Table 7.
Association of Her2 and Ki-67 expressions with survival using univariable and multivariable-adjusted Cox proportional hazards regression
| Variable | Univariable analysisa | Multivariable analysisb | ||
|---|---|---|---|---|
| HR (95% CI) | P | HR (95% CI) | P | |
| Ki-67 expression | ||||
| As continuous | 1.00 (0.99–1.01) | 0.929 | 1.00 (0.99–1.01) | 0.645 |
| − | 1 (reference) | 1 (reference) | ||
| + | 1.42 (0.67–3.03) | 0.360 | 1.15 (0.47–2.84) | 0.758 |
| ++ | 0.84 (0.41–1.74) | 0.638 | 0.73 (0.31–1.75) | 0.485 |
| +++ | 1.51 (0.66–3.46) | 0.326 | 1.46 (0.56–3.79) | 0.436 |
| Negative | 1 (reference) | 1 (reference) | ||
| Positive | 0.75 (0.49–1.14) | 0.178 | 0.76 (0.48–1.19) | 0.230 |
| Her2 expression | ||||
| − | 1 (reference) | 1 (reference) | ||
| + | 1.25 (0.73–2.14) | 0.425 | 1.04 (0.57–1.89) | 0.897 |
| ++ | 1.14 (0.64–2.03) | 0.651 | 1.27 (0.67–2.41) | 0.467 |
| +++ | 1.28 (0.66–2.48) | 0.467 | 2.17 (1.01–4.68) | 0.047 |
| Negative | 1 (reference) | 1 (reference) | ||
| Positive | 1.12 (0.71–1.76) | 0.620 | 1.52 (0.90–2.55) | 0.118 |
| Ki-67 and Her2 expression | ||||
| Her2 negative and Ki-67 negative | 1 (reference) | 1 (reference) | ||
| Her2 negative and Ki-67 positive | 0.61 (0.37–1.01) | 0.054 | 0.70 (0.41–1.20) | 0.193 |
| Her2 positive and Ki-67 negative | 0.73 (0.34–1.54) | 0.404 | 1.30 (0.56–3.01) | 0.538 |
| Her2 positive and Ki-67 positive | 0.89 (0.49–1.61) | 0.689 | 1.17 (0.60–2.29) | 0.646 |
The positivity degree of Her2 expression follows the National Comprehensive Cancer Network (NCCN) Guidelines (https://www.nccn.org): − means “no reactivity or membranous reactivity in < 10% of cancer cells”; + means “faint or barely perceptible membranous reactivity in ≥ 10% of cancer cells; cells are reactive only in part of their membrane”; ++ means “weak to moderate complete, basolateral or lateral membranous reactivity in ≥ 10% of cancer cells”; +++ means “strong complete, basolateral, or lateral membranous reactivity in ≥ 10% of cancer cells”. – or + expression indicates a negative result, and +++ expression suggests a positive finding. In case of ++ expression by immunohistochemistry, in situ hybridization was further performed, and cases with an average Her2 copy number ≥ 6.0 signals/cell are considered positive. For Ki-67, − means very low proliferation activity with proportion of Ki-67-positive cells < 25%; + means low proliferation activity with proportion of Ki-67-positive cells 25–50%; ++ means moderate proliferation activity with proportion of Ki-67-positive cells 50–75%; +++ means high proliferation activity with proportion of Ki-67-positive cells > 75%. A section was regarded negative in Ki-67 expression with < 50% positive cells, and positive with ≥ 50% positive cells. Significant associations are shown in italics
Her2 human epidermal growth factor receptor 2, HR hazard ratio, CI confidence interval
aPerformed using univariable Cox proportional hazards regression
bPerformed using multivariable Cox proportional hazards regression adjusting for sex, age, tumor location, length, differentiation grade, pT stage, and pN stage