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Table 2 Circulating concentrations of OPG and risk of death following a breast cancer diagnosis, by ER subtype

From: Receptor activator of nuclear factor kB ligand, osteoprotegerin, and risk of death following a breast cancer diagnosis: results from the EPIC cohort

Cut points (pmol/L) Quintiles ptrenda HRlog2 phetb
1 2 3 4 5
≤ 7.80 7.80–9.18 9.18–10.54 10.54–12.38 >  12.38
Breast cancer-specific death
All breast cancer cases
Died/total 51/402 48/401 44/401 55/401 52/401   250/2006  
HR (95% CI) Ref. 1.04 (0.70, 1.57) 0.96 (0.63, 1.48) 1.33 (0.88, 2.00) 1.37 (0.90, 2.09) 0.13 1.30 (0.93, 1.80) 0.58
sRANKL adjusted
HR (95% CI)c
Ref. 1.08 (0.72, 1.63) 1.02 (0.66, 1.57) 1.32 (0.86, 2.01) 1.45 (0.93, 2.27) 0.12 1.32 (0.93, 1.88) 0.55
ER+ breast cancer cases
Died/total 31/318 35/321 27/322 35/328 37/331   165/1620  
HR (95% CI) Ref. 1.34 (0.81, 2.20) 1.08 (0.62, 1.85) 1.47 (0.88, 2.46) 1.77 (1.03, 3.04) 0.10 1.43 (0.94, 2.17)  
sRANKL adjusted
HR (95% CI)c
Ref. 1.44 (0.87, 2.39) 1.17 (0.67, 2.03) 1.52 (0.89, 2.59) 2.02 (1.15, 3.54) 0.07 1.52 (0.97, 2.36)  
ER- breast cancer cases
Died/total 20/84 13/80 17/79 20/73 15/70   85/386  
HR (95% CI) Ref. 0.71 (0.34, 1.51) 0.77 (0.38, 1.57) 1.27 (0.63, 2.54) 0.91 (0.44, 1.89) 0.60 1.16 (0.68, 1.99)  
sRANKL adjusted
HR (95% CI)c
Ref. 0.70 (0.32, 1.52) 0.80 (0.38, 1.68) 1.20 (0.58, 2.52) 0.86 (0.38, 1.93) 0.72 1.12 (0.62, 2.02)  
Death of any cause
All breast cancer cases
Alive/ total 77/402 71/401 71/401 93/401 109/401   421/2006  
HR (95% CI) Ref. 0.88 (0.64, 1.23) 0.83 (0.59, 1.17) 1.10 (0.80, 1.52) 1.25 (0.90, 1.73) 0.02 1.37 (1.05, 1.78) 0.66
sRANKL adjusted
HR (95% CI)c
Ref. 0.90 (0.65, 1.26) 0.83 (0.59, 1.17) 1.04 (0.75, 1.45) 1.20 (0.85, 1.69) 0.07 1.29 (0.98, 1.70) 0.66
ER+ breast cancer cases   
Died/total 53/318 54/321 47/322 71/328 84/330   310/1620  
HR (95% CI) Ref. 1.00 (0.68, 1.48) 0.83 (0.55, 1.26) 1.20 (0.82, 1.75) 1.39 (0.94, 2.05) 0.02 1.44 (1.06, 1.96)  
sRANKL adjusted
HR (95% CI)c
Ref. 1.04 (0.70, 1.54) 0.85 (0.56, 1.29) 1.17 (0.79, 1.72) 1.38 (0.92, 2.08) 0.05 1.39 (1.00, 1.92)  
ER- breast cancer cases
Died/total 24/84 17/80 24/79 22/73 24/70   111/386  
HR (95% CI) Ref. 0.70 (0.36, 1.35) 0.80 (0.43, 1.49) 1.02 (0.54, 1.93) 1.04 (0.55, 1.94) 0.34 1.27 (0.78, 2.08)  
sRANKL adjusted
HR (95% CI)c
Ref. 0.68 (0.34, 1.35) 0.74 (0.38, 1.42) 0.90 (0.46, 1.75) 0.86 (0.43, 1.32) 0.75 1.09 (0.63, 1.89)  
  1. All models adjusted for breast cancer stage (localized, non-localized, missing), BMI (kg/m2), age at blood collection (years), and age groups at menarche (≤11, 12, 13 and missing, 14, ≥15 years), menopause (premenopausal ≤ 48, 49–51, ≥52 years, missing), and first full term pregnancy (nulliparous, < 25 years, ≥25 years and missing); stratifying by age groups at diagnosis (5 year groups) and models in all cases by ER status of the tumor
  2. aptrend based on log2-transformed OPG concentrations; b pheterogeneity comparing model without to model with interaction term for OPG and ER status using log likelihood ratio tests; c additionally adjusting for sRANKL concentrations (42 observations missing sRANKL concentrations; analyses include 245 breast cancer deaths, 412 deaths of any cause)
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