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Table 3 Circulating concentrations of sRANKL 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
≤ 0.04 0.04–0.09 0.09–0.14 0.14–0.21 >  0.21
Breast cancer-specific death
All breast cancer cases
Died/total 54/421 46/443 49/374 41/363 56/369   246/1970  
HR (95% CI) Ref. 0.71 (0.47, 1.06) 0.98 (0.66, 1.45) 0.86 (0.57, 1.30) 0.99 (0.66, 1.47) 0.84 0.99 (0.92, 1.07) 0.31
OPG adjusted
HR (95% CI)c
Ref. 0.76 (0.50, 1.14) 1.05 (0.70, 1.57) 0.94 (0.61, 1.44) 1.12 (0.74, 1.71) 0.70 1.02 (0.94, 1.11) 0.43
ER+ breast cancer cases
Died/total 34/337 32/360 29/300 28/297 39/298   162/1592  
HR (95% CI) Ref. 0.84 (0.51, 1.37) 0.98 (0.59, 1.63) 0.91 (0.54, 1.51) 1.08 (0.66, 1.77) 0.81 1.01 (0.92, 1.12)  
OPG adjusted
HR (95% CI)c
Ref. 0.87 (0.53, 1.43) 1.05 (0.63, 1.74) 1.01 (0.60, 1.71) 1.24 (0.74, 2.08) 0.46 1.04 (0.94, 1.15)  
ER- breast cancer cases   
Died/total 20/84 14/83 20/74 13/66 17/71   84/378  
HR (95% CI) Ref. 0.49 (0.23, 1.02) 1.05 (0.54, 2.05) 0.77 (0.37, 1.63) 0.76 (0.37, 1.55) 0.55 0.96 (0.84, 1.10)  
OPG adjusted
HR (95% CI)c
Ref. 0.53 (0.25, 1.14) 1.14 (0.56, 2.29) 0.84 (0.39, 1.83) 0.85 (0.39, 1.86) 0.82 0.98 (0.84, 1.15)  
Death of any cause
All breast cancer cases
Died/total 103/421 91/443 73/374 68/363 79/369   414/1970  
HR (95% CI) Ref. 0.80 (0.60, 1.07) 0.79 (0.58, 1.08) 0.80 (0.58, 1.09) 0.93 (0.68, 1.27) 0.10 0.95 (0.90, 1.01) 0.20
OPG adjusted
HR (95% CI)c
Ref. 0.84 (0.63, 1.13) 0.85 (0.62, 1.16) 0.87 (0.63, 1.20) 1.04 (0.75, 1.45) 0.34 0.97 (0.91, 1.03) 0.31
ER+ breast cancer cases   
Died/total 75/337 69/360 50/300 50/297 61/298   305/1592  
HR (95% CI) Ref. 0.85 (0.61, 1.18) 0.76 (0.53, 1.10) 0.76 (0.53, 1.10) 1.00 (0.70, 1.44) 0.31 0.97 (0.90, 1.03)  
OPG adjusted
HR (95% CI)c
Ref. 0.87 (0.62, 1.22) 0.80 (0.55, 1.16) 0.84 (0.58, 1.22) 1.13 (0.78, 1.66) 0.66 0.98 (0.92, 1.06)  
ER- breast cancer cases
Died/total 28/84 22/83 23/74 18/66 18/71   109/378  
HR (95% CI) Ref. 0.62 (0.34, 1.15) 0.91 (0.50, 1.64) 0.86 (0.45, 1.61) 0.67 (0.35, 1.27) 0.11 0.91 (0.81, 1.02)  
OPG adjusted
HR (95% CI)c
Ref. 0.69 (0.36, 1.30) 0.99 (0.53, 1.86) 0.94 (0.48, 1.82) 0.76 (0.37, 1.53) 0.24 0.92 (0.81, 1.06)  
  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 sRANKL concentrations; b pheterogeneity comparing model without to model with interaction term for sRANKL and ER status using log likelihood ratio tests; c additionally adjusting for OPG concentrations (five observations missing OPG concentrations; analyses include 245 breast cancer deaths, 412 deaths of any cause)
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