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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)