Table 3.
Circulating concentrations of sRANKL 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 | ||||
| ≤ 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) | |
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 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)