Table 2.
Multivariable hazard ratios (HR) and 95% confidence intervals (95% CI) for breast cancer in relation to urinary levels of parent estrogens and PGE-M at baseline among postmenopausal women, with mutual adjustment
| HR (95% CI) | Parent estrogens (Estrone plus estradiol) (pg/mg Cr.) | |||||
|---|---|---|---|---|---|---|
| <680 | 680–<1132 | 1132–<1612 | 1612–<2492 | ≥2492 | p for trend | |
| Multivariable adjusted 1 | 1 | 1.47 (0.99, 2.18) | 1.02 (0.67, 1.57) | 1.22 (0.82, 1.82) | 1.57 (1.05, 2.34) | 0.139 |
| Additionally adjusted for PGE-M 2 | 1 | 1.54 (1.02, 2.31) | 1.09 (0.70, 1.70) | 1.25 (0.82, 1.90) | 1.61 (1.07, 2.42) | 0.142 |
| Estrone (pg/mg Cr.) | ||||||
| <551 | 551–<871 | 871–<1227 | 1227–<1911 | ≥1911 | p for trend | |
| Multivariable adjusted 1 | 1 | 1.10 (0.75, 1.63) | 0.88 (0.58, 1.33) | 1.13 (0.78, 1.63) | 1.30 (0.89, 1.90) | 0.183 |
| Additionally adjusted for PGE-M 2 | 1 | 1.13 (0.76, 1.69) | 0.91 (0.59, 1.39) | 1.14 (0.79, 1.66) | 1.34 (0.91, 1.97) | 0.158 |
| Estradiol (pg/mg Cr.) | ||||||
| <133 | 133–<222 | 222–<345 | 345–<589 | ≥589 | p for trend | |
| Multivariable adjusted 1 | 1 | 1.39 (0.94, 2.07) | 1.33 (0.88, 2.00) | 1.30 (0.87, 1.93) | 1.54 (1.01, 2.35) | 0.120 |
| Additionally adjusted for PGE-M 2 | 1 | 1.43 (0.95, 2.13) | 1.36 (0.90, 2.06) | 1.31 (0.87, 1.95) | 1.52 (0.99, 2.33) | 0.152 |
| PGE-M (ng/mg Cr.) | ||||||
| <3.4 | 3.4–<5.24 | 5.24–<8.34 | ≥ 8.34 | p for trend | P for interaction | |
| Multivariable adjusted 1,2 | 0.047 | |||||
| No regular use of NSAIDs | 1 | 2.16 (1.03–4.56) | 1.85 (0.90–3.81) | 2.01 (1.01–4.29) | 0.063 | |
| Regular use of NSAIDs | 1 | 0.90 (0.60–1.35) | 1.00 (0.68–1.48) | 0.99 (0.65–1.50) | 0.851 | |
| Additionally adjusted for parent estrogens 2,3 | 0.066 | |||||
| No regular use of NSAIDs | 1 | 2.14 (1.00–4.59) | 1.81 (0.86–3.81) | 2.01 (0.96–4.20) | 0.065 | |
| Regular use of NSAIDs | 1 | 0.91 (0.60–1.37) | 1.04 (0.70–1.52) | 0.99 (0.65–1.51) | 0.990 | |
| Additionally adjusted for estrone 2,3 | 0.064 | |||||
| No regular use of NSAIDs | 1 | 2.09 (0.98–4.43) | 1.80 (0.98–4.43) | 1.97 (0.95–4.11) | 0.072 | |
| Regular use of NSAIDs | 1 | 0.89 (0.59–1.34) | 1.02 (0.69–1.50) | 0.99 (0.65–1.51) | 0.990 | |
| Additionally adjusted for estradiol 2,4 | 0.055 | |||||
| No regular use of NSAIDs | 1 | 2.13 (1.01–4.48) | 1.78 (0.86–3.69) | 1.97 (0.95–4.10) | 0.108 | |
| Regular use of NSAIDs | 1 | 0.87 (0.57–1.32) | 1.00 (0.67–1.47) | 0.97 (0.63–1.49) | 0.915 | |
Models included age at enrollment (50–54; 55–59; 60–64; 65–69; 70–75y), body mass index (BMI: <25, 25–29.9, 30–34.9, or ≥ 35 kg/m2), smoking status (never, former, current), alcohol use status (never, social past; social current; regular past; regular current drinker), years of past hormone replacement therapy (HRT) use (continuous), history of breast biopsy (yes or no); and number of 1st degree family members with breast cancer (1 or ≥ 2);
Models additionally included PGE-M (<3.4; 3.4–5.24; 5.24–<8.34; ≥ 8.34), lifetime pill-years of NSAID use (<0.75 vs ≥ 0.75), and interaction terms between PGE-M and NSAID use; Models were additionally adjusted for 3 E1 levels (<551; 551–<871; 871–<1227; 1227–<1911; ≥ 1911) or 4 E2 levels (<133; 133–<222; 222–<345; 345–<589; ≥ 589).