351/103 | 380/42 | 1.04 (0.64–1.68) | 179/12 | 0.68 (0.32–1.43) | ||
NSAID others | 1862/154 | 33/2 | - | 15/1 | - |