Table 2.

Circulating concentrations of sRANKL and breast cancer risk by hormone-receptor subtype: EPIC nested case–control study

Quintiles
12345
Cut-off points (pmol/L)a<0.050.05–0.090.10–0.140.15–0.20≥0.20PtrendbRRlog2PhetcPhetd
Whole population
ER+/PR+
 Cases/controls167/198203/183176/192160/157214/190920/920
 RR (95% CI)Ref.1.31 (0.96–1.80)1.12 (0.81–1.55)1.18 (0.84–1.64)1.36 (0.99–1.87)0.311.03 (0.97–1.10)0.05
ER+
 Cases/controls339/364360/351301/327255/264343/2921,598/1,598
 RR (95% CI)Ref.1.11 (0.89–1.39)1.02 (0.80–1.29)1.03 (0.81–1.32)1.28 (1.01–1.63)0.201.03 (0.98–1.08)0.13
ER−/PR−
 Cases/controls52/5157/4047/5349/5646/51251/251
 RR (95% CI)Ref.1.54 (0.81–2.93)0.94 (0.50–1.75)0.81 (0.43–1.54)0.74 (0.39–1.38)0.080.89 (0.78–1.01)
ER−
 Cases/controls84/7983/6373/8263/8575/69378/378
 RR (95% CI)Ref.1.23 (0.74–2.03)0.75 (0.46–1.22)0.63 (0.37–1.06)0.87 (0.53–1.44)0.210.94 (0.84–1.04)
Age at diagnosis <50 years
ER+/PR+
 Cases/controls12/1227/2918/2124/1540/44121/121
 RR (95% CI)Ref.0.68 (0.21–2.24)0.56 (0.15–2.08)1.33 (0.37–4.81)0.90 (0.29–2.80)0.741.04 (0.81–1.34)
ER+
 Cases/controls16/1532/3421/2726/1848/49143/143
 RR (95% CI)Ref.0.64 (0.22–1.81)0.44 (0.14–1.43)1.00 (0.32–3.16)0.78 (0.28–2.19)0.901.02 (0.81–1.27)
Age at diagnosis ≥50 years
ER+/PR+
 Cases/controls155/186176/154158/171136/142174/146799/799
 RR (95% CI)Ref.1.38 (0.99–1.92)1.17 (0.84–1.64)1.13 (0.79–1.60)1.44 (1.02–2.03)0.331.03 (0.97–1.10)0.050.81
ER+
 Cases/controls323/349328/317280/300229/246295/2431,455/1,455
 RR (95% CI)Ref.1.13 (0.90–1.43)1.05 (0.82–1.34)1.00 (0.78–1.29)1.33 (1.03–1.70)0.221.03 (0.98–1.08)0.120.90
ER−/PR−
 Cases/controls51/4749/3441/4942/4534/42217/217
 RR (95% CI)Ref.1.51 (0.75–3.03)0.84 (0.43–1.64)0.84 (0.42–1.69)0.57 (0.28–1.13)0.060.88 (0.77–1.01)0.53
ER−
 Cases/controls79/7472/5260/7153/6855/54319/319
 RR (95% CI)Ref.1.37 (0.79–2.36)0.75 (0.45–1.25)0.70 (0.40–1.23)0.77 (0.44–1.33)0.190.93 (0.83–1.04)0.52
  • aCutpoints reflect non-log transformed sRANKL concentrations.

  • bPtrend based on log2-transformed sRANKL concentrations.

  • cPheterogeneity comparing ER+/PR+ to ER−/PR− and ER+ to ER− subtypes, based on RRlog2.

  • dPheterogeneity comparing age at diagnosis <50 to ≥50 years based on RRlog2.

  • Conditional logistic regression models adjusted for: ages at menarche (<12, 13, 14, ≥15, missing), menopause (<44, 44–47, 48–50, 51–52, 53–54, ≥55, missing), and first full-term pregnancy (no FTP, <25, 25–30, ≥30, missing), and number of full-term pregnancies (0, 1, 2, ≥3, missing) and BMI (kg/m2, continuous).