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