Table 2. Multivariable analysis of association of CMI levels with pCR.
| a: Multivariable analysis adjusting for treatment arm and hormone receptor status (HR), by time point and by tissue and serum | ||||
|---|---|---|---|---|
| Variable | Tissue | Serum | ||
| OR (95% CI) | P-value | OR (95% CI) | P-value | |
| Baseline CMI | 0.83 (0.53, 1.30) | 0.418 | 1.1 (0.75, 1.63) | 0.615 |
| Vorinostat vs. placebo | 0.48 (0.12, 1.86) | 0.287 | 0.8 (0.23, 2.77) | 0.721 |
| HR+ vs. TNBC | 0.13 (0.03, 0.53) | 0.004 | 0.17 (0.05, 0.6) | 0.006 |
| Variable | Tissue | Serum | ||
| OR (95% CI) | P-value | OR (95% CI) | P-value | |
| D15 CMI | 0.67 (0.39, 1.13) | 0.129 | 0.85 (0.51, 1.42) | 0.542 |
| Vorinostat vs. placebo | 0.75 (0.17, 3.29) | 0.703 | 0.68 (0.19, 2.43) | 0.555 |
| HR+ vs. TNBC | 0.28 (0.06, 1.25) | 0.096 | 0.16 (0.05, 0.57) | 0.005 |
| Variable | Tissue | Serum | ||
| OR (95% CI) | P-value | OR (95% CI) | P-value | |
| CMI change from baseline | 0.57 (0.27, 1.22) | 0.147 | 0.85 (0.57, 1.27) | 0.431 |
| Vorinostat vs. placebo | 0.60 (0.13, 2.81) | 0.519 | 0.69 (0.2, 2.41) | 0.559 |
| H+ vs. TNBC | 0.26 (0.06, 1.2) | 0.084 | 0.19 (0.05, 0.66) | 0.009 |
| b: Multivariable analysis adjusting for nodal status and hormone receptor status, by time point and by tissue and serum | ||||
| Variable | Tissue | Serum | ||
| OR (95% CI) | P-value | OR (95% CI) | P-value | |
| Baseline CMI | 1.07 (0.62, 1.86) | 0.802 | 1.29 (0.83, 2) | 0.26 |
| Node + vs. - | 0.08 (0.02, 0.42) | 0.003 | 0.16 (0.04, 0.65) | 0.011 |
| HR+ vs. TNBC | 0.14 (0.03, 0.69) | 0.016 | 0.2 (0.05, 0.77) | 0.019 |
| Variable | Tissue | Serum | ||
| OR (95% CI) | P-value | OR (95% CI) | P-value | |
| D15 CMI | 0.74 (0.43, 1.27) | 0.27 | 0.87 (0.52, 1.43) | 0.575 |
| Node + vs. - | 0.15 (0.03, 0.77) | 0.023 | 0.2 (0.05, 0.74) | 0.016 |
| HR+ vs. TNBC | 0.26 (0.05, 1.31) | 0.104 | 0.2 (0.05, 0.74) | 0.016 |
| Variable | Tissue | Serum | ||
| OR (95% CI) | P-value | OR (95% CI) | P-value | |
| CMI change from baseline | 0.48 (0.22, 1.06) | 0.069 | 0.68 (0.42, 1.1) | 0.119 |
| Node + vs. - | 0.05 (0.01, 0.43) | 0.006 | 0.14 (0.03, 0.64) | 0.011 |
| HR+ vs. TNBC | 0.21 (0.03, 1.27) | 0.088 | 0.21 (0.05, 0.8) | 0.023 |
| c: Multivariable analysis adjusting for tumor stage and hormone receptor status, by time point and by tissue and serum | ||||
| Variable | Tissue | Serum | ||
| OR (95% CI) | P-value | OR (95% CI) | P-value | |
| Baseline CMI | 0.87 (0.55, 1.36) | 0.537 | 1.18 (0.8, 1.76) | 0.408 |
| Stage III vs. II | 0.52 (0.13, 2.15) | 0.368 | 0.41 (0.1, 1.72) | 0.225 |
| HR+ vs. TNBC | 0.15 (0.04, 0.59) | 0.007 | 0.18 (0.05, 0.64) | 0.008 |
| Variable | Tissue | Serum | ||
| OR (95% CI) | P-value | OR (95% CI) | P-value | |
| D15 CMI | 0.69 (0.41, 1.15) | 0.155 | 0.94 (0.57, 1.53) | 0.796 |
| Stage III vs. II | 0.75 (0.15, 3.71) | 0.725 | 0.37 (0.08, 1.61) | 0.183 |
| HR+ vs. TNBC | 0.28 (0.06, 1.28) | 0.1 | 0.18 (0.05, 0.66) | 0.009 |
| Variable | Tissue | Serum | ||
| OR (95% CI) | P-value | OR (95% CI) | P-value | |
| CMI change from baseline | 0.58 (0.28, 1.2) | 0.141 | 0.84 (0.56, 1.25) | 0.39 |
| Stage III vs. II | 0.62 (0.12, 3.16) | 0.564 | 0.36 (0.08, 1.57) | 0.173 |
| HR+ vs. TNBC | 0.25 (0.05, 1.17) | 0.079 | 0.2 (0.06, 0.73) | 0.015 |
CMI levels were natural log transformed.
Change from baseline, change of CMI defined as log (D15 CMI+1/Baseline CMI+1); CMI, cumulative methylation index; D15, 15 days after the first treatment; HR, hormone receptor PR; TNBC, triple-negative breast cancer; OR, odds ratio; CI, confidence interval;